1. 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
1
LEADING
REGENERATIVE
MEDICINE
May 2013
2. David versus Goliath
is the story of every
emerging regenerative
medicine company in
this room….
3. 3
Structure of Retina
The Retina the light-sensitive
tissue lining the inner surface of
the eye
Retina
4. 4
Life Support to Photoreceptors
Provides nutrients and growth factors
• photoreceptors see no blood
Recycles Vitamin A
• maintains photoreceptor excitability
Detoxifies photoreceptor layer
Maintains Bruch’s Membrane
• natural antiangiogenic barrier
• immune privilege of retina
Absorbs stray light / protects from UV
RPE Layer has
multiple
critical roles
in the
health and
function
of photoreceptors and
the retina as a whole.
5. 5
Life Support to Photoreceptors
Failure of RPE cells
results in many
degenerative diseases
Stargardt’s disease
Myopic Macular Dystrophy
Age-related macular degeneration (AMD)
8. 8
RPE Therapy- Rationale
• Massive unmet medical need
• Small dosage size
– less than 200K cells
• Immune-privileged site
– minimal immunosuppression
• Ease of administration
– no separate device approval
• Unique measuring and observation environment
9. Preclinical Models
9
Injected human RPE cells
repair monolayer
structure in eye
Transplanted cells
engraft and form
correct anatomical
structure
ELOVL4 Mouse model for macular degeneration
11. GMP Process
11
Harvest for
Cryopreservation
ES Cells
EB
Formation RPE isolation P1 P2
0 5 weeks 12 weeks 15 weeks 18 weeks
TEST CASE:
• Spiked with 10 percent hESC
• No hESC’s in harvested cells
Limit of Detection for hESC
0.00008%
3 weeks
EB
Outgrowth
30 Weeks
Differentiation Media is Not
Permissive for hESCs
13. GMP Process
13
Normal female (46 XX) karyotype
of the clinical RPE lot.
Regular Marker and Karyotype
Confirmation
14. GMP Process
14
Cell potency of 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
Developed Quantitative Cell
Potency Assays
15. GMP Process
15
y = 0.0141x + 0.0007
0.00
0.50
1.00
1.50
2.00
0 20 40 60 80 100120Absorbanceat475nm
µg/mL Melanin
Pigmentation matters - optimize
time to harvest and cryopreserve
16. GMP process for differentiation and purification of RPE
– Virtually unlimited supply from stem cell source
– Optimized for manufacturing
Ideal Cell Therapy Product
– Centralized Manufacturing
– Small Doses
– Easily Frozen and Shipped
– Simple Handling by Doctor
GMP Process
16
Product Cold Chain is Easily Scaled for Global Sales
ACT Cleanroom Suite
17. Phase I - Clinical Trial Design
17
SMD and dry AMD Trials approved in U.S., SMD Trial approved in U.K.
12 Patients / trial
ascending dosages of 50K, 100K, 150K and 200K cells.
Regular Monitoring - including high definition imaging of retina
50K Cells 100K Cells 150K Cells 200K Cells
Best Vision Inclusion Criteria – First Half
SMD Trial: Hand Motion only, modified to 20/400
Dry AMD Trial: 20/800, modified to 20/400
18. 18
Participation by the leading
retinal surgeons in the world
Jules Stein
(UCLA)
Mass
Eye & Ear
Infirmary
Wills Eye
Institute
Bascom
Palmer Eye
Institute
Moorfields
Eye
Hospital
Edinburgh
Royal
Infirmary
19. Surgical Overview
19
Procedure:
• 25 Gauge Pars Plana Vitrectomy
• Posterior Vitreous Separation
• Subretinal hESC-derived RPE cells
injection
• Bleb Confirmation
• Day Surgery/Sedation only
20. Preliminary Results
20
No Adverse Events
No signs of hyperproliferation,
abnormal growth, rejection or retinal
detachment.
Persistence of cells
Anatomical evidence of hESC-RPE
survival and engraftment.
Increased pigmentation within the bed
of the transplant.
Impact on Acuity
Recorded functional visual
improvements in both patients.
21. Preliminary Results
21
Persistence of cells
Anatomical evidence of hESC-RPE
survival and engraftment.
Increased pigmentation within the bed
of the transplant.
Engraftment and Survival: SD-OCT image collected at month 3
show survival and engraftment of RPE
23. Preliminary Results
23
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).
SMD
Patient
24. Preliminary Results
24
Varying degrees of improvement in visual acuity
across patients
Some patients have pronounced gains in VA
Observed persistence of cell engraftment and
VA gains- 22 months now for initial patients
• Increased letters on ETDRS Charts
• Color perception
• Contrast
• Low light vision
These are very late stage patients with a high degree of
heterogeneity in degree of “rescue-able” photoreceptors
25. Halfway Point
25
Based on safety and functional data from first 18 patients,
FDA and MHRA have approved new 4 patient cohorts in each trial.
Best Vision Inclusion Criteria for new Cohort 2a
includes patients with vision as good as 20/100.
