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Rx.3 Cybele
Team:- Julie Harness- Geeta Chauhan- Hildegard Mack- Nick Mordwinkin- Jamieson SheffieldMentor: Antoun Nabhan
Huntington‘s: Disease in a DishWorking Toward a Cure
December 10, 2013Total interviews: 91Contact: [email protected]
Team CybeleJulie Harness, PhD Postdoctoral Fellow, UCSF Department of Neurosurgery
Stem cell biologist with background in translational research and Huntington’s Disease
Hildegard Mack, PhD Postdoctoral Fellow, UCSF Department of Biochemistry
Biochemist and cell biologist with background in basic research on aging and age-associated diseases
Geeta ChauhanDirector Innovation, Alcatel-Lucent CTO
New product development, Bell Labs Research Translation, cloud computing, data analytics, multiple startups
Nick Mordwinkin, PharmD, PhDPostdoctoral Fellow, Stanford
Stem cell biologist with background in next gen seq, drug screening, cell therapy & cardiovascular disease modeling
Deadly dominant genetic neurodegenerative disease affecting all age groups 1 in 10,000 Americans plus their families affected Aberrant gene makes mutant protein, killing Medium Spiny Neurons (MSN)
The Problem: no cure for Huntington‘s Disease
Our solution: Create affected cell type in a dish Idea: reprogram somatic cells into iPSCs and
differentiate into MSNs Starting material easily accessible Reprogramming methods established Efficient method to derive MSNs developed by us
Huntington‘s Disease (HD) at a glance
Human iPSC MSN
differentiate
One limitation on HD research/drug discovery Lack of representative animal models and cell
models Impossible to take patient samples since
affected cells are inaccessible and residing in the brain
Here is what we thought….
Cybele’s MSN can add value in a multitude of ways
Discovery Clinical DevelopmentPreclinical
Target ID & Validation
Assay Dev/ Screening
Lead Optimizatio
n
Candidate
Selection
IND Enabling
FDA App & ApprovalPh 1 Ph 2 Ph 3
First In Human
Proof of Concept
Target Hit Lead Candidate IND
Investigational New Drug
New Drug Application
NDA
Translational “valley of death”
basic research
high throughput
screen
high content screen
functional assays
2 Preclinical Phase 1 Phase 2 Phase 3 FDA App & Approval
Tool for Basic Research and Drug Discovery
Direct Therapeutic
Original Canvas Ideas
Here is what we did….
Questions to customersApproach:Q: Cells for in vitro use or direct therapeutic intervention or both?A: Therapeutic is too expensive to finance directly given the small patient population (not attractive to investors).As an in vitro tool, it might be.
Product: Q: Is it in vitro cultured cells/platform or data we generate from platform?A: Platform. Academic researchers want to control their own experiment and pharma wants to control compound libraries, experimental details and data. * But they do outsource toxicity regularly.
Customer:Q: Academic basic researchers or big pharma?A: Both, but we will focus on them at different stages of development. We also add tox screening companies and CRO’s as important players.Partnership ecosystem, licensing
Original Canvas Ideas
Here is what we found….
Universe of PartnersTools & Platforms Pharma & Biotech
NPOs
Cybele
Two products to entice licensing/partnering with cell supply companies and ADMET or pharma
Cryopreserved cell populations for direct sale
Verstile for many downstream applications
New niche product in existing market
Functional assay: Multi Electrode Array (MEA)
New product in existing market with infrastructure
Ability to determine functional response to compounds over long period of time
Ability to determine relative toxicity of compounds in MSN
* ADMET – Absorption Distribution Metabolism Excretion Toxicity
We identified several companies interested in each of our product/service options as partners, customers and/or channels
Cells for sale as research tool (off-the-
shelf and custom)
Functional assays based on
our cells
Drug candidate developed using
our cells
Color code: Channel partner Customer Partner
Competitors?
Co-development / co-ownership p
Cyprotex
Acquire technology
GSK
Cybele
Com
petitors?
