1. 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

2. UK Industry growth 2012 to 2015 $500m+ 42 +90% +1,000 +50% +70%
Investment 2015
¹Investment attracted by UK companies in 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

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

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

5. The typical pathway

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

7. 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 -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

8. 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

9. 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

10. Getting it commissioned

11. 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?