Business-led Translation A presentation by CEO, Keith Thompson, about growing a UK cell therapy industry. Oct 2013

1. Business-led Translation
Growing a UK cell therapy industry
delivering
health and wealth
Keith Thompson CEO
Terrapin
Stem Cell, Cord Blood and Cell Culture Conference,
Cambridge MA.
October 2nd 2013
info@ct.catapult.org.uk
Catapult is a Technology Strategy Board programme

2. The Launch of Catapults
Hauser Report
• Creating new manufacturing industries for the UK
• Better exploiting the UK science base
• “Grow and stick”
Technology Strategy Board
• £440m for innovation in 2013/14
• £250m+ assigned to TSB for 7 Catapults 2012
•
High Value Manufacturing, Cell Therapy, Offshore Renewables, CDE, Satellite
Applications, Transport Systems, future Cities
• 2 new ones announced August 2013
•
Stratified Diagnostics, Energy Storage
• Mandated to bridge the gap between research and
commercialisation through industry collaboration
2

3. Cell Therapy
-Mind the (translational funding) gap
3
•
Limited evidence yet that new cell
therapies can be developed, licensed and
adopted successfully
•
Limited commercial investment
•
Limited precedents for valuable exits via
IPO or acquisition
•
Large corporates mostly watching and
waiting
•
Operational SME’s lack finance and
breadth of resources for rapid advance
Catapult

4. Industry Barriers
Business
Manufacturing
and
Supply Chain
Clinical
And
Regulatory
• Health Economics
• Business Models
• Reimbursement
• Partnering
• Robustness & Reliability
• COGS & Scale up
• Characterisation & Analytical
• GMP
• CMC
• Delivery
• Complex Regulatory Landscape
• Pre Clinical Packages
• Clinical trial design
• NHS partnering
4

5. Approach
Project led
• Pathfind therapies into and through the Clinic and
out and into the market
Ø Core projects with direct investment
Ø Rounded phase II data package
Ø Investible propositions
• Assist industry to progress to commercialisation
Ø Collaboration
Ø Contract research
• Technology platforms
Ø Develop novel technologies and license to industry
• Train professionals though immersion
5

6. Stage Gated
6
Proof of Principle
• Scientific, clinical, regulatory, commercial
Non-clinical
• Safety, toxicology, GMP proving, assays
Suitability
• Commercial
Development
Plan
Clinical
• Safety and efficacy, investible data
Platform
• Generic issues and large collaborations

7. Projects: Successful Path to Commercialisation
7
Regulatory agency dialogue on
plans at each stage
-start with the end product in mind and deliver an integrated plan
Science
•
•
Efficacy and safety hypothesis and evidence
Definition and characterisation of cellular product
Clinical
•
•
•
•
Patient population, unmet medical need, differentiation
Safety
Robust evidence of efficacy
Dose and dosing regimen
•
•
•
GMP manufacturing process; release; comparability assays
Supply logistics
Scale-up / scale –out; Control of cost
•
•
•
Pricing and reimbursement plan
Defensibility (IP, know-how…)
Commercialisation partner
Manufacturing
Business

8. Working models and finance
8
Nature of project Paid for by: Carried out by:
Ownership
of outputs
Finance
Core Project
Catapult
Catapult
Catapult
£70m/
5 years
Contracted
Development
Client
Catapult
Client
£10m/
Per year
Industry
Collaboration
Grant or
Catapult
Catapult
and
and partner partner
Outputs
shared
£10m/
Per year

9. Funding for Cell Therapy in the UK
Govt.
Support
Medical
Charities
Commercial
Development
Plan
Financial
Investment
Corporate
Venturing
9

10. Assets
10
-Facilities and Teams
Facilities
•
•
•
•
Central London location
1200 sq m on 12th floor Guys Tower
Clinical research cluster
Capacity for 100 people
Teams
• Business
•
•
Business development
Business models
•
Health economics
• Manufacturing and Supply
•
Process development
•
Analytical development
•
•
GMP process proving
Supply Chain
• Clinical Trial and Regulatory
•
•
•
Regulatory
Clinical trial sponsor
Clinical operations

11. Manufacturing and Supply Chain Development
Catapult is a Technology Strategy Board programme
11

12. Lab - Pilot - Scale
12
Catapult Multi Functional development Pod
Commercial Scale
Catapult GMP Proving Lab
T
e
c
h
t
r
a
n
s
f
e
r

13. Product release criteria
Non clinical
development
Phase I
13
Phase II
Market
Approval
Phase III
•
Cell therapy characterisation requirements change depending upon where a
product is in the commercialisation process
•
Goal is to define and quantify the critical quality attributes for a particular
product (release criteria)
•
Need to develop appropriate assays for product release which can be
incorporated into the manufacturing process (rapid, simple)
Pilot GMP
Process
Development
Process
Commercial
Process
Scale Up/
Out

