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Kevin Hrusovsky, Former CEO and President of Caliper Life Science and President of PerkinElmer's Life Sciences and Technology group will tackle the current global state of healthcare and will deliver a framework for inciting a global health revolution. He will also discuss how disruptive technologies are enabling personalized health - Cradle to Grave.
Citation preview
11 copy 2009 PerkinElmercopy 2009 PerkinElmercopy 2009 PerkinElmercopy 2009 PerkinElmer
Buckeye Growth Partners
Solect
Kevin HrusovskyManaging Director BGP Ex - Caliper CEO PerkinElmer President LSTBioForward Vision Summit
Cradle To Grave Health is Personal
22
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
33
Buckeye Growth Partners
Buckeye Growth Partners
Life Expectancy Gains are Slowing
Lifestyle is Undermining Medical Progress
First time in 200 years childrenrsquos life expectancy is shorter than parents
By 2030
1900 2000Birth Year
Life
Exp
ecta
ncy
0
10
20
30
40
50
60
70
80
90
Gains are Plateauing
Cancer kills ~8 myr ~72
Diabetes 350M double
Autism 188 57x
Asthma allergies double
44
Buckeye Growth Partners
Buckeye Growth Partners
Jaring Timmerman 100World record for backstroke
Jiroemon Kimura 115Worldrsquos Oldest Man
Buster Martin 101Marathoner Life Enthusiast
Ruth Frith 100Shot-put gold medalist
Fauja Singh 100Worldrsquos Oldest Marathon Runner
If you live to the age of a hundred you have it made because very few people die past the age of a hundredrdquo - George Burns (1896-1996)
Living Longer and Doing More
Country 100 yrs + Per 100k
China 17800 13
Canada 3795 115
UK 9330 15
France 14994 25
Japan 36376 28
USA 95548 31
55
Buckeye Growth Partners
Buckeye Growth Partners
US Healthcare Poorer Outcomes - Greater Cost
Forbes (March 2013)
$3 trillion wasted year
66
Buckeye Growth Partners
How Safe is US Healthcare
CDC (2003) NHS National Patient Safety Agency amp the Health Foundation (2008)
100000
10000
1000
100
10
11 10 100 1000 10000 100K 1M 10M
Number of encounters for each fatality
Tota
l live
s lo
st p
er y
ear
How safe is Healthcare
Driving in US
Chartered Flights
Healthcare(1 in ~600)
Dangerous(gt11000)
Ultra Safe(lt1100K)
Scheduled Commercial Airlines
European Railroads
Nuclear Power
Chemical Manufacturing
Bungee Jumping
MountainClimbing
More Dangerous than Bungee Jumping
77
Buckeye Growth Partners
Buckeye Growth PartnersldquoOne Size Fits Allrdquo Does not work $1 Trillion Wasted
Adverse drug reactions
4th leading cause of death
Toxicity
Cancer (all types) 25
Alzheimer disease 30
Hepatitis C 47
Osteoporosis 48
Diabetes 57
Asthma 60
Cardiac arrhythmias 60
Schizophrenia 60
Depression 62
0 10 20 30 40 50 60 70
Efficacy
Cost $200B yr
Depression
Schizophrenia
Cardiac arrhythmia
Asthma
Diabetes
Osteoporosis
Hepatitis C
AD
Cancer
38 cancer drugs approved 2000 - 2010Increased toxicity for targeted agents
bull GREATER MORTALITY
bull GREATER MORBIDITY
bull MORE SEVERE ADVERSE EVENTS
88
Buckeye Growth Partners
Buckeye Growth PartnersDrugsrsquo Toxic Side Effects
WarningsUsers may be at a higher risk of Ulcers Amnesia Heart Attack Stroke Enlarged breasts in
men Insomnia
Suicide
Loss of smell amp taste Internal Bleeding Birth Defects Loss of Libido Weight Gain Seizures
99
Buckeye Growth PartnersJapan is Living Longer than US
Life Expectancy
US Health in International Perspective Shorter Lives Poorer Health (2013) Correlation
Death from Noncommunicable Diseases
Life Expectancy at Birth (Men Women)
1010
Buckeye Growth Partners
Buckeye Growth PartnersCancer 1 Killer in the World and Japan
httpwwwjcancerjpenglishcancerinjapan
Japan
1111
Buckeye Growth PartnersJapan is Using Less Energy and Living Longer than US
Life Expectancy at Birth (Men Women)
US Health in International Perspective Shorter Lives Poorer Health (2013)World Bank (2011)
Energy Consumption per Capita(kg of oil equivalent per capita)
Inverse Correlation
Life Expectancy Energy Consummption
1212
Buckeye Growth Partners
Buckeye Growth PartnersJapan has one of the lowest levels of obesity
httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic
Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar
IndiaChinaJapan
South KoreaItaly
SwedenFrance
NetherlandsPoland
BrazilTurkey
FinlandGermany
RussiaSpain
GreeceIceland
South AfricaChile
CanadaBritain
AustraliaNew ZealandUnited States
Mexico
0 5 10 15 20 25 30
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
22
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
33
Buckeye Growth Partners
Buckeye Growth Partners
Life Expectancy Gains are Slowing
Lifestyle is Undermining Medical Progress
First time in 200 years childrenrsquos life expectancy is shorter than parents
By 2030
1900 2000Birth Year
Life
Exp
ecta
ncy
0
10
20
30
40
50
60
70
80
90
Gains are Plateauing
Cancer kills ~8 myr ~72
Diabetes 350M double
Autism 188 57x
Asthma allergies double
44
Buckeye Growth Partners
Buckeye Growth Partners
Jaring Timmerman 100World record for backstroke
Jiroemon Kimura 115Worldrsquos Oldest Man
Buster Martin 101Marathoner Life Enthusiast
Ruth Frith 100Shot-put gold medalist
Fauja Singh 100Worldrsquos Oldest Marathon Runner
If you live to the age of a hundred you have it made because very few people die past the age of a hundredrdquo - George Burns (1896-1996)
Living Longer and Doing More
Country 100 yrs + Per 100k
China 17800 13
Canada 3795 115
UK 9330 15
France 14994 25
Japan 36376 28
USA 95548 31
55
Buckeye Growth Partners
Buckeye Growth Partners
US Healthcare Poorer Outcomes - Greater Cost
Forbes (March 2013)
$3 trillion wasted year
66
Buckeye Growth Partners
How Safe is US Healthcare
CDC (2003) NHS National Patient Safety Agency amp the Health Foundation (2008)
100000
10000
1000
100
10
11 10 100 1000 10000 100K 1M 10M
Number of encounters for each fatality
Tota
l live
s lo
st p
er y
ear
How safe is Healthcare
Driving in US
Chartered Flights
Healthcare(1 in ~600)
Dangerous(gt11000)
Ultra Safe(lt1100K)
Scheduled Commercial Airlines
European Railroads
Nuclear Power
Chemical Manufacturing
Bungee Jumping
MountainClimbing
More Dangerous than Bungee Jumping
77
Buckeye Growth Partners
Buckeye Growth PartnersldquoOne Size Fits Allrdquo Does not work $1 Trillion Wasted
Adverse drug reactions
4th leading cause of death
Toxicity
Cancer (all types) 25
Alzheimer disease 30
Hepatitis C 47
Osteoporosis 48
Diabetes 57
Asthma 60
Cardiac arrhythmias 60
Schizophrenia 60
Depression 62
0 10 20 30 40 50 60 70
Efficacy
Cost $200B yr
Depression
Schizophrenia
Cardiac arrhythmia
Asthma
Diabetes
Osteoporosis
Hepatitis C
AD
Cancer
38 cancer drugs approved 2000 - 2010Increased toxicity for targeted agents
bull GREATER MORTALITY
bull GREATER MORBIDITY
bull MORE SEVERE ADVERSE EVENTS
88
Buckeye Growth Partners
Buckeye Growth PartnersDrugsrsquo Toxic Side Effects
WarningsUsers may be at a higher risk of Ulcers Amnesia Heart Attack Stroke Enlarged breasts in
men Insomnia
Suicide
Loss of smell amp taste Internal Bleeding Birth Defects Loss of Libido Weight Gain Seizures
99
Buckeye Growth PartnersJapan is Living Longer than US
Life Expectancy
US Health in International Perspective Shorter Lives Poorer Health (2013) Correlation
Death from Noncommunicable Diseases
Life Expectancy at Birth (Men Women)
1010
Buckeye Growth Partners
