Regenerative medicine: boutique products within a resource limited NHS and how to develop and deliver them Tuesday 8th November 2016, Jubilee Room, House of Commons Professor Antonio Pagliuca National Clinical Lead RM NHSE King’s College London

UK Industry growth 2012 to 2015 $500m+ 42 +90% +1,000 +50% +70% Investment 2015 ¹Investment attracted by UK companies in 2015 vs. $54m in 2012 42 +90% ATMP therapy developers 50% are rapidly growing Growth in the number of ATMP therapy companies since 2012 +1,000 +50% +70% Jobs created are up from 540 in 2012 (expected to exceed 2,000 in 5yrs) Growth in UK clinical trials since 2012 GMP footprint 22 facilities/11,800m². A 70% increase vs. 2013 ¹Excludes Smith & Nephew acquisition of Healthpoint for $782M in 2012

Who are the actors Cell and Gene Therapy Catapult NHSBT/SBTS NHS/AHSC/Universities Spin Outs SME Pharma Big Pharma

Cell and Gene Therapy -Translational gap Government spending skewed to early stage research Catapult funding in translational Gap Catapult

The typical pathway

Study areas in Cell and Gene Therapy/Regenerative Medicine Neurological Cancer Tissue repair Eye Cellular and Gene Therapy Other

CAR T cell Therapy – Phase 1 study. Cellectis/Servier/Pfizer (UCART19) May obviate the complex autologous CAR-T processes KHP Universal CAR T Cell (UCART19) pRL-123-28-csp9SIN CAR123-28-csp9 PGK prom CAR-123/33 CD28 2A iCaspase9 KHP CAR T Cell against CD123/CD33 2nd generation intracellular CAR signaling domains – CD28 and CD3 Self-inactivating lentiviral vector backbone First Universal Chimeric Antigen Receptor T cell (UCART19) in Adult patient in the UK (Paeds at GOSH/ICH) T cell Activation Adoption of CAR TALEN- gene editing Cell Expansion & Infusion TARGETED THERAPY Third Party Donor

Gene Therapy for Haemoglobinopathies Thalassemia and Sickle Cell Disease Autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human beta-A-T87Q globin gene Will open in limited centres across Europe – one or two centres in the UK Requires myeloablation HGB-206 - LentiGlobin BB305 is Bluebird bio's first trial to enrol just patients with severe sickle cell disease

Athersys: MUST-ARDS trial Aim: To carry out a Phase 1/2 clinical study to assess the safety and efficacy of MultiStem® therapy in subjects with Acute Respiratory Distress Syndrome (ARDS). Involvement: Clinical site selection and trial execution Health economics and reimbursement Finances: Innovate UK Collaborative R&D grant of £2.2m Outcome: Enables trial to be conducted in UK sites with Athersys. Opening of UK Subsidiary

Getting it commissioned

Issues with Delivery – the journey begins Understanding the clinical complexity Skills and training Logistics of ATMP’s – speed, access and storage Appropriate infrastructure funding in clinical delivery facilities – buy in from AHSC Managing expectations - patients already travelling abroad to access novel therapies eg autologous CAR-T in the USA or travelling to single EU centre for Strimvelis Defining scope and specifications for possible Centres of Excellence via the RM CRG?