Roth Capital 24th Annual Growth Stock Conference, Los Angeles

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Leading Regenerative Medicine Investor Presentation March 2012

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4/13/2012

Transcript of Roth Capital 24th Annual Growth Stock Conference, Los Angeles

Page 1: Roth Capital 24th Annual Growth Stock Conference, Los Angeles

Leading Regenerative Medicine

Investor Presentation – March 2012

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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

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ACT 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 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

RP

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yer

Pho

tore

cept

ors

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The RPE layer is critical to the function and health of photoreceptors and the retina as a whole.

– RPE cells secrete trophic factors and impact on the chemical environment of the subretinal space.

» recycle photopigments

» deliver, metabolize and store vitamin A

» transport iron and small molecules between retina and choroid

» maintain Bruch’s membrane

– RPE loss may lead to photoreceptor loss and eventually blindness, such as dry-AMD

– Loss of RPE layer and Bruch’s membrane is substantial feature underlying development of dry-AMD, and may be involved in progression from dry-AMD to wet-AMD

• Discrete differentiated cell population as target

• Failure of target cells results in disease progression 5

Retinal Pigment Epithelial Cells - Rationale

RPE cell as Target

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• Pigmented RPE cells are easy to identify (no need

for further staining) – impacts manufacturing

• Small dosage vs. other therapies

• The eye is generally immune-privileged site, thus

minimal immunosuppression required, which may be

topical.

• Ease of administration – Doesn’t require separate approval by the FDA (universal applicator)

– Procedure is already used by eye surgeons; no new skill set required for doctors

RPE cell therapy may impact over

200 retinal diseases 6

Retinal Pigment Epithelial Cells - Rationale

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• Established GMP-compliant process for the Reproducible Differentiation and Purification of RPE cells. – Virtually unlimited supply of cells

– Can be derived under GMP conditions pathogen-free

– Can be produced with minimal batch-to-batch variation

– Can be thoroughly characterized to ensure optimal performance

– Molecular characterization studies reveal similar expression of RPE-specific genes to controls and demonstrates the full transition from the hESC state.

GMP Manufacturing

Ideal Cell Therapy Product • Centralized Manufacturing

• Small Doses that can be Frozen and Shipped

• Relative Ease-of-Handling by Doctor

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RPE Engraftment – Mouse Model

For each set: Panel (C) is a bright field image and

Panel (D) shows immunofluorescence with anti-

human bestrophin (green) and anti-human

mitochondria (red) merged and overlayed on the

bright field image. Magnification 400x

Human RPE cells engraft

and align with mouse RPE

cells in mouse eye

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RPE Engraft and Function in Animal Studies

RPE treatment in animal model of retinal dystrophy has slowed the natural progression of the disease by promoting photoreceptor survival.

RPE cells rescued photoreceptors and

slowed decline in visual acuity

treated control

Photoreceptor

layer

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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.

– For each cohort, 1st patient treatment followed by 6 week DMSB review before remainder of cohort.

• 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

Permit comparison of RPE and

photoreceptor activity before

and after treatment

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RPE Clinical Program – to date

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• Dry AMD • IND approved in December 2010

• European CTA in preparation

• Stargardt’s (SMD) Disease • IND approved in November 2010

• European CTA Approved

• Orphan Drug Designation granted in U.S. and Europe

ClinicalTrials.gov US: NCT01345006, NCT01344993 UK: NCTO1469832

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RPE Clinical Program – to date

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Attracting Top Eye Surgeons and Retinal

Clinics to participate in Clinical Trials,

DSMB and Scientific Advisory Board

Dr. James Bainbridge, Moorfields Eye Hospital

• US Clinical Trial Sites • Jules Stein Eye (UCLA)

• Wills Eye Institute

• Status • 2nd and 3rd SMD patients treated (Jan/Feb 2012)

• Completes Cohort 1 (US)

• Enrolling additional dry AMD patients

• Additional Major Clinical Sites to announce

• European Clinical Trial Sites • Moorfields Eye Hospital

• Aberdeen Royal Infirmary

• Status • 1st SMD (Europe) patient treated (20 January 2012)

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Surgical Overview • Prospective clinical studies to determine the safety and tolerability of

sub-retinal transplantation of hESC-derived RPE cells.

