2. The Problem
 “Dry” Age-Related Macular Degeneration
 Slowly progressing thinning of the macula
 Widespread oxidative damage known as Geographic Atrophy
 Responsible for central vision loss
 No approved treatments beyond supplements
 Impedes critical activities such as reading, driving and
distinguishing faces
 Incident rates increase with age
 Number #1 cause of visual loss in developed countries in those over
50 years of age

3. The Proposed Solution
Encapsulated allogenic neural stem cells
Injected subretinally
Secrete paracrine factors known to
stimulate neuroprotection of existing cells
Removable post-efficacy or in safety
concern
Preserve visual acuity safely and
effectively

4. Encapsulated
Allogenic
Stem Cells
Fujifilm’s
J-TEC
Japanese
Dry AMD
Market
Differentiation
Specifications
Regulatory
Viability
Development
Unmet Need
Abenomics
Demographics
Race to Entry
Access &
Affordability
IP
Experience
Buyer, Deciders
& End Users
Capital
Commercialization
Capabilities
Dry AMD focus
Regenerative
medicine

5. THE TECHNOLOGY

6. The Specifications: The Cells
 The cells: HuCNS-SC® human neural stem cells
 “Uses monoclonal antibodies against specific
cell surface markers to prospectively isolate
the population of neural stem cells from human
brain tissue, and then purify and expand these
cells into cryopreserved cell banks.”
-Stem Cells Inc.
 Unmodified; no reprogramming
 Highly purified
 Non-controversial origin
 Primary efficacy and safety already establishing
in Phase I/II studies
 Cell Bank and full scale cGMP manufacturing
already achieved

7. The Capsules
 Sodium Cellulose Sulfate consisting of polymers
of SCS and polydiallyldimethyl ammonium
chloride
 Good biocompatibility for cells
 3 x 0.75 mm in size and contain thousands of
cells each
 Pores are big enough to allow nutrients to diffuse in and waste
products out
 Permissive for the release of the therapeutic paracrine factors
 Small enough to deny access to immune cells such as T-cells,
macrophages, and neutrophils

8. Mechanism of Action
• Degeneration of neural cells in the retina are hallmarks
to AMD
• Allogeneic RPE cells do not attach to Bruch’s membrane
efficiently
• Retinal Stem Cells can be found in the pigmented ciliary
margin
• Differentiate into retinal-specific cell types,
including rod photoreceptors, bipolar neurons, and
Müller glia
• To rescue retinal neurons from further degeneration this
therapy will rely on the growths factors involved in the
development and maintenance of retinal neurons
• Transforming growth factor (TGF-beta 3)
• Fibroblast growth factor (FGF)
• Epidermal growth factor (EGF)
• Hepatocyte growth factor/scatter factor (HGF/SF)

9. Why Encapsulate?
 Allogenic “one size fits all” convenience
 No need for immunosuppressive
therapy
 Can be frozen
 Validated shipping method; cells
have lasted up to 5 years
 Preferred by regulators
 Robust; can be delivered through
needles
 Capsules have been tested in clinical
trials and were efficacious and safe
in the body for up to two years
 Can be localized to site of
treatment
 Higher accuracy
 Longer distribution
 Lower doses
 Lack of fibrous overgrowth

10. Alternatives Considered
Approach Reason for Rejection
Neuroreplacement
Huge amounts of competitors are using this approach; concerns about
immune rejection; high cost, low convenience of autologous
treatments; cell migration and tumorigenic capabilities; requires
larger amount of starting materials. Also muddying a replacement
approach is the precision of donor cell integration, the vascular
complexity, and the complex mechanisms of secondary synaptic
rewiring
ESC Controversial origins
iPSC
New, early in human use; delayed market entry; unknown regulatory
obstacles; QC Concerns and technical challenges including
pseudogenes, regions rich in AT, and genes too long to sequence due to
software considerations, and potential server of other technical fails
Alginate capsules Cannot be frozen; limits shipping and distribution options
Combination w non-stem cell
progenitor cells
Requires immunosuppressive therapy or autologous approach
• Decorating the capsules with additional growth factors
• Genetically modifying cells to enhance growth factor expression
• Using a different location for delivery: intravitreal, intraretinal, or on the ciliary margin where RSCs are located
• Tandem approach with non-stem cell progenitor cells could boost the paracrine factor efficacy

11. Implementation: Pros and Cons
 Pros:
 Ease of manufacture and distribute
 Capsule materials are easily sourced and cryopreserved
 Large scale cGMP manufacturing has been achieved for both
components achieved
 AustriaNova offers Proof of Concept services
 Less uncertainty results in faster time to market and lower
costs
 Cons:
 Estimated have regenerative treatments costing as much as
$512K per treatment
 Licensing must be favorably resolved