Buckeye Growth PartnersCancer 1 Killer in the World and Japan
httpwwwjcancerjpenglishcancerinjapan
Japan
1111
Buckeye Growth PartnersJapan is Using Less Energy and Living Longer than US
Life Expectancy at Birth (Men Women)
US Health in International Perspective Shorter Lives Poorer Health (2013)World Bank (2011)
Energy Consumption per Capita(kg of oil equivalent per capita)
Inverse Correlation
Life Expectancy Energy Consummption
1212
Buckeye Growth Partners
Buckeye Growth PartnersJapan has one of the lowest levels of obesity
httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic
Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar
IndiaChinaJapan
South KoreaItaly
SwedenFrance
NetherlandsPoland
BrazilTurkey
FinlandGermany
RussiaSpain
GreeceIceland
South AfricaChile
CanadaBritain
AustraliaNew ZealandUnited States
Mexico
0 5 10 15 20 25 30
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
33
Buckeye Growth Partners
Buckeye Growth Partners
Life Expectancy Gains are Slowing
Lifestyle is Undermining Medical Progress
First time in 200 years childrenrsquos life expectancy is shorter than parents
By 2030
1900 2000Birth Year
Life
Exp
ecta
ncy
0
10
20
30
40
50
60
70
80
90
Gains are Plateauing
Cancer kills ~8 myr ~72
Diabetes 350M double
Autism 188 57x
Asthma allergies double
44
Buckeye Growth Partners
Buckeye Growth Partners
Jaring Timmerman 100World record for backstroke
Jiroemon Kimura 115Worldrsquos Oldest Man
Buster Martin 101Marathoner Life Enthusiast
Ruth Frith 100Shot-put gold medalist
Fauja Singh 100Worldrsquos Oldest Marathon Runner
If you live to the age of a hundred you have it made because very few people die past the age of a hundredrdquo - George Burns (1896-1996)
Living Longer and Doing More
Country 100 yrs + Per 100k
China 17800 13
Canada 3795 115
UK 9330 15
France 14994 25
Japan 36376 28
USA 95548 31
55
Buckeye Growth Partners
Buckeye Growth Partners
US Healthcare Poorer Outcomes - Greater Cost
Forbes (March 2013)
$3 trillion wasted year
66
Buckeye Growth Partners
How Safe is US Healthcare
CDC (2003) NHS National Patient Safety Agency amp the Health Foundation (2008)
100000
10000
1000
100
10
11 10 100 1000 10000 100K 1M 10M
Number of encounters for each fatality
Tota
l live
s lo
st p
er y
ear
How safe is Healthcare
Driving in US
Chartered Flights
Healthcare(1 in ~600)
Dangerous(gt11000)
Ultra Safe(lt1100K)
Scheduled Commercial Airlines
European Railroads
Nuclear Power
Chemical Manufacturing
Bungee Jumping
MountainClimbing
More Dangerous than Bungee Jumping
77
Buckeye Growth Partners
Buckeye Growth PartnersldquoOne Size Fits Allrdquo Does not work $1 Trillion Wasted
Adverse drug reactions
4th leading cause of death
Toxicity
Cancer (all types) 25
Alzheimer disease 30
Hepatitis C 47
Osteoporosis 48
Diabetes 57
Asthma 60
Cardiac arrhythmias 60
Schizophrenia 60
Depression 62
0 10 20 30 40 50 60 70
Efficacy
Cost $200B yr
Depression
Schizophrenia
Cardiac arrhythmia
Asthma
Diabetes
Osteoporosis
Hepatitis C
AD
Cancer
38 cancer drugs approved 2000 - 2010Increased toxicity for targeted agents
bull GREATER MORTALITY
bull GREATER MORBIDITY
bull MORE SEVERE ADVERSE EVENTS
88
Buckeye Growth Partners
Buckeye Growth PartnersDrugsrsquo Toxic Side Effects
WarningsUsers may be at a higher risk of Ulcers Amnesia Heart Attack Stroke Enlarged breasts in
men Insomnia
Suicide
Loss of smell amp taste Internal Bleeding Birth Defects Loss of Libido Weight Gain Seizures
99
Buckeye Growth PartnersJapan is Living Longer than US
Life Expectancy
US Health in International Perspective Shorter Lives Poorer Health (2013) Correlation
Death from Noncommunicable Diseases
Life Expectancy at Birth (Men Women)
1010
Buckeye Growth Partners
Buckeye Growth PartnersCancer 1 Killer in the World and Japan
httpwwwjcancerjpenglishcancerinjapan
Japan
1111
Buckeye Growth PartnersJapan is Using Less Energy and Living Longer than US
Life Expectancy at Birth (Men Women)
US Health in International Perspective Shorter Lives Poorer Health (2013)World Bank (2011)
Energy Consumption per Capita(kg of oil equivalent per capita)
Inverse Correlation
Life Expectancy Energy Consummption
1212
Buckeye Growth Partners
Buckeye Growth PartnersJapan has one of the lowest levels of obesity
httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic
Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar
IndiaChinaJapan
South KoreaItaly
SwedenFrance
NetherlandsPoland
BrazilTurkey
FinlandGermany
RussiaSpain
GreeceIceland
South AfricaChile
CanadaBritain
AustraliaNew ZealandUnited States
Mexico
0 5 10 15 20 25 30
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
44
Buckeye Growth Partners
Buckeye Growth Partners
Jaring Timmerman 100World record for backstroke
Jiroemon Kimura 115Worldrsquos Oldest Man
Buster Martin 101Marathoner Life Enthusiast
Ruth Frith 100Shot-put gold medalist
Fauja Singh 100Worldrsquos Oldest Marathon Runner
If you live to the age of a hundred you have it made because very few people die past the age of a hundredrdquo - George Burns (1896-1996)
Living Longer and Doing More
Country 100 yrs + Per 100k
China 17800 13
Canada 3795 115
UK 9330 15
France 14994 25
Japan 36376 28
USA 95548 31
55
Buckeye Growth Partners
Buckeye Growth Partners
US Healthcare Poorer Outcomes - Greater Cost
Forbes (March 2013)
$3 trillion wasted year
66
Buckeye Growth Partners
How Safe is US Healthcare
CDC (2003) NHS National Patient Safety Agency amp the Health Foundation (2008)
100000
10000
1000
100
10
11 10 100 1000 10000 100K 1M 10M
Number of encounters for each fatality
Tota
l live
s lo
st p
er y
ear
How safe is Healthcare
Driving in US
Chartered Flights
Healthcare(1 in ~600)
Dangerous(gt11000)
Ultra Safe(lt1100K)
Scheduled Commercial Airlines
European Railroads
Nuclear Power
Chemical Manufacturing
Bungee Jumping
MountainClimbing
More Dangerous than Bungee Jumping
77
Buckeye Growth Partners
Buckeye Growth PartnersldquoOne Size Fits Allrdquo Does not work $1 Trillion Wasted
Adverse drug reactions
4th leading cause of death
Toxicity
Cancer (all types) 25
Alzheimer disease 30
Hepatitis C 47
Osteoporosis 48
Diabetes 57
Asthma 60
Cardiac arrhythmias 60
Schizophrenia 60
Depression 62
0 10 20 30 40 50 60 70
Efficacy
Cost $200B yr
Depression
Schizophrenia
Cardiac arrhythmia
Asthma
Diabetes
Osteoporosis
Hepatitis C
AD
Cancer
38 cancer drugs approved 2000 - 2010Increased toxicity for targeted agents
bull GREATER MORTALITY
bull GREATER MORBIDITY
bull MORE SEVERE ADVERSE EVENTS
88
Buckeye Growth Partners
Buckeye Growth PartnersDrugsrsquo Toxic Side Effects
WarningsUsers may be at a higher risk of Ulcers Amnesia Heart Attack Stroke Enlarged breasts in
men Insomnia
Suicide
Loss of smell amp taste Internal Bleeding Birth Defects Loss of Libido Weight Gain Seizures
99
Buckeye Growth PartnersJapan is Living Longer than US
Life Expectancy
US Health in International Perspective Shorter Lives Poorer Health (2013) Correlation
Death from Noncommunicable Diseases
Life Expectancy at Birth (Men Women)
1010
Buckeye Growth Partners
Buckeye Growth PartnersCancer 1 Killer in the World and Japan
httpwwwjcancerjpenglishcancerinjapan
Japan
1111
Buckeye Growth PartnersJapan is Using Less Energy and Living Longer than US
Life Expectancy at Birth (Men Women)
US Health in International Perspective Shorter Lives Poorer Health (2013)World Bank (2011)
