Regenerative medicine: the ground-breaking opportunities it offers for improving patient healthcare Tuesday 8th November 2016, Jubilee Room, House of Commons Professor Andrew Webster PI - REGenableMED project

Main types of cell/tissue: Pluripotent cells hESC (allogeneic) Regenerative medicine replaces or regenerates humans cells, tissues and organs, to restore or establish normal function Main types of cell/tissue: Pluripotent cells hESC (allogeneic) “Adult” stem cells (autologous cells) Induced pluripotent cells iPSC (principally allogeneic) Said to be ‘revolutionary’ when compared to conventional treatments based on drugs or devices: it is widely claimed that RM will have the potential to provide curative treatments for a range of illnesses, such as diabetes, heart disease, and various neurological disorders

…one of the ‘Eight Great Technologies’ It has potential to treat or cure disease. Possible treatments range from a cure for diabetes to new approaches for drug screening, from curing neurological disorders to, eventually, repairing hearts. - HoL Science & Technology Committee 2013 3

Time to the clinic…the ‘translational challenge’ Translational challenges Accessibility of tissues & cells Lack of standardisation (protocols, safety criteria) Uncertainty over translational pathway Inflexible clinical trials framework Scale-up and logistical difficulties Inadequate health technology appraisal methods Potentially reluctant clinical environment Securing IP Insufficient investment from venture capital & large industry RM adoption The ‘valley of death” Time Source: Gardner and Mahalatchimy, 2015

UK Government response…reduce time taken to the clinic through: RM innovation agencies – eg Cell and Gene Therapy Catapult to enable scale-up of products for the market - £55m investment Developing schemes for accelerated review and regulation Funding major bioscience/bio-clinical research networks across UK universities, Trusts, businesses etc ATMP Taskforce reporting end of November (Chair – Ian McCubbin, GSK)

The specificity of regenerative medicine compared to other areas

Project has identified five routes to the clinic Five different pathways: Enabling, gateway innovation such as immunotherapy: e.g. gene- modified CAR T-Cells for leukaemia [Oxford Biomedica] Automated cell processing ‘point-of-care’ device/technique: e.g. the ‘Celution System’ [Cytori - Deeside] Surgeon-led innovation – e.g. the bioengineered trachea [Videregen/UCL] Implantation/infusion therapy innovation: e.g. wound/skin repair (which would not occur naturally) [Tissue Regenix - Leeds] Bioprocessing innovation - e.g. expertise and services to other parties [Cellular Therapeutics - Manchester] These are paradigmatic of the likely pathways to the clinic within regenerative medicine. They have different innovation and so adoption profiles

Need to ask how these paradigmatic cases move into the clinic – focus here on their particular ‘adoption space’ How is a new biomedical therapy/product positioned, or seen relative to existing procedures: what attributes is it given by those considering adopting it (or not) – here we move from general innovation pathways to decision-making at the clinical level…and see how the pathway becomes less clear, more messy 8

Attributed characteristics affect likely clinical adoption – some examples from our data Bioengineered trachea Autologous chondrocyte Implantation CAR T-Cells Immunotherapy Biography Plausibility Contested + ++ Distinctive/Novel Visibility - Scope Effectiveness Clinical Uncertain Cost Utility Organisational National Risks Financial Requirements Use-related -- Governance

The problem of scale-up/manufacturing of cell lines Unlike mass production of drugs, cells are live tissue, so generating (many trillions of) cells for clinical application at standard quality level is difficult: growing environment can affect the safety and potency of the material inherent variability within cell lines means that the ‘chemicals’ based concept of 100% ‘product purity’ and reproducibility may not be possible manufacturing of most RM products must take place within a clinical- grade Good Manufacturing Practice (GMP)-licensed facility. These are costly The ‘shelf life’ of this material is very limited, meaning that decentralised, distributed ‘bed-side’ closed system manufacturing models will be likely, using automated, modular, closed-system manufacturing platforms. Currently 16 such (commercial) systems being used in the UK for cell cultivation, separation and expansion

Conclusions There are quite distinct, differentiated routes to the clinic We can identify target sites/domains for helping to foster clinical adoption for different therapies Work needs to be supported related to the socio-technical and organisational structures that might be developed to reduce manufacturing costs while maintaining quality and safety. Need to envisage and prepare for Cell Therapy Centres of Excellence. Scenarios for the likely size and profiles of clinical populations treatable through different manufacturing modalities and scales should be developed to support national planning. Development of product, process and manufacturing standards and guidelines needs to be encouraged

Information on the project REGenableMED Advisory Group: Jacqueline Barry, Cell and Gene Therapy Catapult Carol Bewick, Fight For Sight Angela Blake, Pfizer Edmund Jessop, NHS England Panos Kefalas, Cell and Gene Therapy Catapult Fiona Marley, NHS England Kath Mackay, Innovate UK Robert McNabb, Cardiff University Tony Pagliuca, KCL, Clinical Lead for RM NHSE Magda Papadaki, ABPI Bernie Stocks, NHS England Mike Sullivan, Innovate UK Ahmed Syed, NHS England Website: http://www.york.ac.uk/satsu/current-projects/regenablemed/