• Subretinal injection of 50,000 hESC-derived RPE cells in a volume of

150µl was delivered into a pre-selected area of the pericentral macula

• Vitrectomy including surgical induction of posterior vitreous separation

from the optic nerve was carried out

• 25 Gauge Pars Plana Vitrectomy

• Posterior Vitreous Separation (PVD Induction)

• Subretinal hESC-derived RPE cells injection

• Bleb Confirmation

• Air Fluid Exchange

Drs. Steven Schwartz and Robert Lanza

Straight forward surgical approach Can be performed on outpatient basis

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Surgical Overview

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Autofluorescence

images of retinas.

The dark spots in the

side panels show a

large area of atrophy in

the macular region.

First SMD Patient

First dry AMD Patient

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Surgical Overview

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Surgical Overview

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Remove gel from

inner surface of retina

Injection with bleb

formation

Air Fluid Exchange

Injection bleb formed at interface of

atrophic retina and normal retina

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Preliminary Results

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• Dry AMD • The dry AMD patient is a 77 year old female with baseline

BCVA of 20/500, that corresponded to 21 letters in the ETDRS chart.

• Stargardt’s (SMD) Disease • The SMD patient is a 51 year old female with baseline best corrected visual acuity

of hand motion that corresponded to 0 letters in the ETDRS chart.

July 12, 2011: First Patients in each trial

were treated by Dr. Steven Schwartz, M.D

at Jules Stein Eye Institute (UCLA)

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Preliminary Results

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• After surgery, structural evidence

confirmed cells had attached and

continued to persist during study.

• No signs of hyperproliferation,

abnormal growth, or immune mediated

transplant rejection in either patient.

• Anatomical evidence of hESC-RPE

survival and engraftment.

• Clinically increased pigmentation at the level of the RPE within the bed

of the transplant beginning at postoperative week 1.

23 January 2012

Published results for first SMD and

Dry AMD Patients – 4 month time point

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Preliminary Results

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Recorded functional visual improvements in

both patients.

• SMD Patient: Best corrected visual acuity

improved from hand motions to 20/800 and

improved from 0 to 5 letters on the ETDRS

visual acuity chart in the study eye.

• Dry AMD Patient: Vision improved in the

patient with dry age-related macular

degeneration (21 ETDRS letters to 28).

Six Month Follow-up: Visual acuity gains remain stable for both patients; SMD Patient has slight improvement.

Similar trends observed for latest 3 SMD patients

SMD Patient

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Images of hESC-RPE transplantation site in SMD Patient

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pre-transplant 1wk post-op 6wk post-op

Color fundus photographs

We detected clinically increased pigmentation at the level of the RPE within the

bed of the transplant beginning at postoperative week 1 to month 3

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Images of hESC-RPE transplantation site in SMD Patient

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SD-OCT image collected at month 3 show survival and engraftment of hESC-RPE.

Localization of the transplanted cells to the desired anatomical location.

3mo post-op

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Media Coverage

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First Hints That Stem Cells Can

Help Patients Get Better

Headline: “Stem Cell Treatment for Eye Diseases Shows Promise”

Headline: “Some Promising Findings on Embryonic Stem Cells”

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Intellectual Property – RPE Program

Dominant Patent Position for Treating Retinal Degeneration • US Patent 7,794,704 broadly cover methods for treating retinal degeneration using human RPE cells differentiated from

human embryonic stem cells (hESCs).

Broad Coverage for Manufacturing RPE Cells from hESC • U.S. Patents 7,736,896 and 7,795,025 are broadly directed to the production of retinal pigment epithelial (RPE) cells from

human embryonic stem cells.

Coverage for RPE Cells derived from other pluripotent stem cells (including iPS cells) • Earliest priority date relates back to 2004 filings

• Methods of manufacturing, use of RPE cells, and pharmaceutical formulations – e.g., source cell defined as pluripotent stem cell that expresses Oct-4, alkaline phosphatase, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81.

Vigilant Filing on Improvements • Extends patent life cycle, with significance to commercialization

• Include composition-of-matter claims (cell preparations, pharmaceutical preparations, etc.)

• Examples: degree of pigmentation, cell density of preparation, phagocytic activity • Distinguished from adult RPE cell preparations - telomere length, A2E and lipofuscin content of cells, lack of accumulated UV damage

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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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The Hemangioblast cell is a multipotent cell, and a common precursor to hematopoietic and endothelial cells.

Hemangioblast cells can be used to

produce all cell types in the circulatory

and vascular systems

• Hemangioblast cells can self-renew.

• Hemangioblast cells can be used to achieve

vascular repair.