Energy Consumption per Capita(kg of oil equivalent per capita)
Inverse Correlation
Life Expectancy Energy Consummption
1212
Buckeye Growth Partners
Buckeye Growth PartnersJapan has one of the lowest levels of obesity
httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic
Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar
IndiaChinaJapan
South KoreaItaly
SwedenFrance
NetherlandsPoland
BrazilTurkey
FinlandGermany
RussiaSpain
GreeceIceland
South AfricaChile
CanadaBritain
AustraliaNew ZealandUnited States
Mexico
0 5 10 15 20 25 30
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
55
Buckeye Growth Partners
Buckeye Growth Partners
US Healthcare Poorer Outcomes - Greater Cost
Forbes (March 2013)
$3 trillion wasted year
66
Buckeye Growth Partners
How Safe is US Healthcare
CDC (2003) NHS National Patient Safety Agency amp the Health Foundation (2008)
100000
10000
1000
100
10
11 10 100 1000 10000 100K 1M 10M
Number of encounters for each fatality
Tota
l live
s lo
st p
er y
ear
How safe is Healthcare
Driving in US
Chartered Flights
Healthcare(1 in ~600)
Dangerous(gt11000)
Ultra Safe(lt1100K)
Scheduled Commercial Airlines
European Railroads
Nuclear Power
Chemical Manufacturing
Bungee Jumping
MountainClimbing
More Dangerous than Bungee Jumping
77
Buckeye Growth Partners
Buckeye Growth PartnersldquoOne Size Fits Allrdquo Does not work $1 Trillion Wasted
Adverse drug reactions
4th leading cause of death
Toxicity
Cancer (all types) 25
Alzheimer disease 30
Hepatitis C 47
Osteoporosis 48
Diabetes 57
Asthma 60
Cardiac arrhythmias 60
Schizophrenia 60
Depression 62
0 10 20 30 40 50 60 70
Efficacy
Cost $200B yr
Depression
Schizophrenia
Cardiac arrhythmia
Asthma
Diabetes
Osteoporosis
Hepatitis C
AD
Cancer
38 cancer drugs approved 2000 - 2010Increased toxicity for targeted agents
bull GREATER MORTALITY
bull GREATER MORBIDITY
bull MORE SEVERE ADVERSE EVENTS
88
Buckeye Growth Partners
Buckeye Growth PartnersDrugsrsquo Toxic Side Effects
WarningsUsers may be at a higher risk of Ulcers Amnesia Heart Attack Stroke Enlarged breasts in
men Insomnia
Suicide
Loss of smell amp taste Internal Bleeding Birth Defects Loss of Libido Weight Gain Seizures
99
Buckeye Growth PartnersJapan is Living Longer than US
Life Expectancy
US Health in International Perspective Shorter Lives Poorer Health (2013) Correlation
Death from Noncommunicable Diseases
Life Expectancy at Birth (Men Women)
1010
Buckeye Growth Partners
Buckeye Growth PartnersCancer 1 Killer in the World and Japan
httpwwwjcancerjpenglishcancerinjapan
Japan
1111
Buckeye Growth PartnersJapan is Using Less Energy and Living Longer than US
Life Expectancy at Birth (Men Women)
US Health in International Perspective Shorter Lives Poorer Health (2013)World Bank (2011)
Energy Consumption per Capita(kg of oil equivalent per capita)
Inverse Correlation
Life Expectancy Energy Consummption
1212
Buckeye Growth Partners
Buckeye Growth PartnersJapan has one of the lowest levels of obesity
httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic
Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar
IndiaChinaJapan
South KoreaItaly
SwedenFrance
NetherlandsPoland
BrazilTurkey
FinlandGermany
RussiaSpain
GreeceIceland
South AfricaChile
CanadaBritain
AustraliaNew ZealandUnited States
Mexico
0 5 10 15 20 25 30
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
66
Buckeye Growth Partners
How Safe is US Healthcare
CDC (2003) NHS National Patient Safety Agency amp the Health Foundation (2008)
100000
10000
1000
100
10
11 10 100 1000 10000 100K 1M 10M
Number of encounters for each fatality
Tota
l live
s lo
st p
er y
ear
How safe is Healthcare
Driving in US
Chartered Flights
Healthcare(1 in ~600)
Dangerous(gt11000)
Ultra Safe(lt1100K)
Scheduled Commercial Airlines
European Railroads
Nuclear Power
Chemical Manufacturing
Bungee Jumping
MountainClimbing
More Dangerous than Bungee Jumping
77
Buckeye Growth Partners
Buckeye Growth PartnersldquoOne Size Fits Allrdquo Does not work $1 Trillion Wasted
Adverse drug reactions
4th leading cause of death
Toxicity
Cancer (all types) 25
Alzheimer disease 30
Hepatitis C 47
Osteoporosis 48
Diabetes 57
Asthma 60
Cardiac arrhythmias 60
Schizophrenia 60
Depression 62
0 10 20 30 40 50 60 70
Efficacy
Cost $200B yr
Depression
Schizophrenia
Cardiac arrhythmia
Asthma
Diabetes
Osteoporosis
Hepatitis C
AD
Cancer
38 cancer drugs approved 2000 - 2010Increased toxicity for targeted agents
bull GREATER MORTALITY
bull GREATER MORBIDITY
bull MORE SEVERE ADVERSE EVENTS
88
Buckeye Growth Partners
Buckeye Growth PartnersDrugsrsquo Toxic Side Effects
WarningsUsers may be at a higher risk of Ulcers Amnesia Heart Attack Stroke Enlarged breasts in
men Insomnia
Suicide
Loss of smell amp taste Internal Bleeding Birth Defects Loss of Libido Weight Gain Seizures
99
Buckeye Growth PartnersJapan is Living Longer than US
Life Expectancy
US Health in International Perspective Shorter Lives Poorer Health (2013) Correlation
Death from Noncommunicable Diseases
Life Expectancy at Birth (Men Women)
1010
Buckeye Growth Partners
Buckeye Growth PartnersCancer 1 Killer in the World and Japan
httpwwwjcancerjpenglishcancerinjapan
Japan
1111
Buckeye Growth PartnersJapan is Using Less Energy and Living Longer than US
Life Expectancy at Birth (Men Women)
US Health in International Perspective Shorter Lives Poorer Health (2013)World Bank (2011)
Energy Consumption per Capita(kg of oil equivalent per capita)
Inverse Correlation
Life Expectancy Energy Consummption
1212
Buckeye Growth Partners
Buckeye Growth PartnersJapan has one of the lowest levels of obesity
httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic
Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar
IndiaChinaJapan
South KoreaItaly
SwedenFrance
NetherlandsPoland
BrazilTurkey
FinlandGermany
RussiaSpain
GreeceIceland
South AfricaChile
CanadaBritain
AustraliaNew ZealandUnited States
Mexico
0 5 10 15 20 25 30
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
77
Buckeye Growth Partners
Buckeye Growth PartnersldquoOne Size Fits Allrdquo Does not work $1 Trillion Wasted
Adverse drug reactions
4th leading cause of death
Toxicity
Cancer (all types) 25
Alzheimer disease 30
Hepatitis C 47
Osteoporosis 48
Diabetes 57
Asthma 60
Cardiac arrhythmias 60
Schizophrenia 60
Depression 62
0 10 20 30 40 50 60 70
Efficacy
Cost $200B yr
Depression
Schizophrenia
Cardiac arrhythmia
Asthma
Diabetes
Osteoporosis
Hepatitis C
AD
Cancer
38 cancer drugs approved 2000 - 2010Increased toxicity for targeted agents
bull GREATER MORTALITY
bull GREATER MORBIDITY
bull MORE SEVERE ADVERSE EVENTS
88
Buckeye Growth Partners
Buckeye Growth PartnersDrugsrsquo Toxic Side Effects
WarningsUsers may be at a higher risk of Ulcers Amnesia Heart Attack Stroke Enlarged breasts in
men Insomnia
Suicide
Loss of smell amp taste Internal Bleeding Birth Defects Loss of Libido Weight Gain Seizures
99
Buckeye Growth PartnersJapan is Living Longer than US
Life Expectancy
US Health in International Perspective Shorter Lives Poorer Health (2013) Correlation
Death from Noncommunicable Diseases
Life Expectancy at Birth (Men Women)
1010
Buckeye Growth Partners
Buckeye Growth PartnersCancer 1 Killer in the World and Japan
httpwwwjcancerjpenglishcancerinjapan
Japan
1111
