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Leading Regenerative MedicineSeptember 2011
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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At the Forefront of Regenerative Medicine
• Patented Technology for Producing hESCs without Harm to Embryo• Working with Roslin Cells to create GMP-compliant hESC bank
• 2 Human Clinical Trials utilizing hESC-derived Retinal Pigment Epithelial Cells• First Patients Treated on July 12, 2011
• Stargardt’s Disease, aka Stargardt’s Macular Dystrophy (SMD)
• Dry AMD – (Dry Age-Related Macular Degeneration)
• Expecting Preliminary Safety and Engraftment Data by Year-End
• Commencing European Trials – estimated first half 2012
• Front-of-the-eye programs: Generating hESC-derived corneal tissues
• Finalizing preclinical work for blood product IND from hemangioblast program
• Generation of off-the-shelf hESC-derived mesenchymal stromal cells products
• Myoblast program for heart failure approved for Phase II
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ACT Ocular Programs
• 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 malfunction may lead to photoreceptor loss and eventually blindness
Discrete differentiated cell population
Failure of RPE results in disease progression5
Retinal Pigment Epithelial Cells - Rationale
• Pigmented RPE cells are easy to identify (no need
for further staining)
• 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 diseases6
Retinal Pigment Epithelial Cells - Rationale
• 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
• 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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• Stargardt’s (SMD) Disease • IND approved in November 2010
• European CTA filed
• Orphan Drug Designation granted in U.S. and Europe
• The SMD patient is a 46 year old female with baseline best corrected visual acuity
of hand motion that corresponded to 0 letters in the ETDRS chart.
• Dry AMD • IND approved in December 2010
• European CTA in preparation
• 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.
RPE Program Summary
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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• Also referred to as “Juvenile Macular Degeneration”
– Causes progressive vision loss beginning in childhood.
– Stargardt’s Disease is the most common hereditary macular dystrophy.
– Prevalence rate of about 1-in-10,000.
– Usually diagnosed in individuals under the age of twenty.
• ACT has obtained Orphan Drug Designation in United States and Europe
– 7 - 10 Years of Market Exclusivity for using RPE cells to treat Stargardt’s Disease.
Stargardt’s Macular Dystophy
Orphan Drug Opportunity with Reimbursement
80,000-100,000 patients in North America and Europe
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• AMD - estimate over 30 Million patients in North America and Europe
– The prevalence of AMD in North America in the population aged 40 to 79 years is 8.8%
– The prevalence of AMD in China in the population aged 40 to 79 years is 6.8%
• Approximately 10% of people ages 66 to 74 have symptoms of macular degeneration
• Prevalence increases to 30% in patients 75 to 85 years of age.
Dry AMD (non-exudative) – The most common form of AMD (estimates as high as 90 percent)
– No Effective Therapy Currently Available
– Estimated $20-30 Billion market
Age-Related Macular Degeneration
Potential for
Blockbuster Status
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• 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 will be monitored weekly - including high definition imaging of retina
High Definition Spectral Domain Optical Coherence Tomography (SD-OCT)
Retinal Autofluorescence
Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO)
Phase I - Clinical Trial Design
50K Cells 100K Cells 150K Cells 200K Cells
Patient 1 Patients 2/3
DSMB Review DSMB Review
Engraftment and photoreceptor activity data
available early in Phase I study.
Permit comparison of RPE and
photoreceptor activity before
and after treatment
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Phase I - Clinical Trial Update
• Prospective clinical studies to determine the safety and
tolerability of sub-retinal transplantation of hESC-derived RPE
cells.
• Vitrectomy including surgical induction of posterior vitreous
separation from the optic nerve was carried out
• Submacular injection of 50,000 hESC-derived RPE cells in a
volume of 150µl was delivered into a pre-selected area of the
pericentral macula
• Patients are monitored for systemic safety signals.
• Pre- and weekly postoperative ophthalmic examinations.
Visual acuity, fluorescein angiography, optical coherence tomography
(OCT), autofluorescence imaging and visual field testing
• DSMB Review Underway
More to come….
Early clinical and laboratory findings with respect to safety,
tolerability and engraftment to be made available
Drs. Steven Schwartz and Robert Lanza
Straight forward surgical approach
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Next 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 (DSAEK).
hESC-derived corneal
endothelium resembles
normal human corneal
endothelium
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ACT Hemangioblast
Program
Hemangioblast Program – JV Update
• Stem Cell & Regenerative Medicine International (SCRMI). – ACT and CHA agree to restructure their joint venture.
– SCRMI exclusively licensed the rights to hemangioblast program to ACT for North America and to CHA Biotech for Korea and Japan.
– SCRMI scientists reassigned to ACT to continue research and product development efforts as ACT employees
– Both companies will work to develop clinical therapies based on the joint venture's proprietary hemangioblast cell technology.
• Products Opportunities include:– Universal Blood Components, such as Red Blood Cells and Platelets
– Meschenchymal Stem Cells
• Products for treating inflammatory diseases, promoting tolerance to grafts,
repairing connective tissues, delivering therapeutic proteins, etc.
– Revascularization Therapies for treating ischemic injuries
• September 13, 2011: U.S. Patent 8,017,393 broadly covers ACT’s proprietary method for deriving hemangioblast cells from embryonic stem cells.
