Catapult is a Technology Strategy Board programme

Clinical development of cell based therapies in the UK

Natalie Mount PhDChief Clinical OfficerCell Therapy CatapultNov 2013natalie.mount@ct.catapult.org.uk

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

5

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

9

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

11

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

16

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?

17

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