Buckeye Growth PartnersJapan is Using Less Energy and Living Longer than US
Life Expectancy at Birth (Men Women)
US Health in International Perspective Shorter Lives Poorer Health (2013)World Bank (2011)
Energy Consumption per Capita(kg of oil equivalent per capita)
Inverse Correlation
Life Expectancy Energy Consummption
1212
Buckeye Growth Partners
Buckeye Growth PartnersJapan has one of the lowest levels of obesity
httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic
Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar
IndiaChinaJapan
South KoreaItaly
SwedenFrance
NetherlandsPoland
BrazilTurkey
FinlandGermany
RussiaSpain
GreeceIceland
South AfricaChile
CanadaBritain
AustraliaNew ZealandUnited States
Mexico
0 5 10 15 20 25 30
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
88
Buckeye Growth Partners
Buckeye Growth PartnersDrugsrsquo Toxic Side Effects
WarningsUsers may be at a higher risk of Ulcers Amnesia Heart Attack Stroke Enlarged breasts in
men Insomnia
Suicide
Loss of smell amp taste Internal Bleeding Birth Defects Loss of Libido Weight Gain Seizures
99
Buckeye Growth PartnersJapan is Living Longer than US
Life Expectancy
US Health in International Perspective Shorter Lives Poorer Health (2013) Correlation
Death from Noncommunicable Diseases
Life Expectancy at Birth (Men Women)
1010
Buckeye Growth Partners
Buckeye Growth PartnersCancer 1 Killer in the World and Japan
httpwwwjcancerjpenglishcancerinjapan
Japan
1111
Buckeye Growth PartnersJapan is Using Less Energy and Living Longer than US
Life Expectancy at Birth (Men Women)
US Health in International Perspective Shorter Lives Poorer Health (2013)World Bank (2011)
Energy Consumption per Capita(kg of oil equivalent per capita)
Inverse Correlation
Life Expectancy Energy Consummption
1212
Buckeye Growth Partners
Buckeye Growth PartnersJapan has one of the lowest levels of obesity
httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic
Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar
IndiaChinaJapan
South KoreaItaly
SwedenFrance
NetherlandsPoland
BrazilTurkey
FinlandGermany
RussiaSpain
GreeceIceland
South AfricaChile
CanadaBritain
AustraliaNew ZealandUnited States
Mexico
0 5 10 15 20 25 30
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
99
Buckeye Growth PartnersJapan is Living Longer than US
Life Expectancy
US Health in International Perspective Shorter Lives Poorer Health (2013) Correlation
Death from Noncommunicable Diseases
Life Expectancy at Birth (Men Women)
1010
Buckeye Growth Partners
Buckeye Growth PartnersCancer 1 Killer in the World and Japan
httpwwwjcancerjpenglishcancerinjapan
Japan
1111
Buckeye Growth PartnersJapan is Using Less Energy and Living Longer than US
Life Expectancy at Birth (Men Women)
US Health in International Perspective Shorter Lives Poorer Health (2013)World Bank (2011)
Energy Consumption per Capita(kg of oil equivalent per capita)
Inverse Correlation
Life Expectancy Energy Consummption
1212
Buckeye Growth Partners
Buckeye Growth PartnersJapan has one of the lowest levels of obesity
httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic
Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar
IndiaChinaJapan
South KoreaItaly
SwedenFrance
NetherlandsPoland
BrazilTurkey
FinlandGermany
RussiaSpain
GreeceIceland
South AfricaChile
CanadaBritain
AustraliaNew ZealandUnited States
Mexico
0 5 10 15 20 25 30
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
1010
Buckeye Growth Partners
Buckeye Growth PartnersCancer 1 Killer in the World and Japan
httpwwwjcancerjpenglishcancerinjapan
Japan
1111
Buckeye Growth PartnersJapan is Using Less Energy and Living Longer than US
Life Expectancy at Birth (Men Women)
US Health in International Perspective Shorter Lives Poorer Health (2013)World Bank (2011)
Energy Consumption per Capita(kg of oil equivalent per capita)
Inverse Correlation
Life Expectancy Energy Consummption
1212
Buckeye Growth Partners
Buckeye Growth PartnersJapan has one of the lowest levels of obesity
httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic
Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar
IndiaChinaJapan
South KoreaItaly
SwedenFrance
NetherlandsPoland
BrazilTurkey
FinlandGermany
RussiaSpain
GreeceIceland
South AfricaChile
CanadaBritain
AustraliaNew ZealandUnited States
Mexico
0 5 10 15 20 25 30
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
1111
Buckeye Growth PartnersJapan is Using Less Energy and Living Longer than US
Life Expectancy at Birth (Men Women)
US Health in International Perspective Shorter Lives Poorer Health (2013)World Bank (2011)
Energy Consumption per Capita(kg of oil equivalent per capita)
Inverse Correlation
Life Expectancy Energy Consummption
1212
Buckeye Growth Partners
Buckeye Growth PartnersJapan has one of the lowest levels of obesity
httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic
Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar
IndiaChinaJapan
South KoreaItaly
SwedenFrance
NetherlandsPoland
BrazilTurkey
FinlandGermany
RussiaSpain
GreeceIceland
South AfricaChile
CanadaBritain
AustraliaNew ZealandUnited States
Mexico
0 5 10 15 20 25 30
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
1212
Buckeye Growth Partners
Buckeye Growth PartnersJapan has one of the lowest levels of obesity
httpsteadfastfinancescomblog20100923global-obesity-rates-making-money-on-the-obesity-epidemic
Japan has 8x lower rates of obesity than the USA and consumes 10x less sugar
IndiaChinaJapan
South KoreaItaly
SwedenFrance
NetherlandsPoland
BrazilTurkey
FinlandGermany
RussiaSpain
GreeceIceland
South AfricaChile
CanadaBritain
AustraliaNew ZealandUnited States
Mexico
0 5 10 15 20 25 30
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
1313
Buckeye Growth Partners
Buckeye Growth PartnersJapan Public Health Centre
Source American Journal of Clinical Nutrition (October 2012)
21 higher risk of stroke if one soft drink per day Risk of ischemic stroke 83
Strong evidence linking sweetened soft drinks to obesity cardiovascular disease diabetes and cancer
20 of USA caloric intake
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
1414
Buckeye Growth Partners
Buckeye Growth Partners23 of People are Overweight
Obesity is a global epidemic
Costs quadrupling $400B (NEJM 2005 AHRQ 2006 CBO 2008 CDC 2009)
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
1515
Buckeye Growth Partners
Buckeye Growth PartnersAchieving food addiction is a SCIENCE
70 consumed by Americans is processed food
BLISS POINT = optimal sugar fat amp salt
Use science (eg brain scans) to achieve BLISS POINT
Irony Healthy food is not profitable
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
1616
Buckeye Growth Partners
Buckeye Growth PartnersGlobally We Use More Energy and Eat Bigger Meals
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
1717
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800
1B
Growth Assaulting Ecosystems - Earth is Fighting Back
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
1818
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930
1B
2B
Growth Assaulting Ecosystems - Earth is Fighting Back
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
1919
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960
1B
2B
3B
Growth Assaulting Ecosystems - Earth is Fighting Back
