1. Clinical development of cell based therapies in the UKAssociation of Research Ethics Committees Annual Conference Natalie Mount PhD Chief Clinical Officer Cell Therapy Catapult Nov 2013 natalie.mount@ct.catapult.org.ukCatapult is a Technology Strategy Board programme

2. UK Catapults Catapults are core funded by the Technology Strategy Board as not for profit companies to bridge the gap between business, academia, research and government Exploiting 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 projects2 3. 3Cell Therapy Catapult 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 4. Mind the (translational funding) gap4Little evidence yet that new cell therapies can be developed, licensed and adopted successfullyLimited investment from commercial sectorCell Therapy Catapult partners on clinical development projects with academia, SMEs and large pharmaCatapult 5. Cell therapy products need to address the industry barriers to commercialisation Key barriers to commercialisationPertinent issues for cell therapiesRegulatory affairsUnderstanding and navigating a pathPre-clinical scienceConducting the right studies to support the clinical programClinical developmentStudying the best population; measuring the best endpointsManufacturing and GMP readinessMove from bench/small scale GMP process to large scale manufacture; integrating manufacturing changes with clinical dataSupply chain managementNew models of delivery required; plan and test what is workableInvestment readinessValue proposition to inform potential investors5 6. 6Addressing Barriers Economics Health Economics Manufacture & Supply vs Service Business PlansManufacturing and Supply Chain COGS & Scale up GMP Characterisation & Analytical Comparability DeliveryClinical And Regulatory Regulatory Landscape Pre Clinical Packages Clinical trial design NHS partneringBusinessBusiness DevelopmentProcess DevelopmentClinical Operations & Regulatory Affairs 7. 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 development7 8. Overview of autologous processFrom Smith, Regen Med (2012); 7 (5), 721-7328 9. Overview of allogeneic processFrom Smith, Regen Med (2012); 7 (5), 721-7329 10. EU Tissues and Cells Directive or Blood DirectiveRegulation of cell therapiesSTARTING MATERIAL Human Blood, Tissues or CellsSubstantial manipulation and/or non homologous use YesTransplants or TransfusionsNoATMP ATMP regulation EC 1394/2007 Pre ClinicalClinical TrialsClinical Trial Authorisation National (MHRA) GMP Requirement (Eudralex Volume 4)GLPManufacturing Authorisation Investigational Medicinal Products (MIA(IMP))Licensed ProductPost Marketing 30 Years Traceability Efficacy PhV follow-upMarketing Authorisation European centralised licence (MAA) (CAT) EMAManufacturing Authorisation (MIA)10 11. EU Tissues and Cells Directive or Blood Directive11STARTING MATERIAL Human Blood, Tissues or CellsSubstantial manipulation and/or non homologous use YesEU Regulatory Framework Transplants or TransfusionsNoATMP ATMP regulation EC 1394/2007 Pre ClinicalGMP Requirement (Eudralex Volume 4)GLPUnlicensed Clinical Trials product Post Marketing Licensed Product 30 Years Traceability supply PaediatricEfficacy PhV follow-up plan Orphan Clinical Trial Marketing Authorisation designation Authorisation European centralised licence (MAA) Accelerated National (CAT) EMA approval (MHRA in UK) paths Manufacturing Authorisation Investigational Medicinal Products (MIA(IMP))Manufacturing Authorisation (MIA) 12. Databases of UK preclinical (