Pfitzer
Provide reagents
Joint development
Velocity
Joint development
Competitors
Add to own products
CDIATCC System
Where to focus? Revenue Models Considered
Product offering # of customers Revenue per customer
Investment Required and Exit
Purified cell products
• >200• Mostly academic• Some pharma research
labs in HD
$2000 – 5000 per customer per year
~$100k(Viable)
Screening projects • 20-30• Pharma research labs w/
HD interest
$100k (pilot projects) to $1M (large-scale
screens)
~$250k(Viable)
Drug discovery w/ outlicensing of drug candidates
• 10-15• Pharma companies with
licensing / acquisition interest in HD
Potential for >$1B exit event
$50-500M(High-risk)
• Drug discovery company: Potentially worth $ billions, but requires >$50M in high-risk investment + significant capabilities added to existing MSN tech
• Cells: Relatively easy to advance to market, small revenue stream
• Screening services: Longer sales cycle than cells, but can be offered with modest investment on top of that necessary to validate cell products
Niche products in existing markets Our cell product is a „consumable“ Most similar product : neuronal Progenitor. COG = $7, sales price = $1,200 Our cells: COG = $1,500, sales price = $2,200
Top-down analysis Based on S1 of a similar company, CDI Market for „cells for in vitro drug
discovery, toxicity testing and chemical safety”
Assumes that HD share of purchases reflects HD share of NIH budget
Target market would be entire SAM
General considerations
TAM: $3.5 billion
Target Market = SAM:$8.5 million
The market for Cybele as a tools company (I)
What about a bottom-up estimate?
Bottom-up analysis Customer segments considered
• Academic reserch labs in the US: ~ 250• CROs specializing in neuronal cell toxicity: 1 validated
Products offered: Off-the-shelf cells, custom-derived cells, screening service with partner CRO
Demand will be highly variable across customers
Type of service Profit per each
Salesper year
Off-the-shelf cells $500 2,000
OR
Custom cells $10,000 100
OR
Screening service $15,000 66
Type of service Profit per each
Sales per year
total
Off-the-shelf cells $500 220 $110,000
Custom cells $10,000 10 $100,000
Screening service $15,000 2 $30,000
Total $240,000
What we can get, based on interviews
What we would need for $1 Million/year
The market for Cybele as a tools company (II)
Timeline for Cybele as a tools company2014
Q1 Q2 Q3 Q4
2015Q1 Q2 Q3 Q4
2016Q2 Q3 Q4Q1
Pro
du
cts
offe
red
De
velo
pm
en
tM
ilest
on
es
Ca
sh B
urn
(in
$1
,00
0)
Initialize Beta product Launch product development and
upscaling production New product lines
Product refinement and assay development
Pa
rtn
ers
hip
s
Research labs
CRO with expertice in ADMET analysis
Development of new products
Custom services
Cell sales
Free samples or sale of trial size
Further refinement and upscaling
-60000
-40000
-20000
0
20000
40000
60000
80000
net (revenue-costs), free samples net (revenue-costs), trial size sales
Use own cells for Drug discovery for HD, Risk mitigated due to use of hPSC Result in refine cell products, new product lines HD in NA + EY > 60,000 Onset age: 30-50 yr, 10% < 20yr, 10% > 55yr OrphanDrug status, Tax breaks, FDA fee waiver, funding...
