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The Era Of Genomic Medicine…
What to expect
Ronnie Andrews
President, Medical Sciences
The Medical Diagnostics World Begins & Ends With a
Patient/Physician Encounter
Therapy Selection
Prognosis Diagnosis Screening
Biopsy
Primary Care / Specialists Pathology Oncology Pr imary Care / Oncology
Morphology
H&E IHC Fish Pathology Data
Bioformational
Synthesis
Physician
Dashboard
Cells
Selected
Recurrence Monitoring
Therapy Monitoring
Sample
Prep Genomic
Analysis qPCR
Confirmation
Can We Expect History to Repeat Itself?
Clinical
Chemistry
1970
1980
1990
1990
Microbiology
1970
1980
1990
1995
Immuno
Chemistry
1980
1985
1990
1990
Automated
Blood
Banking
1990
1995
2000
2005
Molecular
Dx
1998
2000
2005
TBD
NGS
2012
TBD
As complexity of disease is better understood, and Therapeutic
Monitoring of Targeted Rx becomes a reality, the race to
democratize NGS will increase.
Translational Medicine Today When all else has failed and outcome is binary…
• Genomic information is identifying intervention points for treatment
• Off label attempts to save the patient are emerging
• Successes based on “pathway treatment approach” are becoming more prevalent
Understanding Variation and Its Link to Disease or Response
Evolving Model Driven By Therapeutic Availability
A Collision Course with Complexity
• 500 compounds on the way
• Targeting more than 100 biomarkers
• $6 million & 2 years to develop each
• Multiple Dx tests for each marker
Today’s Model is Unsustainable
Hospital
Reference Lab
Esoteric Lab
Pharma (CRO)
Sample
1
Cost - $1,000
Days - 5
Cost - $2,500
Days - 5
Cost - $4,000
Days - 15
Cost - $0
Days - 15
Sample 2
Sample
3
Sample
4 “Where do I go for
what test and
what do I do with
the information?”
Total Cost ~$7,500
Patient Health
Total Days 40
The Promise of Next Generation Sequencing
Sequencing-Guided Medicine Optimal Therapy Selection
PTEN+
KRAS-
• Profile hundreds of genes at once
• Price comparable to individual Dx tests
• Fast turnaround time
• Easily incorporate new genes as clinical
science advances
Anatomic
Classification
Genomic
Classification
Moore’s Law
$3B
$5K
1999 2011 2005
Cost to
sequence
genome
Clinical
Value
Co
st
Pe
r G
en
om
e In
form
atio
n V
alu
e
Pathologist’s Opportunity…Information Synthesis
Real Time Access To Comparative Information
Becomes Pathologist’s Tool
GCI Software
GCI Data
System
Interpreting physician
Variants
Treating physician
Knowledge apps Treatment
& Outcomes
Health
Info:
Treatment
& Outcomes
Sequence Data
Genomic data
Page 11
Single service order:
1) Tissue profiling (multiplex staining)
2) NGS Exome – Genome performed (variants,
expression profile, structural variation, epigenetics)
3) Utilize informatics tools to query against knowledge
base
4) Follow Rules-Based Treatment guidelines to select
treatment (combination cocktail) based on marker
pattern
CT screen /PET
scan identifies
suspicious lung
mass
Doctor
receives
treatment
guidance
Personalized
treatment
prescribed
Doctor Orders Molecular
Medicine 2.0 Services
!
Tissue biopsy
performed
Evidence Based Informatics Will Allow Maturation
of Clinical Care
How One Man Sees The Future…
Page 12
Deeper understanding of biological pathways drives confidence
in treatment recommendations
Growing number of patients benefiting from diagnostics that
repurpose existing and emerging therapies in combination with
standard of care
Access to targeted population-based medicine supports patient-
centric decisions through more targeted therapeutic
interventions
Less invasive monitoring – personalized, using Individual
Molecular Signatures (IMS)
Molecular Medicine 1.0 (0- 3 Years) (New Biomarkers Driving Biological Interpretation)
Molecular Medicine 2.0 (3-5 Years) (Rules-Based Approaches to Individualized Treatment)
The Initial Offering From Path Labs
Targeted
Molecular
Analysis
Panels based
on actionability
(RUO device)
Variant List,
Protein
Profiles
Database
query:
Pathway
correlation
Pertinent
Perturbed
Pathways
List
Database
query: Drug/
pathway
interactions
Patient
sees her
oncologist,
gets new
tumor
biopsy
Treatment
Options
Therapy
Options:
Combinations,
Side effects,
PGx, Cost, etc.
Confirmation
of Variants as
a basis of
intervention
(CLIA/ FDA
Device)
Treatment
Preference
Treatment
Prescribed
Patient’s response entered into database to
further refine gene-to-treatment algorithm for
other patients
Page 13
!
