2012 World Stem Cell & Regenerative Medicine Congress, London

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5/21/2012

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2012 World Stem Cell & Regenerative Medicine Congress, London

  1. 1. Leading Regenerative MedicineWorld Stem Cells & Regenerative Medicine CongressMay 2012
  2. 2. 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
  3. 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 exhibit all the standard characteristics and theability to differentiate into the cells of all three germ layersboth in vitro and in vivo.• 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
  4. 4. RPE Clinical Program
  5. 5. The RPE layer is critical to the function and health of photoreceptors and theretina as a whole.– RPE cells recycle photopigments, deliver, metabolize and store vitamin A, transport ironand small molecules between retina and choroid and maintain Bruch’s membrane– RPE loss leads to photoreceptor loss and eventually blindness, such as dry-AMD– Loss of RPE layer and appears to lead to decline of Bruch’s membrane, leadingprogression from dry-AMD to wet-AMD• Discrete differentiated cell population as target• Failure of target cells results in disease progression5Retinal Pigment Epithelial Cells - RationaleRPE cell as Target
  6. 6. • Pigmented RPE cells are easy to identify – aids manufacturing• Small dosage vs. other therapies• The eye is generally immune-privileged site, thus minimalimmunosuppression required• Ease of administration, with no separate device approval andstraightforward surgical procedureRPE cell therapy may impact over 200retinal diseases6Retinal Pigment Epithelial Cells - Rationale
  7. 7. Risk: Middle-aged adults have about a 2% risk of developing AMD - the risk increases to almost 30% in adults over age 75.Expense: In 2012, the worldwide financial burden of vision loss due to AMD is estimated at >US$350 billion, with >US$250attributed to direct health care expenditures.On the Rise: Population demographics (“baby boomers”) combined with increased longevity predicts an increase of 50percent or more in the incidence rate of AMD.7The Unmet Medical NeedEarly Stage AMD(10-15M)Intermediate AMD(5-8M)Late Stage AMD(1.75M)Few Drusen DepositsSmall in sizeGeographic Atrophy: 1MCNV Occurrence: 1.2MLarge Drusen DepositsPigment ChangeGrade 0 0.5%Grade 1 3%Grade 2 9%Grade 3 27%Grade 4 43%Probability of progressionto late stage AMD within 5 yrsU.S. Patent PopulationWe process 80 percent ofall our informationthrough our eyes. AMDrepresents a huge impacton QOL in later life
  8. 8. RPE Engraftment and Function – Pre-clinicalHuman RPE cells engraftand align with mouse RPEcells in mouse eye8treatedRPE cells rescuedphotoreceptors andslowed decline in acuityin RCS ratcontroltreated
  9. 9. • Established GMP process for differentiation and purification of RPE– Virtually unlimited supply– Pathogen-free GMP conditions– Minimal batch-to-batch variation– Characterized to optimize performance– Virtually identical expression of RPE-specific genes to controlsGMP ManufacturingIdeal Cell Therapy Product• Centralized Manufacturing• Small Doses• Easily Frozen and Shipped• Simple Handling by Doctor9
  10. 10. Characterizing Clinical RPE Lots10Normal female (46 XX) karyotypeof the clinical RPE lot.Up-regulation of RPE markers anddown-regulation of hESC markers
  11. 11. Characterizing Clinical RPE Lots11Quantitative Potency AssayEach lot is assessed by phagocytosis (criticalfunction in vivo) of fluorogenic bioparticles.Flow cytometry histogram showingphagocytosis of pHrodo bioparticles4°C 37°C
  12. 12. Effects of Pigmentation12Melanin content can be measured spectrophotometrically and used to determine theoptimal time to harvest and cryopreserve RPE.y = 0.0141x + 0.00070.000.501.001.502.000 20 40 60 80 100120Absorbanceat475nmµg/mL Melanin
  13. 13. Phase I - Clinical Trial Design13SMD and dry AMD Trials approved in U.S., SMD Trial approved in U.K.• 12 Patients for each trial, ascending dosages of 50K, 100K, 150K and 200K cells.• Patients are monitored - including high definition imaging of retinaHigh Definition Spectral Domain Optical Coherence Tomography (SD-OCT)Retinal Autofluorescence50K Cells 100K Cells 150K Cells 200K CellsPatient 1 Patients 2/3DSMB Review DSMB ReviewRPE and photoreceptor activitycompared before and after surgery
  14. 14. Phase I – Endpoints14PRIMARY ENDPOINTS:Safety Assessment acceptable, in the absence of: Adverse event related to cell product Any contamination with an infectious agent Cells exhibiting tumorigenic potentialSECONDARYENDPOINTSSuccessful engraftment via: OCT, fundus and other similar imaging evidence ERG showing enhanced activityEvidence of rejection: Imaging evidence that cells are no longer in the correct location ERG showing that activity has returned to pre-transplant conditions
