Cell Therapy in Big Pharma:The Pfizer Neusentis Approach

Natalie Mount PhDExecutive Director

Neusentis Regenerative Medicine

Stem Cells USA and Regenerative Medicine CongressSept 2011

Neusentis is a wholly owned subsidiary of Pfizer

Presentation overview

• Introduction to Neusentis Regenerative Medicine:• Strategy and vision

• Selected cell therapy case studies from our portfolio

• Challenges and opportunities for cell based therapy in big pharma:

• Development• Commercialisation

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Our Vision & Strategic Themes in Regenerative Medicine

Build an industry leading group of scientists and partners to discover, develop and launch innovative cell based therapies to patients

• Build knowledge and expertise (clinical, regulatory, safety, logistical) in cell therapy to enable successful development of products

• Evaluate allogeneic, autologous and hES cell based approaches• Identify soluble factors that modify cell fate

• Build knowledge on business models for a cell based therapy and how to enable a future successful commercial launch

• Partner with the Pfizer Business Units to understand key issues in commercialization of a cell based therapy

• Partner externally as much as possible to access the best science and accelerate development of the best approaches

Science

Commercial

Partnering

Vision

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The Potential For Cell Based Products Is From Disease Modification To Cure

Source: The Frankel Group LLC

Biologics Tissue Engineering

Cell-Based Products

OTC Pharmaceuticals

Correct defect,

regenerate tissue

Relieve first-order

symptoms Relieve second-order

symptoms

Increasing Value of Treatment to

Patient

OTC=Over The Counter

Disease Modification

Increasing Revenue /

Patient

Replace defective

organ/tissue

Small Molecules

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Cell Therapy

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What different approaches are we taking to regenerative medicine?

• Allogeneic adult stem cell therapy• e.g. Athersys MultiStem collaboration

• Therapeutic administration of differentiated cells derived from embryonic (or iPS) cells

• e.g UCL RPE collaboration

• Small molecule & biologic modifiers of endogenous stem cells

• Autologous stem cell therapy

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‘The development of products (small molecules, biologics, cells) that restore function in damaged or aging tissues and organs’

Underpinned by knowledge of : - stem cell science- developmental pathways

Our Portfolio: hEs Differentiated Cells –University College, London Collaboration

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A stem cell derived therapy to replace retinal pigment epithelial (RPE) cells and restore retinal function for patients with macular degeneration

RPE project collaboration drivers: Highly respected academic and medical partners (University College,

London, Institute of Ophthalmology and Moorfields Eye Hospital) Strong rationale Non-integrating, well-characterised cells Low cell number required Synergy with Pfizer’s Ophthalmology disease area

3 clinical populations may benefit from RPE replacement: RPE tear: no current treatment, results in blindness in affected eye Wet Age-related macular degeneration (AMD): choroid pushes through

weakened RPE junctions leading to bleed into back of eye – currently treatment is anti-VEGF

Dry AMD: retina detaches from its support due to build-up of retinal debris, slow progression; no major treatment available

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Our Portfolio: hEs Differentiated Cells -UCL/Pfizer Collaboration

Differentiate human embryonic stem cells (hESC) into RPE

Seed RPE on immobile support

Place matrix + cells behind retina under fovea

1.5 mm

Fovea

Macula

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En face view of polyester membrane seeded with RPE cells

Challenges for development of cell based therapies

• Cell biology – cell selection, characterization and control

• Toxicology program – design and interpretation, cell tracking

• Mechanism of action

• Clinical trial design – safety; dose and dosing regimen; determination of efficacy

• CMC (cells, process, devices) and manufacturing at scale

• Trial supply logistics – centralised vs point of care preparationPfizer Confidential

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Clinical development program goals

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Phase 1

Phase 2a

Phase 2b

Phase 3

(Phase 3b/4)

Safety in relevant populationExplore dose/dosing regimenPharmacodynamics / mechanism

Robust evidence of efficacy (randomised, double blind, placebo controlled)Explore trial populationBuild safety

Finalise dose / dosing regimenConfirm trial population and background therapySelect endpoints (Regulatory authority and payor)Safety

Confirm efficacy and safety to support registration, label claims and reimbursement

Initial product manufacturing process

Scaled near-final manufacturing process

Finalised manufacturing process

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Our Portfolio: Allogeneic Adult Stem Cell Therapy for IBD - Athersys Collaboration

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MultiStem® Adult multipotent progenitor stem cell therapy for Inflammatory Bowel Disease

Collaboration drivers: Synergy of vision for a product in this area between management teams MultiStem® previous clinical experience Strong rationale Well-characterised and highly expandable cells Pfizer’s experience in running trials and developing therapies in IBD

Development of MultiStem for IBD has progressed very quickly since the collaboration was signed late December 2009: IND approval November 2010 Clinical trial to demonstrate safety and efficacy in moderate-severe

ulcerative colitis started Feb 2011

FDA has approved ulcerative colitis clinical trial

Low dose regimen

Cohort 1 (safety)High dose regimen

Cohort 2 (safety)High dose regimen

Cohort 3 (efficacy)

Population: Patients with moderate-severe ulcerative colitis; n=126

Main Objectives:Safety and tolerabilityEfficacy as measured by effect on disease (rectal bleeding and endoscopic healing)

Design: Double blind, randomised, placebo controlled, parallel group, efficacy assessments at 4 & 8 weeks

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Overview of MultiStem® Production Process

Lot Release & Product Characterization Testing

SterilityPotency

Identity and ViabilityStable Cytogenetics

Absence of ectopic tissue potential in vivo

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Pharmacodynamic Markers

Cell populations(by FACS)

Serum proteins(by Multiplex ELISA)

[RNA changes in blood and biopsies]

Examine ‘change from baseline’ across the dosing period

Link changes in cell population with changes in protein (and potentially RNA) expression

Assay panels to examine numbers of and activity of:

T-cell (naive & memory subsets, Tregs)NK cellB cell (immature, naïve, isotypeswitched memory and marginal zone)

Analysis will be based on changesobserved in FACS, ELISA and/or pre-clinical animal model

Measurement of ~90 proteins found in serum - includes cytokines, chemokines

and other bioactive proteins

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Challenges for commercialisation of cell based therapies

• Manufacturing requires the most differentiated capabilities and contributes disproportionately to the cost of treatment

• Building the business case:• Efficacy, safety and differentiation in chosen disease indication• Supply model• IP• Pricing and reimbursement

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Summary

• Developing cell based therapies brings unique Development and Commercialisation challenges

• Excellence in clinical program design can mitigate risk through a framework whereby the goals of each phase are clearly established and integrated with manufacturing investments to deliver a de-risked product

• In Neusentis Regenerative Medicine, we have made investments across technology platforms to create a diversified portfolio, to systematically address development and commercialization challenges, and provide flexibility to move quickly as the science breaks

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