Expert
Intermediary
“Molecular
Physician”
Aspirational Care Model 4-7 years
Page 14
Molecular Medicine 3.0
(Rules-based treatment)
Patient now understands how her cancer is different and her
physician is making personalized decisions to help manage her
chronic disease
Molecular data from multiple biomarker types has been integrated
to inform patient options
Many more targeted drugs are available, with selection supported
by “rules” established in smaller targeted clinical studies
Real Time query of annotated database allows for comparative
medicine approach to ensure the best treatment protocol specific to
the patient
Individual Molecular Signatures (IMS) developed at diagnosis
Personalized, less invasive disease monitoring
Wellness metric
H&E
Molecular Pathologist :
Specimen procurement
Tissue Processing
Embedding / Cutting / Cover Slipping
Laser Capture
Microdissection
Future integrator of molecular interrogation of tissue
Tissue Prep for Molecular Sequencing
Integrated Pathology Workstation
(Digital path to enable data integration with
molecular)
IHC
PGM
Slides
Tissue
SS
ISH
Today’s AP Lab
Future AP Lab
Phenotypic analysis
Genotypic analysis
Medical database
Experiential database
Tissue Prep and Primary
Staining Primary
Staining
Advanced Staining Microscope
Digital Path
Synthesis Engines Will Allow For Critical Queries
1. Which
alterations are
seen in similar
patients as
mine?
Treating
Physician
Patient Clinical
Information • Role-based workflow
and user interface
• Interpretation of routine
assays
• Interface w/
Annotated/Curated
databases and
analytical tools
• Reporting
• Security, audit,
archive…
Ion Reporter
Interpreting
Physician
2. Which are likely
drivers vs.
passenger
mutations in my
patient?
3. Are the driver
mutations for my
patient pointing to
specific actionable
targets?
4. What is the
clinical evidence
for response to
the specific
targets I am
considering for
my patient?
Torrent Suite
Sequencer
Sequence
Exomes
Genomes
Variants
Report
A
B A
B
EGFR Pathway Disrupted
The Interpreting Physician Cockpit
7 GE Title or job number
7/13/2011
The Plan
• Drive Patient-focused
decisions – Treating your
disease, not a disease
• Convergence and integration
of Life Science and Dx
technologies
• Develop Bioinformatics to
attach lifelong health data to
patient and deliver
comprehensive patient
information for better
decision making
• Capitalize on the exponential
expansion of the Molecular
Diagnostics market
12 GE Title or job number
7/13/2011
Key Segment: Molecular Diagnostics
Precise therapy
requires precise
diagnostics
The way we look at disease is changing Assembling the necessary technologies
to lead
Responders
Patient populations
Mammography Molecular Biopsy Tools
Tumor
+
IHC Stain
Gene sequencing Molecular pathology
Imaging Molecular Diagnostics
Alzheimer’s Disease Age matched control
[18F]AH110690 PET Imaging
90 –120 min summation
Alzheimer’s Disease Age matched control
[18F]AH110690 PET Imaging
90 –120 min summation
Operations &
commercialization
Molecular imaging
agents & equipment
Technology &
content
Enabling
workflow
in vivo
diagnostics
GRC
Molecular
Pathology
Digital
Pathology
Clarient
Molecular profiling segment for cancer expected to
grow from $15B in 2010 to $47B in 2015
... to be a leader in the next diagnostic
frontier
Toxic
impact
No
impact
Driving toward a patient-centric, technology-agnostic vision of the future requires
use of multiple biomarker types, access to comparative medicine database and
clinical judgment
The Treating Physician Portal
• Allows real time access to patient
information and education to drive
better management of complex
diseases
Decentralizing NGS Empowers Community Practitioners
• Practice research medicine
• Create content
• Validate utility
• Drive standard of care
• Research flexibility
• Non-regulated OK
• Bio-Informatic solutions w/
flexible algorithms
• Fast followers
• Assertive/Competitive
• Want to "Look Like" 1%
• Sophisticated workforce
• Regulated needs
• Fixed algorithms
• Support Local community with high
level of care
• Center of Excellence for monitoring
• Automated
• Sophisticated workflows
• Fixed algorithms
• High level tech support
• Advanced informatics & reporting
• IVD Requirement
Attributes System Needs <200
<500
>2,000
>3,000
Democratization Of NGS Will Happen
Clinical
Chemistry
1970
1980
1990
1990
Microbiology
1970
1980
1990
1995
Immuno
Chemistry
1980
1985
1990
1990
Automated
Blood
Banking
1990
1995
2000
2005
Molecular
Dx
1998
2000
2005
TBD
NGS
2012
Large and Medium Sized Hospital Labs Should Begin
Preparation to Become Molecular Labs and Embrace Their Role
in Bringing Personalized Medicine to the Community!
2020
2014
2015
Semiconductors Disrupt Industries
21
Transformative Technology, Unprecedented Progress Scalable Semiconductor Technology plus Simple Chemistry
Wafer Semiconductor Manufacturing
Chip Semiconductor Packaging
Millions of Sensors Semiconductor Design
Sensor Plate
Silicon Substrate
Drain Source Bulk
∆ pH
∆ V
Sensing Layer
H+
Single Sensor Chemical to Digital Sequence
TCGTACC…
Ion Semiconductor Sequencing Rapid, bench top sequencing for all
23 The content provided herein may relate to products that have not
been officially released and is subject to change without notice.
Headwinds To Success
• Access to archived patient cohorts
• Increased Regulatory Oversight/Complexity
• Lack of understanding on how to effectively
reimburse for MolDx
• Payors resisting paying for therapeutics “off label”
• Technology ease of use
• No focused didactic training around molecular
pathology (need “Interpreting Physician”)
Our Call To Action
• Embrace the change…a chance to elevate
laboratory medicine to an integral function in
disease management
• Let your voice count…become active in industry
associations to educate and promote the
acceptance of MolDx by payors and regulators
• Focus on the Patient…the next 10 years
represent a major tipping point for solving complex
diseases
Far and away the best prize that life offers is
the chance to work hard at work worth doing
Theodore Roosevelt
Q&A