Leading Regenerative MedicineRodman & Renshaw Global Investment ConferenceSeptember 2012
This presentation is intended to present a summary of ACT’s (“ACT”, or “Advanced CellTechnology Inc”, or “the Company”) salient business characteristics.The information herein contains “forward-looking statements” as defined under the federalsecurities laws. Actual results could vary materially. Factors that could cause actual resultsto 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 fromtime to time with the Securities and Exchange Commission. The risks identified therein, aswell as others not identified by the Company, could cause the Company’s actual results todiffer materially from those expressed in any forward-looking statements. Ropes GrayCautionary Statement Concerning Forward-Looking Statements2
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 Directors 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 pluripotency3Final Product Definition: hESC-derivedproducts will be manufactured using a cellline made in 2005 from single cell isolatedwithout the destruction of any embryos
6Life 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 excitabilityFunction ofRPE Layer
7RPE Cells TherapyEarly Stage AMD(10-15M)Intermediate AMD(5-8M)Late Stage AMD(1.75M)U.S. Patient PopulationACT’s RPE Cell Therapy should address the fullrange of dry AMD patients.• Halt progression of vision loss in early stagepatients• Restore some visual acuity in later stagepatientsDry AMD represents more than 90 percent of allcases of AMDNorth America and Europe alone have more than30 Million dry AMD patients who should beeligible for our RPE cell therapyOn the Rise: Population demographics(“baby boomers”) combined with increasedlongevity predicts an increase of 50 percentor more in the incidence rate of AMD.
RPE Engraftment and Function – Pre-clinical8RPE cells rescued photoreceptors andsignificantly slowed lose of vision inanimal models of macular degenerationcontrol treatedInjected human RPE cells repairmonolayer structure in eyePhotoreceptorlayerphotoreceptor layer isonly 0 to 1 cell thickwithout treatment
• 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 DoctorGMP Manufacturing9Product Cold Chain is Easily Scaled for Global Sales
RPE Clinical Program – to date10World-leading eye surgeons and retinalclinics participate in clinical trials, DSMBand Scientific Advisory BoardClinicalTrials.govUS: NCT01345006, NCT01344993UK: NCTO1469832• US Clinical Trial Sites• Jules Stein Eye (UCLA)• Wills Eye Institute• Bascom Palmer Eye Institute• Massachusetts Eye and Ear InfirmaryStargardts: 4 Patients Treated (Cohort 2 begun)Dry AMD: 4 Patients Treated (Cohort 2 begun)• European Clinical Trial Sites• Moorfields Eye Hospital• Edinburgh Royal InfirmaryStargardts: 3 Patients Treated (Cohort 1 complete)
Surgical Overview11Procedure:• 25 Gauge Pars Plana Vitrectomy• Posterior Vitreous Separation(PVD Induction)• Subretinal hESC-derived RPEcells injection• Bleb Confirmation• Air Fluid Exchange
Preliminary Results12• Structural evidence confirmed cells hadattached and persisted• No signs of hyperproliferation,abnormal growth, or rejection• Anatomical evidence of hESC-RPEsurvival and engraftment.• Clinically increased pigmentationwithin the bed of the transplant• Recorded functional visualimprovements in both patients
Images of hESC-RPE transplantation site in SMD Patient13SD-OCT image collected at month 3 show survival and engraftment of RPE Migration of the transplanted cells to the desired anatomical location3mo post-op
Media Coverage14First Hints That Stem Cells CanHelp Patients Get BetterHeadline: “Stem Cell Treatment for Eye Diseases Shows Promise”Headline: “Some Promising Findings on Embryonic Stem Cells”
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
Price Justification16JustificationClinical UnmetNeedClinical EfficacyPatient PrevalencePharmaco-economic DataPatient AdvocacyGroupsMoreImportantLessImportantBoth private and public payers aremost interested in understandinghow new therapies will deliverenhanced clinical value.RPE Therapy provides pricingjustification across all categories ofconsideration
RPE Program - Investment Thesis17There is an immense need for treatments against dry AMD and otheratrophic forms of macular degeneration.• Small Doses• Immunoprivileged – allogeneic source of cells• Noninvasive monitoring of retinaMarket potential: More than 50 million potential patients in major markets.• Even a one percent (1%) market penetration for RPE cell therapy in dry AMDrepresent a $5-10 Billion market opportunity.• Orphan indications are also meaningful: Estimating a 10% market penetration withreoccurring treatments every 3-5 years, Stargardt’s disease can be a $100+ million/yearproduct.
Interest from Industry• Clear interest in ocular products by bigpharma and global biotech• Steady developing interest inregenerative medicine and stem cell-derived therapeuticsNot a matter of if we will partner, but morelikely a question of when to partner18
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 leaders19
Mesenchymal Stem Cells in Therapy23Mesenchymal stem cells (MSCs) regulate immune responses, providingtherapeutic 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, andCrohns disease, among others.An "off-the-shelf" cellular drug ready for treatment of awide range of inflammatory and autoimmune diseases.
Adult Mesenchymal Stem Cells24Impacts 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 donorsImpacts on Potency• Passaging reduces immunomodulatory potency of MSC’s.Replicative capacity is a big limitation for adult sources (bonemarrow, fat, etc) of allogeneic MSC therapies.
CONTRAST: hESC/iPS – derived MSC25Proprietary scalablemanufacturing of “young” MSCsACT 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’sAdvantages for Manufacturing• Use Single Master Cell Bank• Simplifies FDA/regulatory process• No need for finding donors• Less labor-intensive
Preliminary Data26Animal Models testing hESC-derived MSC’s• Substantially decrease and reverse disease conditions in autoimmunemodels.• 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
MSC – Investment Thesis28The New Autoimmune/Anti-Inflammatory MedicationAutoimmune: Markets for effective treatments forautoimmune diseases are vast.• Forecast to exceed $80 billion by 2020• CAGR > 10+ percent annuallyBeyond Autoimmune: potent MSC therapies likely to haveutility in inflammatory disorders and chronic pain.
Financial Update – Strong Balance Sheet29• 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 commentsOther 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.
ACT Management TeamHighly Experienced and Tightly Integrated Management TeamGary Rabin – Chairman & CEODr. Robert Lanza, M.D. – Chief Scientific OfficerEdmund Mickunas – Vice President of Regulatory AffairsKathy Singh - ControllerRita Parker – Director of OperationsDr. Irina Klimanskaya, Ph.D. – Director of Stem Cell BiologyDr. Shi-Jiang (John) Lu, Ph.D. – Senior Director of ResearchDr. Roger Gay, Ph.D. - Senior Director of ManufacturingDr. Matthew Vincent, Ph.D. – Director of Business DevelopmentBill Douglass – Director of Corporate Communications & Social Media30
Thank youFor more information, visit www.advancedcell.com