14. Cell therapy characterisation
Non clinical
development
Phase I
Phase II
14
Phase III
Market
Approval
Products in pre-clinical development often require more thorough/complex
characterisation using more advanced analytical approaches to understand the product
MOA
Cell markers
Potential
potency markers
Identification
markers
Direct Surrogate
Purity assay
process qualification
Pilot GMP
Process
Process Comparability
Development
Process
Commercial
Process
Scale Up/
Out

15. Cell therapy characterisation
Non clinical
development
Phase I
Phase II
15
Phase III
Market
Approval
MOA
Cell markers
Raw Materials
Stability
Potential
potency markers
Identification
markers
Direct Surrogate
Purity assay
Sterility testing
Mycoplasma
Virus testing
Endotoxins
Shelf life
Genetic stability
Viability
the aim is to develop assays that are reliable, reproducible with low variance,
Pilot GMP
Commercial
Scale Up/
Development
inexpensive, simple, andProcess with appropriate reference standards — that
rapid,
Process
Process
Out
also have relevance to the intended clinical activity.

16. Health Economics
Catapult is a Technology Strategy Board programme

17. For healthcare products, price, reimbursement and
demand are interlinked determinants of profit
All these have to be effectively addressed to reach
commercial goals…
PRICE
PROFIT
REIMBURSEMENT
17
DEMAND

18. Successful commercialization depends on both
regulatory approval and optimal market access
Quality
Safety
Efficacy
REGULATORY APPROVAL
18
Comparative Clinical & CostEffectiveness; Budget Impact
MARKET ACCESS

19. Payers have a common aim: to achieve the greatest
health care value for the money they spend
Payers are key market access decision-makers
(with input from clinical and economic advisors)
Is it
worth it?
Does it add
value
over SOC?
Cost-effectiveness
Price comparison
Can we
afford it?
Budget impact
Should we
control
its use?
Comparative
clinical
effectiveness
Restrictions
Do we need
to fund it?
Is the product
needed?
Unmet need
Political imperative
The emphasis on these elements differs
across markets, most notably the use of
cost-effectiveness in decision-making
19

20. Pricing approaches in healthcare are shifting
towards value-based models
Cost-based
Competitor-based
Value-based
What is it?
• Price is set by
assumptions on
costs, expected
sales volumes and
margins
• Price is driven by
the pricing of
competitor
products
• Price is based
upon
therapeutic /
economic value to
the customer
Examples
• Cost-plus pricing
• ROI based pricing
(e.g. PPRS in UK)
• Penetration
pricing
• Reference group
pricing
• Value-based
pricing
Comments
20
• Enforced by many
reimbursement
• Becoming obsolete;
no longer resonates
systems for
“undifferentiated”
with payers
products
• Typical approach
for differentiated
products

21. Value-based pricing relies on the quantification of the
added-value that a new technology delivers over SOC
• Reference Value of Standard of Care (SOC)
o Comparative data against the SOC is required:
V = RV + PDV - NDV
H2H comparative data demonstrating superiority or
non-inferiority of Product X against the SOC is preferred
Ø Indirect comparisons of high methodological standards
(NMA) sufficient for non-inferiority claims
Ø
PDV
Negative
Differentiation
Value (NDV)
Positive
Differentiation
Value
V
RV
21
Reference
Value (SOC)
NDV
• Differentiating Value
o Clinical effectiveness
o Economic impact: budget impact, cost-minimization,
cost-effectiveness, cost-utility
• Value (V)
o For a given indication “V” varies depending on the
intervention’s positioning in the treatment algorithm
& the target patient profile

22. In markets like UK, cost-effectiveness is the measure of
value and the determinant of reimbursed price
• QALYs are the measure of clinical effectiveness
Ø QALYs = Life expectancy (life years) x Quality of life (utility)
Ø
Ø
•
Utility ranges from 0 (death) to 1 (full health)
Utility determined by HRQoL instruments; incorporation in clinical trials is key for market access
Costs
Ø
Direct (healthcare) and indirect (social care) costs
o
Incremental Cost Effectiveness Ratio (ICER)
Ø
QoL (utility score)
•
Societal costs (e.g. time off work) not yet accounted by NICE
22
1.0
Cost B-Cost A / QALY B- QUALY A
NICE ICER thresholds:
• Set at £20K/QALY; up to £30K justifiable
if:
Treatment A
Ø
Treatment B
0.5
Ø
•
QALYs gained (B vs A)
•
Orphans: No defined threshold
Under VBP additional factors are likely to
impact ICER threshold e.g.
Ø
0
1
Life Years
There is confidence in results
Technology is highly innovative
Ø
Ø
Disease burden
Level of unmet need
Size of target population

