1. Cell Therapy in Big Pharma:
The Pfizer Neusentis Approach
Natalie Mount PhD
Executive Director
Neusentis Regenerative Medicine
Stem Cells USA and Regenerative Medicine Congress
Sept 2011
Neusentis is a wholly owned subsidiary of Pfizer

2. 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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3. 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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4. 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
symptomsRelieve
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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5. 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

6. Our Portfolio: hEs Differentiated Cells –
University College, London Collaboration
Pfizer Confidential
 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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7. 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

8. 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 preparation
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9. Clinical development program goals
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Phase 1
Phase 2a
Phase 2b
Phase 3
(Phase 3b/4)
Safety in relevant population
Explore dose/dosing regimen
Pharmacodynamics / mechanism
Robust evidence of efficacy (randomised, double
blind, placebo controlled)
Explore trial population
Build safety
Finalise dose / dosing regimen
Confirm trial population and background therapy
Select 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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10. Our Portfolio: Allogeneic Adult Stem Cell
Therapy for IBD - Athersys Collaboration
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Pfizer Confidential
 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

11. 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 tolerability
Efficacy 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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12. Overview of MultiStem® Production Process
Lot Release & Product
Characterization Testing
Sterility
Potency
Identity and Viability
Stable Cytogenetics
Absence of ectopic tissue potential in vivo
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13. 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 cell
B cell (immature, naïve, isotype
switched memory and marginal
zone)
Analysis will be based on
changes
observed 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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14. 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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15. 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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