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 are pluripotent – can make any cell in the body.
• 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
6. 6
Life Support to Photoreceptors
Detoxifies photoreceptor layer
Maintains Bruch’s Membrane
• natural antiangiogenic barrier
• prevents abnormal blood vessel growth
• immune privilege of retina
Absorbs stray light and protects from UV
Provides critical nutrients, growth factors,
ions and water
• photoreceptors see no blood
Recycles Vitamin A
• maintains photoreceptor excitability
Function of
RPE Layer
7. 7
RPE Cells 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 address the full
range of dry AMD patients.
• Halt progression of 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.
8. RPE Engraftment and Function – Pre-clinical
8
RPE cells rescued photoreceptors and
significantly slowed lose of vision in
animal models of macular degeneration
control treated
Injected human RPE cells repair
monolayer structure in eye
Photoreceptor
layer
photoreceptor layer is
only 0 to 1 cell thick
without treatment
9. • Established GMP process for differentiation and purification of RPE
– Virtually unlimited supply from stem cell source
– Characterized to optimize performance
• Ideal Cell Therapy Product
– Centralized Manufacturing
– Small Doses
– Easily Frozen and Shipped
– Simple Handling by Doctor
GMP Manufacturing
9
Product Cold Chain is Easily Scaled for Global Sales
10. RPE Clinical Program – to date
10
World-leading eye surgeons and retinal
clinics participate in clinical trials, DSMB
and Scientific Advisory Board
ClinicalTrials.gov
US: NCT01345006, NCT01344993
UK: NCTO1469832
• US Clinical Trial Sites
• Jules Stein Eye (UCLA)
• Wills Eye Institute
• Bascom Palmer Eye Institute
• Massachusetts Eye and Ear Infirmary
Stargardts: 4 Patients Treated (Cohort 2 begun)
Dry AMD: 4 Patients Treated (Cohort 2 begun)
• European Clinical Trial Sites
• Moorfields Eye Hospital
• Edinburgh Royal Infirmary
Stargardts: 3 Patients Treated (Cohort 1 complete)
11. Surgical Overview
11
Procedure:
• 25 Gauge Pars Plana Vitrectomy
• Posterior Vitreous Separation
(PVD Induction)
• Subretinal hESC-derived RPE
cells injection
• Bleb Confirmation
• Air Fluid Exchange
12. Preliminary Results
12
• 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
13. Images of hESC-RPE transplantation site in SMD Patient
13
SD-OCT image collected at month 3 show survival and engraftment of RPE
Migration of the transplanted cells to the desired anatomical location
3mo post-op
14. Media Coverage
14
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”
15. Intellectual Property – RPE Program
• Dominant Patent Position for Treating Retinal Degeneration
• Broad Coverage for Manufacturing RPE Cells from hESC
• Coverage for RPE Cells derived from other pluripotent stem cells
(including iPS cells)
• Methods of manufacturing, use of RPE cells, and pharmaceutical formulations
• Vigilant Filing on Improvements
• Extends patent life cycle, with significance to commercialization
• Include composition-of-matter claims (cell preparations, pharmaceutical preparations, etc.)
15
16. Price Justification
16
Justification
Clinical Unmet
Need
Clinical Efficacy
Patient Prevalence
Pharmaco-
economic Data
Patient Advocacy
Groups
More
Important
Less
Important
Both private and public payers are
most interested in understanding
how new therapies will deliver
enhanced clinical value.
RPE Therapy provides pricing
justification across all categories of
consideration
17. RPE Program - Investment Thesis
17
There is an immense need for treatments against dry AMD and other
atrophic forms of macular degeneration.
• Small Doses
• Immunoprivileged – allogeneic source of cells
• Noninvasive monitoring of retina
Market potential: More than 50 million potential patients in major markets.
• Even a one percent (1%) market penetration for RPE cell therapy in dry AMD
represent a $5-10 Billion market opportunity.