  15. 15. RPE Clinical Program – to date15World-leading eye surgeons and retinalclinics participate in clinical trials, DSMBand Scientific Advisory Board• US Clinical Trial Sites• Jules Stein Eye (UCLA)• Wills Eye Institute• Bascom Palmer Eye Institute• Massachusetts Eye and Ear Infirmary• Stargardts: 1st cohort complete, cleared to treat next cohort• Dry AMD: 1st cohort complete, will submit data on patients 2& 3 to DSMB in late May• European Clinical Trial Sites• Moorfields Eye Hospital• Aberdeen Royal Infirmary• 1st SMD patient treated, about to treat patients 2 & 3ClinicalTrials.govUS: NCT01345006, NCT01344993UK: NCTO1469832
  16. 16. Surgical Overview16Drs. Steven Schwartz and Robert Lanza• Subretinal injection of 50,000 RPE cells in a volume of150µl delivered into a pre-selected area of thepericentral macula• Procedure:• 25 Gauge Pars Plana Vitrectomy• Posterior Vitreous Separation (PVD Induction)• Subretinal hESC-derived RPE cells injection• Bleb Confirmation• Air Fluid ExchangeStraight-forward surgery that is performedon outpatient basis
  17. 17. Preliminary Results17• 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
  18. 18. Preliminary Results18Recorded functional visual improvements in both patients.• SMD Patient: BCVA improved from hand motions to 20/800 and improved from 0 to 5letters on the ETDRS visual acuity chart• Dry AMD Patient: Vision improved in the patient with dry age-related maculardegeneration (21 ETDRS letters to 28)• Nine Month Follow-up:• Visual acuity gains remain stable for both patients; SMD Patient continues toshow improvement.• Similar trends observed for latest AMD and SMD patients• Update on U.K. SMD01 Patient (3 month follow-up)• ETDRS: Improved from 5 letters to 10 letters• Subjective: Reports significantly improved ability to read text on TV
  19. 19. Images of hESC-RPE transplantation site in SMD Patient19pre-transplant 1wk post-op 6wk post-opColor fundus photographsClinically increased pigmentation within the bed of the transplant
  20. 20. Images of hESC-RPE transplantation site in SMD Patient20SD-OCT image collected at month 3 show survival and engraftment of RPE Migration of the transplanted cells to the desired anatomical location3mo post-op
  21. 21. Phase II/III Design21• Design of future studies dependent upon information gathered throughout PI/IIstudy• Efficacy• Patient population less VA impact 20/200?• Multiple Injections• Sub macular Injections• Further evaluation of I/E criteria• Potentially less immunosuppression• Other considerations of efficacy:• New or more sensitive technologies• Possible saline placebo injection (same eye)Working with ourexperts/investigators indesign of studies
  22. 22. RPE Cells – Additional Indications22• Myopic Macular Dystrophy (MMD)• Retinopathy of Prematurity• Angioid Streaks• Retinitis Pigmentosa• Bests Disease (vitelliform macular dystrophy)• Multifocal Choroidopathy SyndromesCombination Products• Combined with other cell types (photoreceptor progenitors)• Combined with anti-angiogenic agents, neuroprotective agents, etc.
  23. 23. Therapeutic Pipeline -Ocular Programs
  24. 24. 24Retinal Pigment Epithelial Cells Macular Degeneration - dry AMD, Stargardt’s Disease, MMD Retinitis Pigmentosa Photoreceptor protectionHemangioblast cells Ischemic retinopathy– diabetic retinopathy, vascular occlusionsRetinal Neural Progenitor cellsIsolated Protective Factors Photoreceptor Loss, Modulation of Müller Cells Protection of Retinal Ganglion cells (Glaucoma)Corneal Endothelium, Corneal Epithelium,Descemet’s Membrane Corneal DiseaseMesenchymal Stromal Cells Glaucoma, Uveitis Retinitis Pigmentosa Management of Ocular SurfaceslightretinaRPElayerPhotoreceptors
  25. 25. ACT MSC Program
  26. 26. Ocular Program –26Proprietary scaledmanufacturing for generating“young” MSCs from hESCand iPS lines• hESC-and IPS-MSCs are expanded to large numbers in vitro• Avoid senescence problem of “old” MSC’s• Renewable cell source and “Off-The-Shelf” therapy• hESC-derived MSCs are HLA I+, HLA II-• Higher immunosuppressive potency relative to adult MSC• MSCs can migrate to injury sites in eye, exert localimmunosuppressive effects, and repair damaged tissueOcular Products in Development▫ Inflammatory diseases of the eye▫ Photoreceptor/neuron-protective activity▫ Tolerance to ocular grafts and devices▫ Delivering therapeutic proteins to the eye
  27. 27. Mesenchymal SCs – Hemangioblast Derived2733,000 units MSCs from hESC-MSCs1 unit MSCsfrom adult BMCompared to Adult MSC• Less labor-intensive• Single Bank Regulatory ProcessNo need to derive new banksQuality controls are easier to manage• Larger yield of MSCsCompared to hESC-direct• Less labor-intensive• Larger yield of MSCs• Faster acquisition of markershESC Direct HB MethodStart 350,000 ESC 200,000 EB’sCollect 48 days 44 daysYield 4 Million 85 MillionStrongly advantageous to derive MSCsfrom our hESC/HB method vs adult orhESC-direct MSC
  28. 28. 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 Media28
  29. 29. Thank youFor more information, visit www.advancedcell.com

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