• Hemangioblast activity could potentially be

harnessed to treat diseases such as myocardial

infarction, stroke, cancer, vascular injury and

blindness.

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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

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• 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

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Ocular Program – Mesenchymal Stromal Cells

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Proprietary Large Scale

Manufacturing Process for

Generating “young” MSCs

from hESC and iPS lines

• hESC-MSCs and iPS-MSCs can be expanded to large

numbers in vitro • Avoid premature senescence problem of “old” MSC’s

• Superior quality controls for a renewable cell source

• “Off-The-Shelf” therapy, available for immediate use

• Projected Higher Immunosuppressive Potency relative to adult

MSC

• MSCs can migrate to injury sites in eye – exert

immunosuppressive effects, and facilitate repair of

damaged tissues

Ocular Products in Development ▫ Treating inflammatory diseases of the eye

▫ Providing photoreceptor/neuron-protective activity

▫ Promoting tolerance to ocular grafts and devices

▫ Delivering therapeutic proteins to the eye.

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Ocular Program – Mesenchymal Stem Cells

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33,000 units MSCs from hESC-MSCs

1 unit MSCs

from adult BM

Compared to Adult MSC

• Less labor-intensive

• Single Bank Regulatory Process No need to derive new banks

Quality controls are easier to manage

• Larger yield of MSCs

Compared to hESC-direct

• Less labor-intensive

• Larger yield of MSCs

• Faster Acquisition of Markers

hESC Direct HB Method

Start 350,000 ESC 200,000 EB’s

Collect 48 days 44 days

Yield 4 Million 85 Million

Manufacturing Considerations Favor

hESC/Hemangioblast-derived MSC’s

over Adult MSC and hESC-direct MSC

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Platform Technology for Generating

Robust Human Embryonic Stem Cells

Without the Need to Destroy Embryos

Single Blastomere Technology

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Generating hESC without Destruction of Embryo • Enables Derivation of new hESC Lines via non-destructive single cell

biopsy method

• Utilizes single cell biopsy similar to pre-implantation genetic diagnostics

(PGD) Does not change the fate of the embryo from which the

biopsy was taken

• Blastomere-derived hESC lines exhibited all the standard characteristics:

undifferentiated proliferation, genomic stability, expression of pluripotency

markers and the ability to differentiate into the cells of all three germ layers both

in vitro and in vivo.

• Roslin Cells and ACT plan to generate GMP-compliant bank of human ES Cells

for research and commercial uses.

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Worldwide Patent Filings

Issued Broad Claims to Single Blastomere Methodology - U.S. Patent 7,893,315

CONFIDENTIAL

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iPS Platform

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• Recipient of National Institutes of Health Director's Opportunity Award

• Seminal paper identifying replicative senescence issue for vector-derived iPS cells • Feng et al. (2010) Stem Cells. 28(4):704-12.

• Leading publication on protein induced iPS lines • Generated stable iPS cells from human fibroblasts by directly delivering reprogramming proteins

associated with cell penetrating agents.

• Avoids replicative senescence problem in vector-induced iPS.

• Kim et al. (2009) Cell Stem Cell. 4(6):472-476.

• Pending patent filings directed to protein induced iPS.

Early Innovator in Pluripotency (before iPS was even a term!)

• Controlling Filings (earliest priority date) to use of OCT4 for inducing pluripotency Beats Yamanaka priority by several years

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Financial Update – Strong Balance Sheet

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Most Stable Financial Situation In Company History

• The Company ended 2011 with $13.1 million cash on hand

• $15 million more equity available

• Virtually debt-free

• Able to self-fund both U.S. clinical trials and EU clinical trial

• Significantly deepened management team (and on-going)

• Put in place first organizational reporting lines in ACT history

• Robert Langer, Zohar Loshitzer and Greg Perry join ACT board, bringing

remarkable scientific, entrepreneurial and partnering skills

• One additional Board member to announce

• Unqualified audit opinion

Continuing clinical trials with a strong balance sheet

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ACT Management Team

World Class Scientific Team

Seasoned Management Team

Dr. Robert Lanza, M.D. – Chief Scientific Officer

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

Gary Rabin – Chairman and CEO

Edmund Mickunas – Vice President of Regulatory Affairs

Kathy Singh - Controller

Rita Parker – Director of Operations

Bill Douglass – Director of Corporate Communications & Social Media

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Thank you For more information, visit www.advancedcell.com