Ocular ProgramsJune 2012

This presentation is intended to present a summary of ACT’s (“ACT”, or “Advanced CellTechnology Inc”, or “the Company”) salient business characteristics.

The information herein contains “forward‐looking statements” as defined under the federalsecurities laws. Actual results could vary materially. Factors that could cause actual resultsto 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 fromtime to time with the Securities and Exchange Commission. The risks identified therein, aswell as others not identified by the Company, could cause the Company’s actual results todiffer materially from those expressed in any forward‐looking statements. Ropes Gray

Cautionary Statement Concerning Forward‐Looking Statements

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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

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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

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

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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.

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

RPE Engraft and Function in Animal StudiesRPE treatment in RCS rat model of retinal dystrophy slowed the progression of vision loss by promoting photoreceptor survival.

treated control

Photoreceptorlayer

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photoreceptor layer isonly 0 to 1 cell thickwithout treatment

Treated animal – retain 70% of full visual acuityControl Animal – blind at 6 months

• 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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Characterizing Clinical RPE Lots

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Normal female (46 XX) karyotypeof the clinical RPE lot.

Up-regulation of RPE markers and down-regulation of hESC markers

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

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

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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

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

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

Images of hESC-RPE transplantation site in SMD Patient

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SD-OCT imagesDemonstrate survival and engraftment of RPEThe injected RPE cells migrate to the desired anatomical location

3mo post-op

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

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

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.

Therapeutic Pipeline -

Ocular Programs

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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 cellsIsolated 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

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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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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

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

• 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

ACT Management TeamHighly Experienced and Tightly Integrated Management Team

Gary Rabin – Chairman & CEODr. Robert Lanza, M.D. – Chief Scientific OfficerEdmund Mickunas – Vice President of Regulatory AffairsKathy Singh - ControllerRita Parker – Director of OperationsDr. Irina Klimanskaya, Ph.D. – Director of Stem Cell BiologyDr. Shi-Jiang (John) Lu, Ph.D. – Senior Director of ResearchDr. Roger Gay, Ph.D. - Senior Director of ManufacturingDr. Matthew Vincent, Ph.D. – Director of Business DevelopmentBill Douglass – Director of Corporate Communications & Social Media

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Thank youFor more information, visit  www.advancedcell.com