• Orphan indications are also meaningful: Estimating a 10% market penetration with
reoccurring treatments every 3-5 years, Stargardt’s disease can be a $100+ million/year
product.
18. Interest from Industry
• Clear interest in ocular products by big
pharma and global biotech
• Steady developing interest in
regenerative medicine and stem cell-
derived therapeutics
Not a matter of if we will partner, but more
likely a question of when to partner
18
19. Partnering Asset Overview
• Intellectual Property
– Aggressively pursuing core patents and follow-on inventions
– Creating the “thicket behind the picket”
• Clinical Grade Cells
– RPE cells – the right cell for the task
– Master Stem Cell Bank
– Preliminary safety data
• IND package
• Our Experience!
• Clinical Trial Sites
– Knowledge leaders
19
23. Mesenchymal Stem Cells in Therapy
23
Mesenchymal stem cells (MSCs) regulate immune responses, providing
therapeutic potential for treating autoimmune or inflammatory diseases.
• MSCs can be used allogeneic: without matching between donors and recipients.
• Adult-derived MSCs have already been used therapeutically in clinical trials.
• Potential uses in a wide range of autoimmune conditions, such as multiple sclerosis, lupus, and
Crohn's disease, among others.
An "off-the-shelf" cellular drug ready for treatment of a
wide range of inflammatory and autoimmune diseases.
24. Adult Mesenchymal Stem Cells
24
Impacts on Cell Banking
• Limitation on the number of doses that can be generated from adult donors
• A few hundred to a thousand doses per cell bank per donor.
• Requires constantly creating and validating MSC banks from new donors
Impacts on Potency
• Passaging reduces immunomodulatory potency of MSC’s.
Replicative capacity is a big limitation for adult sources (bone
marrow, fat, etc) of allogeneic MSC therapies.
25. CONTRAST: hESC/iPS – derived MSC
25
Proprietary scalable
manufacturing of “young” MSCs
ACT Proprietary Process
• hESC-derived MSCs can be expanded to large numbers of cells
• Have qualities similar to fetal MSC’s
• Avoid replicative capacity problem of “old” adult MSC’s
Advantages for Manufacturing
• Use Single Master Cell Bank
• Simplifies FDA/regulatory process
• No need for finding donors
• Less labor-intensive
26. Preliminary Data
26
Animal Models testing hESC-derived MSC’s
• Substantially decrease and reverse disease conditions in autoimmune
models.
• Far more potent than adult (BM) derived MSCs.
• Have longer duration of action compared to adult (BM) derived MSCs.
Potential implications of increased potency and duration…
• Broader utility of hESC- and iPS-derived MSCs in range of diseases.
• Reduced number of cells per dose – improved safety profile.
• Longer duration between injections.
CONFIDENTIAL
28. MSC – Investment Thesis
28
The New Autoimmune/Anti-Inflammatory Medication
Autoimmune: Markets for effective treatments for
autoimmune diseases are vast.
• Forecast to exceed $80 billion by 2020
• CAGR > 10+ percent annually
Beyond Autoimmune: potent MSC therapies likely to have
utility in inflammatory disorders and chronic pain.
29. Financial Update – Strong Balance Sheet
29
• Company ended 2012 Q2 with $10 million cash on hand
• $9 million more available under existing equity line
• Virtually debt-free
• Received shareholder approval for reverse split
• Filed application for NASDAQ uplisting and have received initial comments
Other 2012 Milestones (so far)
• IRB approvals from Wills Eye Institute, Bascom Palmer Eye Hospital and Massachusetts Eye & Ear
• Initiated Europe’s first human ESC-derived transplant at Moorfields Eye Hospital
• Published first report of hESC-derived cells transplanted into humans in top medical journal, The Lancet.
• Completed Dose Cohort 1 of patients in both U.S. trials; DSMB approval to move to next higher dose
• Dosed first SMD and dry AMD patients in 100,000 cell cohorts – no AE’s observed.
30. 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
30