catapult is a technology strategy board programme clinical development of cell based therapies in...
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Catapult is a Technology Strategy Board programme
Clinical development of cell based therapies in the UK
Natalie Mount PhDChief Clinical OfficerCell Therapy CatapultNov [email protected]
UK Catapults 2
Catapults are core funded by the Technology Strategy Board as ‘not for profit’ companies to bridge the gap between business, academia, research and government
Working from the science base to create new manufacturing industries for the UK
£200m+ assigned for 7 Catapults; Cell Therapy Catapult formally started in Jan 2013 and has been the only life science Catapult operating to date
Catapults use their critical mass of expertise to accelerate projects
Cell Therapy Catapult3
• Significant unmet medical needs
• Early stage in market with large potential for growth
• World class science base supported by government and charity research funders
• Development and production of cell therapies is complex
• Majority of therapies from academic researchers
Mind the (translational funding) gap 4
Catapult
• Little evidence yet that new cell therapies can be developed, licensed and adopted successfully
• Limited investment from commercial sector
• Cell Therapy Catapult partners on clinical development projects with academia, SMEs and large pharma
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Key barriers to commercialisation Pertinent issues for cell therapies
Regulatory affairs Understanding and navigating a path
Pre-clinical science Conducting the right studies to support the clinical program
Clinical development
Studying the best population; measuring the best endpoints
Manufacturing and GMP readiness Move from bench/small scale GMP process to large scale manufacture; integrating manufacturing changes with clinical data
Supply chain management
New models of delivery required; plan and test what is workable
Investment readiness Value proposition to inform potential investors
Cell therapy products need to address the industry barriers to commercialisation
Addressing Barriers6
• Economics• Health Economics• Manufacture & Supply vs Service• Business Plans
Business
• COGS & Scale up• GMP• Characterisation & Analytical• Comparability• Delivery
Manufacturing
and
Supply Chain
• Regulatory Landscape• Pre Clinical Packages• Clinical trial design• NHS partnering
Clinical
And
Regulatory
Clinical Operations & Regulatory Affairs
Process Development
Business Development
Global cell therapy industry
Established medical practice:
e.g. haematopoietic stem cell transplantation
Commercial products:
Rapidly growing global market
Global turnover of >$2bn in 2012; predicted to rise to $4-5bn in 2014; driven by diversity of small products (Apligraf, Dermagraft, Provenge made >$100m each in 2012)
Therapies licensed as ATMPs in the EU:
ChondroCelect, Glybera, MACI, Provenge
Therapies in development:
Rapidly growing ~ 250 products in clinical development
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8Overview of autologous process
From Smith, Regen Med (2012); 7 (5), 721-732
Overview of allogeneic process
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From Smith, Regen Med (2012); 7 (5), 721-732
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Marketing AuthorisationEuropean centralised licence (MAA)
(CAT) EMA
Licensed ProductClinical Trials
Clinical Trial Authorisation
National(MHRA)
EUTissues and Cells
Directiveor
Blood Directive
Transplants or Transfusions
ATMP regulation EC 1394/2007
STARTING MATERIALHuman Blood, Tissues or Cells
No
Yes
ATMP
Pre Clinical Post Marketing 30 Years Traceability
Efficacy PhV follow-up
Manufacturing Authorisation (MIA)
Manufacturing AuthorisationInvestigational
Medicinal Products (MIA(IMP))
GMP Requirement
(Eudralex Volume 4)
Substantial manipulation and/or non
homologous use
GLP
Regulation of cell therapies
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Marketing AuthorisationEuropean centralised licence (MAA)
(CAT) EMA
Licensed ProductClinical Trials
Clinical Trial Authorisation
National(MHRA in UK)
EUTissues and Cells
Directiveor
Blood Directive
Transplants or Transfusions
ATMP regulation EC 1394/2007
STARTING MATERIALHuman Blood, Tissues or Cells
No
Yes
ATMP
Pre Clinical Post Marketing 30 Years Traceability
Efficacy PhV follow-up
Manufacturing Authorisation (MIA)
Manufacturing AuthorisationInvestigational
Medicinal Products (MIA(IMP))
GMP Requirement
(Eudralex Volume 4)
Substantial manipulation and/or non
homologous use
GLP
EU Regulatory Framework
Orphan designation
Paediatric plan
Unlicensed product supply
Accelerated approval
paths
12Databases of UK preclinical (<2 yrs from clinic) and clinical stage cell therapies (April 2013)
Category Number Comparision
Preclinical (<2 yrs from clinic)
37
More allogeneic therapies in preclinical stage
Larger variety of cell types in preclinical stages
Larger range of indications for preclinical projects
Few commercially sponsored projects in both pre clinical and
clinical stages
Clinical (UK trial ongoing) 34
Total 71
http://ct.catapult.org.uk/
Bone marrow derived cells still predominate but T-cells are a rising class amongst greater diversity
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Field is growing into a broad range of disease indications
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15What’s special about cell therapy clinical trials?
Trial design aspects:
Usually administer cautiously to patients in first instance (not healthy volunteers)
Sometimes already have some non-trial patient experience (eg compassionate use)
Choosing patient population- risk:benefit assessment (early vs late stage disease, adults vs paediatrics)
Informed consent
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Trial design aspects:
Dose choice / escalation may be limited
Seamless safety and efficacy components in initial ‘transitional type’ studies can be efficient; efficacy needs to be demonstrated in adequately powered studies
Randomised, blinded, controlled clinical trials are the gold standard, but may not be suitable for some therapies:• Historical control groups
• Parallel observational groups
• Blinded assessors
• Randomised, non blinded
What’s special about cell therapy clinical trials?
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Trial conduct aspects:
Need clinician champions
Usually need long term patient follow-up (cell survival, persistence, engraftment)
Protocol deviations and amendments; ways to minimise these (dosing windows etc..)
Safety oversight and reporting
What’s special about cell therapy clinical trials?
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Trial conduct aspects:
Central importance of a very close relationship with the manufacturing team:• Logistics, logistics, logistics… (site selection, patient selection, visit
scheduling etc…)
• Clinical staff training in cell handling and administration
• Understanding route of therapy through the hospital
• Cell donation, procurement, testing, traceability, GMP, QP release
• Integrate clinical and manufacturing plans
What’s special about cell therapy clinical trials?
19Summary examples of cell therapy trial design considerations (Lunn et al., 2011)
Blood
Bone and cartilage
Cardiovascular
Dermatology/wound healing
Diabetes
Gastroenterology
Immunology
Liver
Metabolic
Neurological
Other
Ophthalmology
Respiratory
Oncology
hESC iPS MSC Immune Cell
OtherSomatic
Building the Portfolio20
Manufacturability
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• Share of expertise • Support for in house projects
• Phase 2 clinical trials• Scale up, Assays, Freezing and distribution
of cells
• Manufacturing partner, Regulatory, Clinical trial design and delivery
Large Cap Company
• Immune tolerance• Clinical development path, business models
• Regenerative tissue (cells on scaffold)Videregen; UCL, NHSBT, Royal
Free
Some project examples..
Success for the Cell Therapy Catapult means..
Leadership in building an emerging industry, addressing barriers to commercial investment
Increased numbers of cell therapies in UK trials and clinical use
Investible propositions creating successful UK companies
Demonstrating that the UK is the place to do this work
Being a leader in building a £10bn industry
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Catapult is a Technology Strategy Board programme
Industry
Cell TherapyCatapult
Investment
Researchers
NHS