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
2020
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - Earth is Fighting Back
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
2121
Buckeye Growth Partners
Buckeye Growth Partners
Earth45B years old
Life2B years old
Industrial Revolution 115959 on Dec 31
Humans150000 years old
1800 1930 1960 2011
1B
2B
3B
7B
Growth Assaulting Ecosystems - World is Fighting Back
45B years of stored fossil fuel Greenhouse gas = 400 vs 250ppm
25k species go extinctyear 80 countries no forest ndash 52k g wtree
25 trucks of waste for 1 good Super storms
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
2222
Buckeye Growth Partners
Buckeye Growth Partners
Subsidies Sugarcane
Corn
$
PricesLowered
Subsidies lead to Unintended ConsequencesBuckeye Growth Partners
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
2323
Buckeye Growth Partners
Buckeye Growth Partners
Sugarcane
Corn
Cows
Salmon
Chicken
Pesticides
Growth Hormones
Antibiotics
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
2424
Buckeye Growth Partners
Buckeye Growth Partners
Cows
Salmon
Chicken
Cancer HeartDisease
Diabetes Stroke
Over-StimulatedInsulin Growth Hormone
Omega 6 OverloadHormone Imbalance
Increased Productivity ndash Unintended Consequences on Health Buckeye Growth Partners
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
2525
Buckeye Growth Partners
Buckeye Growth Partners
69 year old truck driver Photoaging - Sun exposure
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
2626
Buckeye Growth Partners
Buckeye Growth PartnersBreast Cancer - Rising Incidence on a Global Scale
Obesity amp exerciseEarly puberty
Older pregnancies
Hormones amp Pesticides
Alcohol amp Smoking
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
2727
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
2828
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Medicine Health
INFORMATICS
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
2929
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
3030
Buckeye Growth Partners
Buckeye Growth PartnersPersonalized Health ndash Asymptomatic Medicinehellip
Source httpwwwslidesharenetjcantonfuture-of-health-care-presentation
ProbabilityOf Disease
PersonalizedMedical
Intervention
PersonalizedLifestyle
Modification
GenesBiomarkersProteomics
SNPs
EnvironmentalImpacts
Healthier
Longer Lives
Transform Sick Care into Healthcare
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
3131
Buckeye Growth Partners
Buckeye Growth Partners
GLOBAL HEALTH REVOLUTION
Extend Productive Life Economically
77 100
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
3232
Buckeye Growth Partners
Take Away Goes Here
Translating Genomics into Precision MedicineStructure of
genomesBiology of genomes
Biology of disease Advancing medicine
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Source Nature v470 p204 (2011)
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
3333
Buckeye Growth Partners
Buckeye Growth PartnersCommercial Prospects for Genomic Sequencing Technologies
Nature Reviews in Drug Discovery (May 2013)
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
3434
Buckeye Growth PartnersSuccessful Genomics ndash Marketed Drugs amp in Clinical Trials
DRUG TARGET COMPANY INDICATION STATUS
Xalkori EML4-ALK NSCLC FDA Approved in 2011
Zalboraf BRAF kinase Melanoma FDA Approved in 2011
Benlysta BLYS Lupus FDA Approved in 2011
Odanacatib Cathepsin K Osteoporosis Stopped early due to success
Atacicept BLYS Receptor Lupus PIIIII
AMG-785 Sclerostin Osteoporosis PIII
LX4211 SGLT1 Diabetes Completed PII showed POC
LX1032 TPH1 Carcinoid Syndrome Completed PII showed POC
Mapatumumab TRAIL-R1 Cancer PII
Apomab TRAIL-R2 Cancer PII
Dulanermin TRAIL Cancer PII
LX-2931 S1P Lyase Rheumatoid Arthritis PII
LX-1033 TPH1 IBS PII
OC-000459 CRTH2 R Asthma PII
DG-041 Prostanoid EPR PAD PII
Source Nat Rev Drug Disc (Jan 2011)
These drugs would not exist had it not been for genomic dataThis is the tip of the iceberg since it takes 10-15 years to develop a drug
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
3535
Buckeye Growth Partners
Buckeye Growth Partners
Propelling personalized medicine through MDx
Profound Growth of Molecular Test Scope and Availability
Source wwwgenetestsorgUpdated as of 942012
Genetic tests for 2748 diseases in 622 CLIA labs in the US
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
3636
Buckeye Growth PartnersBiomarker Tests to Improving Efficacy Safety
$2B
$4B
$5B
REQUIRES biomarker test for 26 approved drugs
RECOMMENDS biomarker test for 90 approved drugs
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
3737
Buckeye Growth Partners
ldquoA major breakthrough in metastatic melanoma treatmentrdquo NEJM Editorial August 26 2010
ldquoWe have never seen 80 response rate in melanoma This is remarkablerdquoPaul Chapman MD Memorial Sloan-Kettering Source Flaherty et al NEJM (2010)
Genomics-Enabled Breakthrough for Melanoma
81 metastatic melanoma patients with BRAF (V600E) mutation responded to treatment
Precision Medicine Breakthrough
BRAF V600 Test
BEFORE AFTER
+
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
3838
Buckeye Growth Partners
Buckeye Growth Partners
Dumb Cancers
bull Single dominant mutationbull Small mutation loadbull Monotherapy is effectivebull Resistance rare late same
pathway
Smart Cancers
bull Multiple mutational diversbull Large mutational loadbull Multi-targeted therapy requiredbull Resistance common early
Sledge G ASCO Presidential address 2011
Stupid and Smart Cancers
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
3939
Buckeye Growth Partners
Buckeye Growth Partners
Gaddy Getz Broad Institute 2011
Lung cancer has high rate of somatic point mutations
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
4040
Buckeye Growth Partners
Epigenetics
Only 20 of disease linked to germ line
mutations
Science (2010)
Diet
Drugs
Infections
Life-Style
Stress
Radiation
Pollution
Internal Chemical EnvironmentXenobiotics
InflammationPreexisting diseaseLipid peroxidationOxidative stress
Gut flora
Environment Linked to Explosion in Disease
Epidemic of Chronic Disease
Emerging as key link between environment amp NCD epidemic
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
4141
Buckeye Growth Partners
Buckeye Growth PartnersGene Expression in Monozygotic Twins
Javier and Carlos 6 years old
Anna Marie and Clotilde66 years old
Yellow = concordance
httpwwwpbsorgwgbhnovabodyepigeneticshtml
50k Person Sister amp Epi-Twin Studies70+ of Health linked to Environment
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
4242
Buckeye Growth Partners
Buckeye Growth Partners
WHO estimates 6m deaths from smoking and 06M deaths from SHS
frac14 of SHS deaths are children frac12 are women
Smoking alters methylation patterns in epigenome
20 year - 40000 patient study to examine effects of direct and second hand smoking (SHS)
One Billion Smokers Globally
Epigenetic effects of Smoking
seven automated systems
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
4343
Buckeye Growth PartnersEpigenetic changes in tumor progression
Increased Histone-modification imbalance
Increased frequency of hypermethylation
Decrease in total DNA methylation content