Top-down analysis Drug Development cost ~ $100
Million Price range $50k/patient/year -
$250k/patient/year Target 50% market penetration Low End Target Market = $1.5B High End Target Market= $7.5B
General considerations
Target Market = $1.5B
The market for Cybele as a drug discovery company
TAM: $3 Billion
SAM $2.4 Billion
Drug Discovery Business Model
Biological Insight
Lead Optimization
Pre-clinical
Phase1-2a Phase 3 to Launch
Timeline 12-18 months
18 months 1 yr 2-3 yrs
Cost $10-40 Mil $5 Mil $15 Mil $40 Mil
Key Partners NCATS Assay, Screen, Chemistry groups
NCATS TRND NCATS BrIDGS
Velocity Pharmaceuticals, CROs, Big Pharma
• Skill Sets/ Capabilities: Medicinal Chemistry, HTS, PKPD, Pharmacology• Use Partners and CROs• Exit by Phase 2a• Burn Rate ~ $1-1.5 Million / month• Phase 1 ~ 50 patients, Phase 2 ~ 100 patients, Phase 3 100-400 patients• Role Model Company: Evotec
IRL1 IRL2 IRL3 IRL4 IRL5
present new data to top five customers review development plan data points final definition of pre-clinical and clinical path “proof of relevance” criteria/data/stages/quality Xtimeline to preclinical data and clinical data points X rough cost to each data point X value of program at each data point non-dilutive money sources engaged strengths/weakness compared to competition X probability and go/no go criteria at each stage X discussions with all pharma/large biotech X identify strategic need/fit at company level X present independent data specific pre-clinical and clinical path/data needed internal experts engaged X KOL discussions X Multiple pre-clinical and clinical paths identified X Independent data confirming base technology works define clinical problem the technology solves X define early data customers consider gating X define best partners (like CROs) for outsourcing X quick check on IP X external experts identified X best outsourcing for this project X additional immediate data opportunities X
Cybele on the Investment Readiness Scale
Here is what we will do next….
Next Steps1 Complete patent application.
2 Continue “bottom-up” market size analysis for cell product
3 Get back to the lab and create the data our interview partners would like to see
4 Focus on licensing partners!
Immediate Next Steps: How much will they cost?
• Acquire new undifferentated iPS line• CRISPR modify lines to contain varying repeats + control• Repeat differentiation and QC in incubator lab
Cell populationTotal Cost ~
$10,000
• Provide batch to Buck Institute for independent validation/collaboration on their phenotypic paper
• Refine protocol final stages for screening compatibility• Quantify pathology in CRISPR-modified iPS differentiated cells
• Metabolism, cell adhesion, electrophysiology, survival
Disease in a dish
Running Total Cost ~
$40,000
• Run HTS at Stanford HTBC – show cells are viable for HTS• Generate MEA array platform for high content ephys screening
Functional Assay
Running Total Cost ~
$100,000
Interested Parties: Academic labs
Interested Parties:
Interested Parties: Contact: [email protected]
Big Thanks• Teachers, Course Advisors, Mentors
• Karl Handelsman, Antoun Nabhan
• Customers and Industry KOLs who took time to do the interviews and explain us things
• UCSF, QB3, Stanford, UC Berkeley for making the Entrepreneurship resources available
• US Govt has many programs for small businesses, NIH is investing greatly for Life Sciences Research Translation
• Lots of people ready to help. All you have to do is ask, and if one shows passion and great drive people ready to line up and make your vision a reality.
Appendix
Cybele
Business Model Canvas Progression
Cybele Biologics – Original Pre Course Canvas
-Scientists creating new cellular lines,
-Intellectual Property on the diff cell lines creation process
-Consent forms for acquisition of new materials
-Internet-Direct Sales-Partner w/trusted brand and sell co-labeled product through them-StemBANCC-Regional Support Groups (eg HDSA)
Immediate:-Sales of cellular modelsLong term:-Cell-based therapy-Drug treatment mitigating/eliminating disease
IPR Licensing
Immediate:-Drug Discovery Researchers-Pharma Companies-Basic researchers-iPSC Scientists
Long term:-Patients-Medical Centers-Physicians-CMS – what health insurance co’s will reimburse
Ideal Customer now:Doing drug discovery for HD & other neurodegenerative disorders requires a stead supply of the HD Cellular Model for testing
Immediate:-Differentiated cell populations – human cellular model for HD and other genetic disorders-Drug discovery platform and tools
Reliable steady supply
Long term:-Cellular transplantation therapies-Future custom lines for personalized genomics
-Production of differentiated cellular product-Repeatable process, efficient delivery of cellular lines, batch release QC-Analytics tools for creation/ testing / validation
Production of the Cellular lines – equipment, verification, regulatory body approvals
Attracting top scientists for creation of new cellular systems
Analytics + Simulation models to speed up creation of new lines
Immediate:-People to help protect IP (lawyers etc.)