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Robust Product Pipeline
Hemangioblast Program: Overview
The Hemangioblast cell is a multipotent cell, and acommon precursor to hematopoietic and endothelialcells.
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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Revascularization Blood Products
Hemangioblasts RBCs
Generation of Blood Products
Hemangioblasts Enucleated
RBC’s
Capable of generating large quantities of
enucleated red blood cells.
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- Blood Replacement Products- Triage and battlefield applications
- Systemic Delivery System- Blood cells are great for transporting
materials through the body as the
entire circulatory system evolved to
facilitate their movement
- Examples: Delivery of drugs or
imaging agents
Repair of Vascular DamageHemangioblasts were tested in animal models of diabetic retinopathy,
heart disease and peripheral vascular damage
Results from treatment with
hemangioblast cells
• Restoration of blood flow to
ischemic limbs.
• Survival after myocardial infarction.
• Revascularizes ischemic retinas
Potential Impact on a Large Number of Vascular Diseases myocardial infarction, vascular ischemic damage, ischemia-reperfusion injury, diabetic vascular disease and peripheral artery disease (PAD) that are leading causes of death and/or disability worldwide.
Hemangioblasts promoted repair in peripheral vascular damage
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Platelets• Scalable: Generation of large quantities of Platelets from hESC and iPS sources
• Off-the-shelf allogeneic products: Short in vivo half-life (7 days) and allotolerance for acute uses
• Tractable regulatory approval process
• Therapeutic products for accelerating soft and hard tissue healing.
– Platelets improve the process of tissue repair – release agents involved in inflammation, angiogenesis and extracellular
matrix synthesis – all involved in wound repair
• Product Opportunties: bone fractures and bony defects; laminectomy procedures; lateral epicondylitis (i.e., tennis
elbow); total joint arthroplasty procedures (i.e., knee, hip, shoulder); plantar fasciitis; shoulder arthroscopy and
distal clavicle resection; and spinal fusion.
• Extensive Cosmetic Uses– Wrinkle and Lift Procedures: Platelets are loaded with growth factors for skin and blood vessels and produce new
collagen without the wounds of a laser and the risk of scarring
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Efficiently generate functional megakaryocytes & platelets.
• ES-derived platelets participate in clot formation.
• ES-derived platelets incorporate into mouse thrombus at site of laser-
induced arteriolar injury
Mesenchymal Stem Cells
hESC-MSCs can be
obtained using the
hemangioblast method
• hESC-MSCs are easy to derive and
can be expanded to large numbers
in vitro
• Quality controls are easier to
manage for a renewable cell source
• Can serve as an “off the shelf”
therapy, available for immediate use
• Products for treating inflammatory
diseases, promoting tolerance to
grafts, repairing connective tissues,
delivering therapeutic proteins, etc.
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Platform Technology for Generating
Robust Human Embryonic Stem Cells
Without the Need to Destroy Embryos
Single Blastomere Technology
First Proven Alternative hESC Method
• Enables Derivation of new hESC Lines via single cell biopsy
method Does not change the fate of the embryo from which the
biopsy was taken
• Utilizes single cell biopsy similar to pre-implantation genetic diagnostics
(PGD).
• Roslin Cells and ACT plan to generate GMP-compliant bank of human
ES Cells for research and commercial uses.
• Head-to-head comparison with 24 NIH lines: Average 5X more efficient
than best NIH lines for producing cells from all three germ layers.
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Single Blastomere Technology
Intellectual Property OverviewRetinal Pigment Epithelial Cells•Worldwide Patent Portfolio
•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.
Single Blastomere Technology•Worldwide Patent Filings
•Broad Claims to use of Single Blastomeres• U.S. Patent 7,893,315 broadly covers ACT’s proprietary single-blastomere technology that provides a non-destructive alternative for
deriving human embryonic stem cell (hESC) lines.
Hemangioblast Technology•Worldwide Patent Filings
•U.S. Patent 8,017,393 - Dominant Patent Position for deriving hemangioblast cells from embryonic stem cells.
Other Notables•Controlling Filings (earliest priority date) to use of OCT4 relating to induced pluripotency (iPS).
•Pending and issued patent filings directed to significant protocols for transdifferentiation.
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Financial Update – Strong Balance Sheet
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Most Stable Financial Situation In Company History
• The Company ended 2011 Q2 with $16.1 million cash on hand
• $17 million more equity available
• Virtually debt-free
• Able to pay for both U.S. clinical trials and EP clinical trial
• Significantly deepened management team (and on-going)
• Gary Rabin appointed CEO (change from interim status)
• Exciting new BoD members to announce
• Unqualified audit opinionEntering clinical trials with a
strong balance sheet
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. Matthew Vincent, Ph.D. – Director of Business Development
Edmund Mickunas – Vice President of Regulatory Affairs
Bill Douglass – Director of Corporate Communications & Social Media
Stephen Price – Interim SVP – Corporate Development
Gary Rabin – Chairman and CEO
Kathy Singh - Controller
Rita Parker – Director of Operations
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Thank you for Attending.For more information, visit www.advancedcell.com