6/19/2012

1. Ocular Programs
June 2012

2. This presentation is intended to present a summary of ACT’s (“ACT”, or “Advanced Cell
Technology Inc”, or “the Company”) salient business characteristics.
The information herein contains “forward‐looking statements” as defined under the federal
securities laws. Actual results could vary materially. Factors that could cause actual results
to vary materially are described in our filings with the Securities and Exchange Commission.
You should pay particular attention to the “risk factors” contained in documents we file from
time to time with the Securities and Exchange Commission. The risks identified therein, as
well as others not identified by the Company, could cause the Company’s actual results to
differ materially from those expressed in any forward‐looking statements. Ropes Gray
Cautionary Statement Concerning Forward‐Looking Statements
2

3. Multiple Pluripotent Cell Platforms
• Single Blastomere-derived Embryonic Stem Cells
• Generating hESC without Destruction of Embryo
• Utilizes a single cell biopsy
• Our hESC lines exhibit all the standard characteristics and the
ability to differentiate into the cells of all three germ layers
both in vitro and in vivo.
• Induced Pluripotency Stem Cells (iPS)
• Early Innovator in Pluripotency (before iPS was even a term!)
• Recipient of National Institutes of Health Director's Opportunity Award
• Seminal paper identifying replicative senescence issue for vector-derived iPS cells
• Leading publication on protein induced iPS lines - avoids genetic manipulation with nucleic acid vectors
• Controlling Filings (earliest priority date) to use of OCT4 for inducing pluripotency
3
Final Product Definition: hESC-derived
products will be manufactured using a cell
line made in 2005 from single cell isolated
without the destruction of any embryos

4. The RPE layer is critical to the function and health of photoreceptors and the
retina as a whole.
– RPE cells provide trophic support and detoxification activities to photoreceptor space.
» Recycle photopigments
» Deliver, metabolize and store vitamin A
» Phagocytize and clear cellular waste
» Maintain Bruch’s membrane
» Absorbs incident light, protects space from UV damage
– RPE loss leads to photoreceptor loss and eventually blindness, such as dry-AMD
– Loss of RPE layer and appears to lead to decline of Bruch’s membrane, leading
progression from dry-AMD to wet-AMD
• Discrete differentiated cell population as target
• Failure of target cells results in disease progression
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Retinal Pigment Epithelial Cells - Rationale
No other cell type can perform
this complete set of functions

5. 5
RPE Cell Therapy
Early Stage AMD
(10-15M)
Intermediate AMD
(5-8M)
Late Stage AMD
(1.75M)
U.S. Patient Population
ACT’s RPE Cell Therapy should effectively
address the full range of dry AMD patients.
• Halt the progression of disease and vision
loss in early stage patients
• Restore some visual acuity in later stage
patients
Dry AMD represents more than 90 percent of all
cases of AMD
North America and Europe alone have more than
30 Million dry AMD patients who should be
eligible for our RPE cell therapy
On the Rise: Population demographics
(“baby boomers”) combined with increased
longevity predicts an increase of 50 percent
or more in the incidence rate of AMD.

6. RPE Engraftment – Mouse Model
Human RPE cells engraft
and align with mouse RPE
cells in mouse eye
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Injected human RPE cells recapitulates
correct monolayer structure in eye
Human RPE cells fill in empty spaces
adjacent to mouse RPE cells
400x magnification
100x magnification

7. RPE Engraft and Function in Animal Studies
RPE treatment in RCS rat model of retinal dystrophy slowed the
progression of vision loss by promoting photoreceptor survival.
treated control
Photoreceptor
layer
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photoreceptor layer is
only 0 to 1 cell thick
without treatment
Treated animal – retain 70% of full visual acuity
Control Animal – blind at 6 months

8. • Established GMP process for differentiation and purification of RPE
– Virtually unlimited supply
– Pathogen-free GMP conditions
– Minimal batch-to-batch variation
– Characterized to optimize performance
– Virtually identical expression of RPE-specific genes to controls
GMP Manufacturing
Ideal Cell Therapy Product
• Centralized Manufacturing
• Small Doses
• Easily Frozen and Shipped
• Simple Handling by Doctor
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9. Characterizing Clinical RPE Lots
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Normal female (46 XX) karyotype
of the clinical RPE lot.
Up-regulation of RPE markers and
down-regulation of hESC markers

10. Characterizing Clinical RPE Lots
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Quantitative Potency Assay
Each lot is assessed by phagocytosis (critical
function in vivo) of fluorogenic bioparticles.
Flow cytometry histogram showing
phagocytosis of pHrodo bioparticles
4°C 37°C

11. Effects of Pigmentation
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Melanin content can be measured spectrophotometrically and used to determine the
optimal time to harvest and cryopreserve RPE.
y = 0.0141x + 0.0007
0.00
0.50
1.00
1.50
2.00
0 20 40 60 80 100120
Absorbanceat475nm
µg/mL Melanin

12. Phase I - Clinical Trial Design
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SMD and dry AMD Trials approved in U.S., SMD Trial approved in U.K.
• 12 Patients for each trial, ascending dosages of 50K, 100K, 150K and 200K cells.
• Patients are monitored - including high definition imaging of retina
High Definition Spectral Domain Optical Coherence Tomography (SD-OCT)
Retinal Autofluorescence
50K Cells 100K Cells 150K Cells 200K Cells
Patient 1 Patients 2/3
DSMB Review DSMB Review
RPE and photoreceptor activity
compared before and after surgery