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
4444
Buckeye Growth Partners
Buckeye Growth Partners
Human Microbiome - ldquoThe Second Human Genomerdquo
Our bodies contain gt100x more unique bacterial genes than human genes
Asthma Atopic dermatitis
Colorectal cancer Kidney stones Periodontitis
Psoriasis
ObesityIrritable bowel disease Crohnrsquos disease
healthy micobiome perturbedhellip
Science Translational Medicine (June 2012)Trends in Genetics (January 2013)
hellipimmune and metabolic disease
ensue
Linked to Human Microbiome
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
4545
Buckeye Growth Partners
Buckeye Growth Partners
Microbiome Research is Rising Exponentially
Explosive Growth in Microbiome Research Publications since 2003
Nature Biotechnology (April 2013)
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
4646
Buckeye Growth Partners
Buckeye Growth Partners
Fact or Fallacy
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
4747
Buckeye Growth Partners
Buckeye Growth Partners
lsquoNeedingrsquo forms the
basis of addictionndash you canrsquot turn it off anymore
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
4848
Buckeye Growth Partners
Buckeye Growth PartnersFACT -- Defining food addiction
Robert LustigFood Provocateur
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
4949
Buckeye Growth Partners
Buckeye Growth Partners7 Criteria of Addiction
1
2
3
4
5
6
7
Tolerance ndash need more substance to get the same effect
Withdrawal ndash anxiety depression tremors
Bingeing
Desire or attempts to cut down or quit
Cravings or seeking
Interference with life
Use despite negative consequences
EmotionalTrigger
Guilt Craving
RitualUsing
Addiction Cycle
Addiction = 3+ of 7 criteria defined by the American Psychological Association
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
5050
Buckeye Growth Partners
Buckeye Growth PartnersThe Key Players that Determine our Metabolic Fate
DOPAMINE (neurotransmitter)
LEPTIN
hellipthe result is metabolic disease
Work well when in balance BUT when things go wronghellip
RESISTANCE
RESISTANCE
ADDICTION
INSULIN
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
5151
Buckeye Growth Partners
Buckeye Growth PartnersAll Calories
Are NOT EqualFood as a Hormone
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
5252
Buckeye Growth PartnersAll Calories are NOT Created Equal
Proteins require 10-20 times as much energy to digest as fats
Source Science (February 2013)
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
5353
Buckeye Growth Partners
Buckeye Growth PartnersA Big Mac Large French Fries amp Large Coke
The ldquotypicalrdquo fast food meal is a recipe for cardiovascular mayhem
1360 Calories Total
520 Calories from Fat
89 Daily Total Fat (58g)
89 Daily Total Cholesterol (80g)
63 Daily Total Carbohydrate (190g)
24 teaspoons of sugar (95g)
14 the fat as a block of lardhellip
hellipand 12 a cup of sugar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
5454
Buckeye Growth PartnersAll Calories are NOT Created Equal
More energy is needed to digest raw foods
Source Science (February 2013)
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
5555
Buckeye Growth PartnersCooking increases Body Mass Index
Source PNAS (Npvember 2011)
Changes in BMI on sweet potato diets
Raw Whole
Raw Pounded
Cooked Whole Cooked
Pounded
Raw
Cooked
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
5656
Buckeye Growth PartnersAll Calories are NOT Created Equal
Fruit fiber mitigates most of the negative effects of sugar
Source Science (February 2013)
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
5757
Buckeye Growth Partners
Buckeye Growth PartnersOur Craving for Sugar has Consequences
The craving for sugar has contributed to the diabetes epidemic
Analysis of 175 countries showsExtra 150 calday in sugar 11 boost in T2D
Extra 150 calday in all food01 boost in T2D
Implies sugar impacting diabetes more
than obesity
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
5858
Buckeye Growth Partners
The Mediterranean Dietthe Evidence is In
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
5959
The Mediterranean Diet ndash the Evidence is In
For the first time ever the protective effect of the Mediterranean Diet was examined in a large randomized trial
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
6060 Confidential
The Mediterranean Diet ndash the Evidence is In
7447 people with CVD risk (but no prior CVD) were split into three groups
Control Group Low Fat diet
Group 1 Mediterranean diet
PLUS given free extra virgin olive oil
Group 2 Mediterranean diet
PLUS given free nuts
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
6161
Buckeye Growth PartnersThe Mediterranean Diet ndash the Evidence is In
Control GroupLow Fat Diet
Group 1MD + Olive Oil
Group 2MD + Nuts
30 LESS LIKELY TO HAVE SUFFERED A CVD EVENT ndash AFTER 4
YEARS
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
6262
Buckeye Growth Partners
Buckeye Growth PartnersHormones Determine Our Metabolic Fate
When things are working ldquoproperlyrdquo we maintain a normal healthy weight
David on a Mediterranean Diet
Irsquom full
Leptin (adipose tissue)bull Level LOW
Dopamine (brain)bull Level LOW
Insulin (pancreas)bull Level LOW
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
6363
Buckeye Growth Partners
Buckeye Growth PartnersWhen Key Players Go Badhellip
Hormone resistance ndash and metabolic disease
David on a High Sugar and Fat Diet
Hungry amp Lazy
KeepEating
Leptin (adipose tissue)bull Level HIGH
Dopamine (brain)bull Level HIGH
Insulin (pancreas)bull Level HIGH
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
6464
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Revolutionizing amp Personalizing Global Health
1
2
3
State of Health
Personalized Health - Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
6565
Buckeye Growth Partners
Buckeye Growth PartnersFramework to Inspire Disruptive Innovation ndash Di5
Capital Transitions
Greater Purpose amp Vision
Governance amp Culture
Market Immersionamp Strategy
Innovation amp Commercialization
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
6666
Buckeye Growth Partners
Revolutionize Global Health
Innovation Asymptomatic Personalized Sustainability
United Purpose Eradicate Disease - Cancer
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
6767
Buckeye Growth Partners
Chris Maki is ALL IN
For my three little girls hellip
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
6868
Buckeye Growth Partners
Buckeye Growth Partners
Chris Allie and Tommy will never be forgottenContributed photo
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
6969
Buckeye Growth Partners
Buckeye Growth PartnersBridging The Technology Adoption Gap
Win ndash Win
Technology PatientDISEASES
TRANSLATION
Government Hospitals Pharma and Tools
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
7070
Buckeye Growth Partners
TECHNOLOGY THEMES
Imaging amp Pathology
BiomarkersMdx Cdx
Cellular Systems
Molecular Analysis
BiologicsVaccines
Targeted SmallMolecule
INFORMATICS
Personalized Health
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
7171
Buckeye Growth Partners
Buckeye Growth Partners
Need relevant predictive models
Biomarkers are enabling translation
Cancer Cardiac Stroke and Diabetes
