Leading Regenerative Medicine September 2011
Jan 15, 2015
Leading Regenerative Medicine September 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 human Embryonic Stem Cells (“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 stem cells (MSC) products • Myoblast program for heart failure approved for Phase II
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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 may be part of mechanism underlying
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
RPE cell as Target
• 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
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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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Differentiation Media is Not Permissive for hESCs
Harvest for Cryopreservation
ES Cells EB
Formation RPE isolation P1 P2
0 5 weeks 12 weeks 15 weeks 18 weeks
Up to 10 percent hESC spiked No hESC’s in harvested cells
Limit of Detection for hESC 1:20,000,000 cells
RPE differentiation is the default pathway under ACT’s Patented Culture Conditions
3 weeks
EB Outgrowth
30 Weeks
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RPE Animal Safety Studies Extensive Safety Studies Shows
Lack of Tumorigenicity
Long-term data (spanning the life of the animals) revealed no evidence of teratoma formation after subretinal hESC-RPE transplantation.
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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 26 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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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 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. • Differentiate into both hematopoietic and
endothelial cell lineages – and newly discovered by ACT, mesenchymal stem cells (MSC).
• Be used to generate pathogen-free blood components
• Be used to achieve vascular repair
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Revascularization Blood Products
Hemangioblasts RBCs
Generation of Blood Products - RBC
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
Generation of Blood Products - 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
Repair of Vascular Damage Hemangioblasts 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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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
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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 Overview Retinal 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 self-fund 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 Board of Director members to announce
• Unqualified audit opinion Entering 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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