23. Main commercial preparations to optimize market access
Enviromental
Reviews
Qualitative
Research with Key
Market Access
Stakeholders
Suitability assessment
• Assess
• Generate insights
opportunity (e.g. on reaction to
epidemiology,
“Target Product
disease burden,
Profile”, key value
unmet need,
drivers, likely
Objectives clinical /pricing
positioning,
benchmarks,
pricing,
funding &
reimbursement,
supporting data
uptake,
requirements,
supporting data
competition)
requirements
23
Value Story
Development
Development
Quantitative
Pricing
Research
Value Dossier
Development
Out-licensing or Launch
• Development of • Identify revenue
clinical value
maximising
arguments and
target price
economic models • Inform asset
• Test value story
valuation and
with key market
market access
access
strategy
stakeholders
• Enhance market
• Identify areas to
strengthen story
and data
access potential
and strategic
partnering
• Compile in a
single document
clinical and
economic value
proposition and
corresponding
evidence to
support
negotiations

24. Clinical Trials
Catapult is a Technology Strategy Board programme
24

25. Databases of UK preclinical (<2 yrs from clinic)
and clinical stage cell therapies
Category
Preclinical (<2 yrs from
clinic)
Number
Comparision
More allogeneic therapies in
preclinical stage
37
Larger variety of cell types in
preclinical stages
Larger range of indications for
preclinical projects
Clinical (UK trial ongoing)
34
Total
71
http://ct.catapult.org.uk/
Few commercially sponsored
projects in both pre clinical and
clinical stages
25

26. Regulation………
• Interact with regulators to improve
clarity and speed
• Clinical access to NHS
• Clinical Trial Sponsor
• Use the existing flexibility
26

27. Clinical trials for cell therapies
27
Safety
•
•
•
Risk mitigation
Monitoring
Duration follow-up
Efficacy
•
Patient population
•
•
•
Risk vs benefit
Disease stage
Paediatrics
Logistics
•
Very close integration of
clinical and
manufacturing teams
Dose selection
•
•
Recognised
endpoints
• Head to head
comparison
• HRQoL
Placebo and
blinding
• In study vs
• historical /parallel
Single vs multiple
Dose escalation
Feasibility
•
•
Accompanying
device / surgical
technique
Manufacturing success
rate

28. Project Examples
Catapult is a Technology Strategy Board programme
28

29. Identifying projects
• Pre-clinical and clinical databases
• Technology transfer offices
• Intermediaries
• Grant Funders
• Industry Groups
• Charities
• Investors
• Direct contact
•
•
Inward investors
EU entrants

30. Collaborations
30
• Cooperation on
manufacturing
platforms
• Project sourcing and
funding
• International
collaboration

31. Project Examples
• Share of expertise
• Support for in house projects
• New delivery device to reduce injection
pain
• Phase 2 clinical trials
• Scale up, Assays, Freezing and distribution
of cells
Large Cap
Company
• Manufacturing partner, Regulatory,
Clinical trial design and delivery
• Immunomodulation
• Regulatory, Clinical trial design, business
models
31

32. Platform Project Example
-Build a GMP iPS bank with Roslin Cells
Biopsy
Reprogramming
Existing registry
of volunteers
for platelet and
BM donation
Known subpopulation of
triple HLA-A, B
and DR
homozygotes
Cell therapy
GMP iPS cell bank
Differentiated cells/
tissues of chosen
types and origins
Phase 1: Generate 6 cell lines: £2m
•
•
Generate highly specified Master and Working Cell banks
Generate Research grade equivalents and distribute to bona fide researcher
Phase 2: Expand to 20 cell lines: £3m
• Milestone and success driven
Phase 3: Expand to 100 cell lines:
• Self financing dependent upon early clinical trial results

33. INVESTABILITY
Market
sen-ment
for
cell
therapy
investments
improving
• Looking
for
rounded
data
package
Clinical
Data,
Health
Economics,
Business
Models,
Market
Access,
Reimbursement,
Defensibility
• Pricing
target
and
COGS
drive
long
term
margin
towards
valuaHon
• Clinical
Data
incorporaHng
H2H
and
HRQoL
improves
valuaHon
Health
economics,
pricing
and
value
story
built
to
support
commercialisaHon
Transac-ons
• Financial
investment
–
Venture
Capital
• Corporate
Venturing
• Direct
Corporate
TransacHons

34. Strategic Goals
Pipeline
• Increased cell therapies in UK clinical trial and clinical use
Value
• Investible propositions created leading to cell therapy companies
that succeed and stay in the UK
Attractiveness
• Demonstrating that the UK is the place to do this work, with
increased inward investment
Goals
• Build a £10bn industry
34

35. Researchers
Industry
Cell Therapy
Catapult
NHS
info@ct.catapult.org.uk
www.celltherapycatapult.org.uk
Catapult is a Technology Strategy Board programme
Investment