Current industry trends
99+ attrition
$1B+ 15 years
Small AnimalCellDNA RNA Protein
HumanTissue
The Challenge Facing Our Customers
In Vitro In Vivo
TRANSLATION
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
7272
Buckeye Growth Partners
Buckeye Growth Partners
In Vitro In Vivo
Small AnimalCellDNA RNA Protein
HumanTissue
Top Challenge Facing Our Industry
TRANSLATION
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
7373
Buckeye Growth Partners
Buckeye Growth Partners
Pre-
Clin
ical
C
linic
alGoal
COST OF TESTING
DAT
A Q
UA
LITY
Disruptive Innovation
in vitro to in vivo to human
Small Animal
Cell
DNA RNA Protein
Human
Tissue
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
7474
Buckeye Growth Partners
Buckeye Growth PartnersCapturing Value through Hybrid Model
CONFIDENTIAL
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
7575 Confidential
Unification of 25 Companies
Life Sciences amp Technology
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
7676
Buckeye Growth Partners
Advances in Sequencing Technology Enable Clinical NGS
Cost Prohibitive
Cost Effective
ldquoCancer will most likely be transformed by next generation sequencingrdquo
Eric Topol The Creative Destruction of Medicine
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
7777
Buckeye Growth PartnersKey Bottlenecks in Next Generation Sequencing
Source The Global Outlook for Next Generation Sequencing Usage Platform Drivers amp Workflow (2011) BioInformatics LLCSurvey asking 267 scientists currently using Next Generation Sequencing
Sample Prep
Informatics
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
7878
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
7979
Buckeye Growth Partners
Geospiza LIMS and OmicsOffice Visualization
NGS Sample Prep Workflow Solutions
LabChip XT bull Automated DNA Fractionation and Sizing
NGS Workstation Post PCR
Isolate Sample
Fragment amp Sizing
Generate Library
Quantify Sample
Sequence Analyze
LabChip GX bull HT Bioanalyzer-like QC for DNA and RNA
NGS Workstation bull Automated High-throughput Sequencing Sample Preparation
Molecular Biology Workstation bull Nucleic Acid Extraction
MBW DS XT GX NGS XT GX NGSW Geospiza
LabChip DS bull UV-Vis DNARNA Quantification
Sequencing Service
Benefits ndash Agnostic Protocolsbull Smaller samples - Better quality bull Reduced bias - Higher throughput bull Lower costs and Informatics linkages
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
8080
Buckeye Growth PartnersCustomers Partners amp Advocates
AGBT 2012
AGBT 2011
not a comprehensive list over 500 NGS customers
AGBT 2013
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
8181
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
8282
Buckeye Growth PartnersCancer Treatment Trends at 2013 AACR
Early Detection amp Predisposition
Heterogeneity amp Resistance
Combination and Immune therapies
Non-invasive and frequent samples
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
8383
Buckeye Growth Partners
More Testing with Smaller Samples
NGS Multiplex Assays CTC Imaging
Tumor Section Core Biopsy - FNA Single Cells
More Testing
Smaller Samples
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
8484
Buckeye Growth Partners
Buckeye Growth Partners
Next Gen PathologyImperative to Embrace the Sequencing Imaging Revolution
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
8585
Buckeye Growth Partners
Buckeye Growth PartnersGenoptix Advancing Precision Medicine
AQUA avoids ~20 ER false negatives
Conventional IHCERPR ~20-40 disagr
Her2 ~20 disagrki67 no standards
Her2
ER
ki67
PR
(4 slides)
Vectra
simulated HampEDAPIERPRki67Her2all markersfind tumormeasure proteinsER+ (23)
PR-(4)
Ki67+(16)
Her2+(100)
(1 slide)
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
8686
Buckeye Growth Partners
Buckeye Growth Partnerski67 examples (4 patients w diff morphologies)
Pathology today Nearly Impossible to accurately determine of tumor cells
Error rates are 10 ndash 50
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
8787
Buckeye Growth Partners
Buckeye Growth PartnersWe add a tumor marker (red) to guide image analysis
Canrsquot be done visually Hides nuclei and weakly expressing brown stain
But ENABLED with image analysis
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
8888
Buckeye Growth Partners
Buckeye Growth PartnersinForm generates a tumor mask using pattern recognition
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
8989
Buckeye Growth Partners
Buckeye Growth PartnersIndividual tumor nuclei are scored posneg (blue neg brown pos)
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
9090
Buckeye Growth Partners
Buckeye Growth PartnersReliable automated objective accurate scores
ki67 positivity 0
ki67 positivity 64
ki67 positivity 295
ki67 positivity 80
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
9191
Buckeye Growth Partners
Buckeye Growth Partners
C
BA
D
C
A
B
High AQUALow AQUA
Ki67 Heterogeneity Quantitation
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
9292
Buckeye Growth Partners
Buckeye Growth Partners
DAPI PhalloidinKi67
KeratinSignaling 1 Signaling 2
Circulating Tumor Cells Detect 1 Cancer 1B Normal cells
MGH ChipRadiology
Takes weeks to detect
Signaling reflects drug response in days
6-color signaling assayVectra
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
9393
Buckeye Growth Partners
Buckeye Growth PartnersFluorescence-guided surgery example
Color Fluorescence Overlay
bull Nunu mouse with 4T1-luc2 tumor modelbull CatB-680 probe (2nmol100mL iv) given on day 7bull Surgery 24 hrs post injection of probebull Fluorescence imaging reveals residual tumor after primary resection
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
9494
Buckeye Growth PartnersMolecular Tools Creating Sea Change of New Applications
Food ID
Agrogenomics
Human Genomics
InfectiousDisease
Inherited Disease
Epigenomics
Transcriptomics
Cancer Diagnostics
Parental Testing
PathogenDetection
Dating
Consumer Genomics
Food and Environment
Neonatal Testing
Livestock Breeding
Fishery Mgmt
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
9595
Buckeye Growth Partners
Buckeye Growth Partners
Tests
55 available tests
Newborn screening global market opportunity
Total
130M births
North Americas
Births
4M births
$125M $750M $1B$125MMarket
Opportunity
6 2
4M births
Rest of World
122M births
Western Europe
30
100Screened 95 45
Assumes ~60 screened Average 10 testschild
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
9696
Buckeye Growth Partners
Buckeye Growth Partners
Why Autism
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
9797
Buckeye Growth Partners
Buckeye Growth PartnersAmong the last untapped Dx opportunities
Clinically important scientifically overlookedCurrent genetic tests fall shortOpportunity to leadOpportunity to change the lives of children
97
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
9898
Buckeye Growth Partners
Buckeye Growth Partners
What is Autism
98
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
9999
Buckeye Growth Partners
Buckeye Growth PartnersWhat are Autism Spectrum Disorders (ASDs)
99
Impaired Communication
Impaired Social Interactions
Repetitive Behaviors Restricted Interests
Autism Spectrum Disorders
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