50K Cells 100K Cells 150K Cells 200K Cells
100K CellsFDA and MHRA Approved “Cohort 2a”
Inclusion Criteria: vision 20/100+
27. Phase II/III Projected Timeline
27
Completion of Phase I : 2013-2014
Design of Phase II/III studies is an ongoing process, but
will become more concrete during 2H2013
• Design of future studies dependent upon information
gathered throughout PI/II study
― Efficacy
― Multiple Injections
― Further evaluation of I/E criteria
― Potentially less immunosuppression
Phase II/III study commencement 2014-2015
Working with our
experts/investigators in
design of studies
28. Expanding Clinical Programs
28
Myopia creates a higher risk of permanent vision loss due
to Myopic Macular Degeneration (MMD)
• Severe near-sightedness causes elongation of the eyeball --
which can cause fissures in RPE layer.
January 2013 - FDA Approved
MMD Phase I/II study
Jules Stein Eye Institute (UCLA) and ACT
29. Price Justification
29
Unmet Therapeutic Need
Efficacy
Patient Prevalence
Pharmacoeconomics
Patient Advocacy
Pricing Justification
across all categories
of consideration
…this is what we
believe, now how will
we support this position.
30. Price Justification
30
We understand that reimbursement challenges are
increasingly becoming a central focus for new treatments
• We are working to integrate reimbursement planning early in our
RPE product life cycle
• Addressing reimbursement after market clearance doesn’t work anymore
• Design the right studies the first time…consequences are significant
• Understand payer requirements early; anticipate changes
• Evidence of value is critical; not new…just more pressure
• Value vs. alternatives
• Value to certain patient subpopulations & stakeholders
• Value vs. overall affordability (society, payer, employer & individual)
31. Reimbursement Strategy
31
Conducting a reimbursement analysis and formulating a strategy.
Working to secure meetings with CMS (Medicare) and private
insurers.
Phase II and III: Planning to gather health economics and
comparative clinical effectiveness data.
• Our design of later phases of our trials will include ability to collect and
assess pharmaco-economic data to demonstrate the cost
effectiveness and clinical effectiveness of our RPE product (relative to
existing treatments, if any approved).
Building the case for adequate reimbursement
based on a therapy’s clinical and social
benefits as part of the clinical trials is crucial.
32. Implementation
32
Activity Objectives
Document Unmet
Needs and Clinical
Value
Engaging our KOLs to help us to develop robust arguments that our
RPE cellular therapeutic approach addresses a critical need and is
“good medicine”.
Collect data on
economics of
treatment
Analyzing in detail events, activities, length of time for treatment,
timing and any other associated costs under alternative treatment
scenarios for macular degenerative diseases, particularly dry AMD.
Watching progress of clinical studies using antibodies.
Prepare stakeholder
presentations and
proposals
Documenting disease characteristics, unmet need, current disease
management practices, and measurements of economic impact
Initiate discussions with
stakeholders
Will pursue parallel discussions with CMS, key private payers, and key
treatment centers to build awareness and solicit feedback
Our Strategy during clinical trials….
33. Implementation
33
Activity Objectives
Continue discussions
with providers
We will identify and address hurdles that may remain regarding
institutional review processes and procedures in key treatment
centers – will use our KOLs as necessary.
Engage with
Foundation and Patient
Stakeholders
Develop programs to refer patients, educate patients and families,
and provide reimbursement support, as necessary.
Our Prelaunch Strategy….
34. Implementation
34
Activity Objectives
Support approval and
reimbursement
Provide on-line, phone and in the field support for patient-by-patient
product use and insurance coverage
Our Strategy Post-Launch….
We have some great role
models to follow already…
35. Intellectual Property – RPE Program
Dominant Patent Position for Treating Retinal Degeneration
• Broad Coverage for Manufacturing RPE Cells
• Broad protection of pharmaceutical preparations
Covers both RPE cell suspensions and scaffolded RPE layers.
• RPE Cells derived from other pluripotent stem cells – e.g., iPS cells
o Careful Consideration of Literal Scope
o Preservation of Doctrine of Equivalents
o Constantly Mining Existing Filings
o Vigilantly Filing on Improvements
35
Keeping our
IP Lawyers
on their toes
36. RPE Program - Investment Thesis
36
Dry AMD: More than 50 million patients in major markets.
1% market penetration
may represent $5-10B market opportunity.
Orphan indications: 10% market penetration of SMD alone may be a $100+
million/year product. Orphan status provides options for early authorization.
Immense Unmet
Medical Needs
Small Doses &
Globally Scalable Cold
Chain
Immune Privileged
Injection Site
38. 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
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
Kathy Singh - Controller
Rita Parker – Director of Operations
Dr. Matthew Vincent, Ph.D. – Director of Business Development
Bill Douglass – Dir. of Corporate Communications & Social Media
38
39. Dr. Ronald M. Green: Chairman
Dr. Judith Bernstein
Dr. Jeremy B.A. Green
Dr. Robert Kauffman
Dr. Carol A. Tauer
ACT Leadership
Gary Rabin: Chairman & CEO
Dr. Robert S. Langer, ScD: Prolific medical inventor; Chair – ACT SAB
Gregory S. Perry: EVP – Immunogen
Michael Heffernan: CEO – Collegium Pharma
Zohar Loshitzer: CEO Presbia; Founder LifeAlert Medical
Dr. Alan C. Shapiro: Renowned business school professor
39
World Class Board of Directors
Highly-regarded Ethics Advisory Board