13. Surgical Overview
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Procedure:
• 25 Gauge Pars Plana Vitrectomy
• Posterior Vitreous Separation
(PVD Induction)
• Subretinal hESC-derived RPE
cells injection
• Bleb Confirmation
• Air Fluid Exchange

14. Preliminary Results
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• Structural evidence confirmed cells had
attached and persisted
• No signs of hyperproliferation,
abnormal growth, or rejection
• Anatomical evidence of hESC-RPE
survival and engraftment.
• Clinically increased pigmentation
within the bed of the transplant
• Recorded functional visual
improvements in both patients

15. Images of hESC-RPE transplantation site in SMD Patient
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SD-OCT images
Demonstrate survival and engraftment of RPE
The injected RPE cells migrate to the desired anatomical location
3mo post-op

16. Phase II/III Design
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Design of future studies dependent upon information gathered
throughout PI/II study
• Efficacy
• Patient population less VA impact 20/200?
• Multiple Injections
• Further evaluation of I/E criteria
• Potentially less immunosuppression
• Other considerations of efficacy:
• New or more sensitive technologies
• Possible saline placebo injection (same eye)
Working with our
experts/investigators in
design of studies

17. Phase II/III Projected Timeline
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• Completion of Phase I/II study 2013-2014
• Design of Phase II and III studies is an ongoing
process, but will become more concrete during
2013
• Phase III study commencement 2014-2015

18. RPE Cells – Additional Indications
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• Myopic Macular Dystrophy (MMD)
• Retinopathy of Prematurity
• Angioid Streaks
• Retinitis Pigmentosa
• Bests Disease (vitelliform macular dystrophy)
• Multifocal Choroidopathy Syndromes
Combination Products
• Combined with other cell types (photoreceptor progenitors)
• Combined with anti-angiogenic agents, neuroprotective agents, etc.

19. Therapeutic Pipeline -
Ocular Programs

20. 20
Retinal Pigment Epithelial Cells
 Macular Degeneration - dry AMD, Stargardt’s Disease, MMD
 Retinitis Pigmentosa
 Photoreceptor protection
Hemangioblast cells
 Ischemic retinopathy
– diabetic retinopathy, vascular occlusions
Retinal Neural Progenitor cells
Isolated Protective Factors
 Photoreceptor Loss, Modulation of Müller Cells
 Protection of Retinal Ganglion cells (Glaucoma)
Corneal Endothelium, Corneal Epithelium,
Descemet’s Membrane
 Corneal Disease
Mesenchymal Stromal Cells
 Glaucoma, Uveitis
 Retinitis Pigmentosa
 Management of Ocular Surfaces
light
retina
RPElayer
Photoreceptors

21. Ocular Program – Corneal Endothelium
• More than 10 million people with corneal blindness
• The cornea is the most transplanted organ (1/3 of all
transplants performed due to endothelial failure)
• Solutions include the transplantation of whole cornea
“Penetrating Keratoplasty” (PKP)
• More popular: Transplantation of just corneal
endothelium & Descemet’s membrane (DSEK/DSAEK).
hESC-derived corneal
endothelium resembles
normal human corneal
endothelium
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22. Ocular Program – Hemangioblasts
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Hemangioblasts induce reparative
intraretinal angiogenesis is various
animal models of ischemic retinopathies
• Revascularization is observed in animals
injected either intravitreally or intravenously with
hESC-derived hemangioblasts
• ischemia-reperfusion injury
• diabetic retinopathy
• GFP-labeling reveals incorporation of injected
cells into the vasculature of the eye during
angiogenesis
• Hemangioblasts prevented BRB breakdown in
diabetic rats.
Repair of ischemic retinal vasculature in a mouse
after injection of hESC-derived hemangioblasts

23. Ocular Program – Hemangioblasts
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Oxygen-induced Retinopathy Model
OIR+HBOIR+dPBS
hESC-derived
Hemangioblasts Rebuild
Functional Vasculature on
Retina Obliteration Region
and Suppress Pre-retinal
Neovascular Tufts

24. • Generated various retinal neural progenitor cell types – or RNP cells
• From both embryonic and iPS cell sources.
• Discovered a new photoreceptor progenitor cell type.
• Tested in mouse model for retinal degeneration - ELOVL4-TG2 mice
• Observed both structural and physiological consequences
After 2 months
• ERG - increases in both the a-wave and b-wave
• OCT - increases in central retinal thickness
Ocular Program – Retinal Neural Progenitors
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hESC-derived RNP cells reversed the progression of photoreceptor
degeneration– and appeared to promote regeneration
• Defined culture conditions
• High yield from hESC and iPS
• Homogeneous and highly pure
preparations

25. ACT Management Team
Highly Experienced and Tightly Integrated Management Team
Gary Rabin – Chairman & CEO
Dr. Robert Lanza, M.D. – Chief Scientific Officer
Edmund Mickunas – Vice President of Regulatory Affairs
Kathy Singh - Controller
Rita Parker – Director of Operations
Dr. Irina Klimanskaya, Ph.D. – Director of Stem Cell Biology
Dr. Shi-Jiang (John) Lu, Ph.D. – Senior Director of Research
Dr. Roger Gay, Ph.D. - Senior Director of Manufacturing
Dr. Matthew Vincent, Ph.D. – Director of Business Development
Bill Douglass – Director of Corporate Communications & Social Media
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26. Thank you
For more information, visit www.advancedcell.com