100100
Buckeye Growth Partners
Buckeye Growth PartnersNo Easy Answer to ldquoWhat Causes Autismrdquo
100
5 ndash 20 Genetics bull DNA bull Single gene mutations
80 Unexplainedbull Environmentalbull Age of the fatherbull Events during pregnancybull Immune response
SynapDx Testbull Expression of genesbull Multiple sources of evidence
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
101101
Buckeye Growth Partners
Buckeye Growth PartnersThe Journey is Long amp Time Matters
101
19 months or earlier
Parentsrsquo First Concern
~45 years
Average Age of ASD Diagnosis
Get in line for Evaluation at Center
~35 years
Source wwwcdcgov wwwiancommunityorg SynapDx Parent Survey Sept 2010
486000 children suspected of developmental delay annually in US A third of patients get diagnosed at autism centers 50000 diagnosed with ASD annually Lifetime costs per ASD patient $32M
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
102102
Buckeye Growth Partners
Buckeye Growth PartnersEarly Detection Improves Outcomes
ldquo20 of children have the autism label removed when behavioral therapy is begun earlyrdquo
Geri Dawson PhD Chief Science Officer Autism Speaks Speaking at an NIH-sponsored biomarker meeting 2011
Every dollar spent on SynapDx testing could save $70
102
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
103103
Buckeye Growth Partners
Buckeye Growth Partners
80 of children with autism are missed before age three
Visit Pediatrician
Diagnosed before age 3 (2)
= Suspected of Autism Spectrum Disorder (ASD)
= Autism Spectrum Disorder Diagnosis
Missed before age 3(8)
No evaluation before age 3 Referred and evaluated by age 3
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
104104
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx test could identify 90 of children by age three
Get SynapDx Test
Missed before Age 3(1)
Diagnosed before age 3 (9)
Lower Risk test result Elevated Risk test result
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
105105
Buckeye Growth Partners
Buckeye Growth Partners
SynapDx Accelerate Time to Diagnosis
105
Autism CenterPediatricianSuspected Patient
Other Specialists Therapists
Wait until high index of suspicion
Precious Time Lost
Today
With SynapDx Test
Autism CenterPediatricianSuspected Patient
ASD Dx
ASD Dx
45 yrs old
2 yrs old
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
106106
Neonatal Diagnosis in Two Days STAT-Seq
ldquoA lot of people are going to realize that this is the futurerdquo Richard Gibbs Baylor College of Medicine
50 hours to diagnosis for $13500One test ndash 600 rare diseases
CONFIDENTIAL
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
107107
Buckeye Growth Partners
Buckeye Growth Partners
We are building ridiculously small and elegantly simple purpose-built products based on remarkable mass spectrometry technology
From security and defense to life science research and environmental monitoring bringing MS capability from the centralized lab to the point of need
Answers whenever and wherever you need them
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
108108
Buckeye Growth Partners
Buckeye Growth Partners
Centralized Model of Scientific Research
Strategic Research
Routine
Analysis
ldquoCore Facilityrdquo
Routine
Analysis
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
109109
Buckeye Growth Partners
Buckeye Growth Partners
The lsquoPersonal Mass Specrsquo Disrupts Scientific Workflows
ldquoCore Facilityrdquo
Strategic Research
Small Footprint Simple Operation Robust Adequate
Performance Affordable
Broadest Application Platform
Legacy Mass Spec
Large Size Expert Operation Maintenance Excess Performance $150K- $1M+ price
Expansive $24Bnyr Market
Biotechnology amp Medical Research
Pharmaceuticals DiagnosticsAgriculture
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
110110
Buckeye Growth Partners
Human Health Environmental Health
Side Effects
Dosage
Medicine
Symptoms
Biomarkers
Food Pathogens
Chemicals
Water Safety
Air Quality
Pollution
Exercise Nutrition
My LifePad ndash Integrating Information for Personalized Health
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
111111
Buckeye Growth Partners
Buckeye Growth Partners
N-of-Onersquos Solutions Timely Succinct Transparent Clinically actionable Non-prescriptive
N-of-Onereg Realizing Precision Medicine
12 yo M Glioblastomabull NGS identified BRAFV600E mutation more commonly
associated with melanomabull Impact Oncologist petition for vemurafenib (FDA melanoma)
25 yo F Breast Cancerbull arrayCGH detected high-level Her2 gain in recurrent tumor bull Status post mastectomy disease freebull Impact N-of-One TrialMatchTM identified Her2 vaccine trial
61 yo F Lung Cancerbull Her2neu mutation detected by DNA MassARRAY bull Impact Successful petition by oncologist for off-label use of
Herceptin patient in remission nearly 2 years
79 yo M Pancreatic bull High-level c-Met expression detectedbull Impact N-of-One TrialMatchTM identified cabozantinib trial
(FDA approved thyroid cancer)
N-of-One material confidential Do not distribute
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
112112
Buckeye Growth Partners
Buckeye Growth PartnersPKI Technology was Instrumental in these Discoveries
Pfizer Sutent (sunitinib)(kidney and stomach cancer)
Pfizer Lyrica (pregabalin)(HIV)
Pfizer Celsentri (maraviroc)(neuropathic pain)
Genentech Zelboraf (vemurafenib)(melanoma BRAF V600E mutation)
Novartis Tasigna (nilotinib)(CML chronic myeloid leukemia Gleveec resistance)
Novartis Zometa (zoledronic acid)(metastasis of breast lung prostate and multiple myeloma)
Takeda Rozerem (ramelteon)(sleep disorders)
BMS Sprycel (dasatinib)(CML chronic myeloid leukemia Gleveec resistance)
SIRTex SIR-Spheres (yttrium-90)(liver cancer)
Cubist Pharma Cubicin (daptomycin)(S aureus infections ndash MRSA treatment)
Phase I
Cell Genesys CG0070 (Bladder and multiple indications)
Nereus Pharma NPI-0052 (multiple myeloma)
Cephalon CEP-26401 (Alzheimerrsquos amp schizophrenia)
Millennium PS-341 (combo) (Non-Hodgkinrsquos Lymphoma others)
Insert Therapeutics IT101 (solid tumors)
Novartis CHIR-258 (Metastatic melanoma)
Novartis AEE788 (Advanced Cancers)
Phase IIIII
Sanofi-Aventis Aflibercept (Multiple indications)
Boehringer Ingelheim Oldodaterol (COPD)
Xencor XmAb2513 (Hodgkinrsquos Lymphoma)
Neurogen DAB-452 (Parkinson)
EntreMed Panzem (Recurrent Glioblastoma)
FDA Approved In Clinical Trials
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
113113
Buckeye Growth Partners
Buckeye Growth PartnersAgenda
Personalizing Global Health
1
2
3
State of Health
Personalized Health ndash Molecular Revolution
Inspiring Disruptive Innovation ndash Di5
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar
114114
Buckeye Growth Partners
Buckeye Growth PartnersThank You BioForward Vision Team andhellip
Dr David Rimm - YaleDr Laura Macconaill ndash Dana FarberDr Dan Haber Dr Long Le Dr Mehmet Toner ndash MGHDr Jay Flatly ndash IlluminaDr Kevin Knopp Dr Chris Petty ndash 908 DevicesDr Stan Lapedis - SynapDxDr Andrew Barry Dr Nate Cosper Dr Mark Roskey Dr Cliff Hoyt Dr Brad Rice Dr Josh Moho ndash PKI Dr Irene Rombel ndash Biotech AnalystGoogle Ventures NorthBridge Partners General Catalyst Arch Ventures
Buckeye Growth Partners
Solect Solar