12. Current Uses
 HuCNS-SC® are used investigationally for spinal
cord injury, Pelizaeus-Merzbacher Disease, and
Neuronal Ceroid Lipofuscinosis
 Stem cells + microenvironments such as
encapsulation or a hydrogel matrix are being
researched for cardiovascular disease, Huntington’s
Disease, ALS, and Parkinson’s
 Cell encapsulation already used for indications
including diabetes, cancer, cardiovascular,
monoclonal antibody therapies, and liver failure
 Future use: other retinal disorders like Retinitis
Pigmentosa or Stargardts or possibly even
Alzheimers

13. The Market

14. Market Considerations: Pros and Cons
 Pros
 Unmet Need
 National economic policy supporting regenerative innovation
and adoption
 Japan’s defined and expedited regenerative regulatory
channels
 World’s oldest population
 Cons:
 Densely packed research space: race to entry
 Other investigational treatments in Phase II
 Expensive to produce or consume
 Signs of a shift in economic policy
 Aging population=dwindling tax base that pays for healthcare

15. Japan’s Expedited Regulatory Pathway

16. The Competition
Treatment Competitor Method/Strategy Delivery
Route/frequency if
Indicated
Stage of
Development
Lampalizumab Roche Biologic: Anti-factor D
monoclonal antibody
Intravitreal Injection Phase III
GSK933776 GSK Biologic: Humanized
mouse IgG1 monoclonal
antibody target FC
receptor binding
IV Phase II
MacuCLEAR MC-1101
1.0%
MacuClear Inc. Drug designed to reduce
choroidal blood flow
Topical: Drops/BID Phase II/III
Bone Marrow CD34
Stem cells
UC-Davis Regenerative:
neuroreplacement or
neuroprotection
Single Intravitreal
injection, 200,000 cells
Phase I
hESC derived RPE Cells Astrellas Pharma Regenerative:
neuroreplacement or
neuroprotection
Single Sub-retinal
injection
Phase I/II
Autologous Bone
Marrow Stem Cells
Retinal Associates of
South Florida/ MD Stem
Cells
Regenerative:
neuroreplacement or
neuroprotection
Injections of BMSC
retrobulbar, subtenon
and IV
Unspecified
HuCNS-SC Stem Cells Inc Regenerative:
neuroreplacement
Single Sub Retinal
injection. 1 million cells
Phase I/II
Brimonidine Allergan Drug for neuroprotection
through alpha-
adrenergic agonist
Eight Intravitreal
Implants
Phase II
LEAD Laser Center for Eye Research
Australia
Procedure applied to
early stage druse
2RT Nanaosecond Laser Unsepcified
Autologous iPSC Cellular Dynamics Inc.:
a Fujifilm Group
Company
Regenerative:
neuroreplacement or
neuroprotection
Implanted on scaffolding Pre-clinical

17. THE COMPANY

18. Strategic Analysis: Pros and Cons
 Pros:
 Fujifilm is dedicate to regenerative medicine and AMD
 Series of acquisitions: Diosynth Biotech, Kalon, J-TEC, and CDI
 Has capital and capabilities in development, clinical, regulatory,
manufacturing, quality, HR, finance, legal, project management and
marketing
 Japanese Tissue Engineering Company has 3 approved regenerative
treatments using somatic stem cells
 Cons:
 J-TEC strategy is tissue engineering
 Have process for autologous stem cells, not allogenic
 No stake in IP; licensing needed
 No experience with encapsulation
 Tech could get lost within expansive portfolio

19. Summary
 Technology has merit
 Existing IP
 Established manufacturing
 But there is a long way to go
 Early stage
 Research space is crowded
 What if other approaches are faster, safer or more effective?
 Japanese market has strong indicators but
 Political and regulatory advantages are temporary and reproducible by competitors
 Relies on government’s long-term ability to pay
 Fujifilm and J-TEC offers capital and experience
 Valuable but not unique
 Does not match J-TEC’s corporate strategy
 May get lost in portfolio

20. Final Recommendation
 Do not invest in this technology proposal
 Consider alternatives to solve the dry AMD problem
 Start with Japan to get earliest market entry but, once
proof of concept is established and regulatory processes
more clearly defined, pursue multinational approval and
sales
 Look at companies with later stage solutions
 Consider acquiring entire company to maintain
experience and internal support for the tech
 Contemplate buying a competitor to narrow the field
Thank you very much for your time and attention!