-Non-profits and advocacy groups like HDSA for the cause of finding cure for a specific genetic disorder
Long term:People to invest/help fundraise/advise/strategize
Govt; Research Universities (IRBs)Patient Advocates, Support Groups / Fund Raisers
-Research conferences (like CHDI)-Lunchtime seminars @ universities-Newsletters-Direct outreach-Social media (LinkedIn)
Cybele Biologics-Canvas version II (Week 1 Canvas)
-Scientists creating new cellular lines,
-Intellectual Property on the diff cell lines creation process
-Consent forms for acquisition of new materials
-Internet-Direct Sales-Partner w/trusted brand and sell co-labeled product through them-StemBANCC-Regional Support Groups (eg HDSA)
Immediate:-Sales of cellular modelsLong term:-Cell-based therapy-Drug treatment mitigating/eliminating disease
IPR Licensing
Academic/Industry researchers interested in basic HD biology.
Drug discovery companies with a focus on HD or neurodegenerative diseases (may be interested in expanding to HD).
Companies developing cell-based therapies (no matter for which disease, may be interested in expanding to HD)
HD Patients, their physicians, medical centers, CMS (what health insurance co’s will reimburse)
An appropriate and affordable cellular model system for basic research on HD.
An appropriate and in large quantities deliverable cellular system for drug discovery.
A direct therapeutic agent in transplantation therapies.
MVP needs to be- Highly pure- Batch-to-batch
homogeneity- QC criteria tbd- Producible in large
quantities
-Production of differentiated cellular product-Repeatable process, efficient delivery of cellular lines, batch release QC-Analytics tools for creation/ testing / validation
Production of the Cellular lines – equipment, verification, regulatory body approvals
Attracting top scientists for creation of new cellular systems
Analytics + Simulation models to speed up creation of new lines
Immediate:-People to help protect IP (lawyers etc.)
-Nn-profits and advocacy groups like HDSA for the cause of finding cure for a specific genetic disorder
Long term:People to invest/help fundraise/advise/strategize
Govt; Research Universities (IRBs)Patient Advocates, Support Groups / Fund Raisers
-Research conferences (like CHDI)-Lunchtime seminars @ universities-Newsletters-Direct outreach-Social media (LinkedIn)
Week 3 Canvas
Week 4 Canvas
Keep: Loyalty perksGrow: Custom services
Week 5 Canvas
Week 6 Canvas
Cybele Biologics -- Week 7 Canvas - Discussion
Scientists creating new cellular lines,
Intellectual Property on the diff cell lines creation process
Assay Depot/Sci Exchange
Distribution by trusted brand, like Lonza
Nonprofit research orgs like CHDI – recommend product to collaborators
Direct sales of cellular populations
Direct sales of custom differentiation jobs to CROs
IPR Licensing
CRO’s without expertise to differentiate in-house
Academics & NPOs working on HD
Pharma Companies
Tox screening companies
Physiologically relevant cell population of MSN
High purity pop. of mature MSN
High purity pop. of committed MSN progenitors
Well-char. Pop. of MSN
Well-char. populations of other human cells
Cells w/native genotype of known poly-Q length
Reduction in drug discovery costs
Reduction in tox screening costs
Production of the differentiated Cellular lines
Repeatable process, efficient delivery of cellular lines,
Analytics tools for creation/ testing / validation of cellular lines
Production of the Cellular lines – equipment, verification, regulatory body approvals
Attracting top scientists for creation of new cellular systems
Analytics + Simulation models to speed up creation of new lines
Get:Conference presenceVenture arms of pharmaSeminars in academiaRisk-free trial productKeep:Cust serv/trouble shootLoyalty programGrow:Custom services
KOL’sHDSACHDICIRM
QB3, SparkMed NCATS
CDILifetechCyprotex
Athena Health-ins co can influence pharma to use our cells
FDA - influences pharma to use our cells for tox/whatever
Stanford hospital
Whoever Dr Layzer put as contacts
Cybele Biologics -- Week 7 Canvas
Cybele Biologics -- Week 8 Canvas
