Regenerative Medicine Track at Biotech Showcase 2012, San Francisco


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Regenerative Medicine Track at Biotech Showcase 2012, San Francisco

  1. 1. Leading Regenerative MedicineRegenerative Medicine Insight Track~ Biotech Showcase - January 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. ACT Ocular Programs
  4. 4. 4Retinal 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
  5. 5. The RPE layer is critical to the function and health of photoreceptors and theretina as a whole.– RPE cells secrete trophic factors and impact on the chemical environment of thesubretinal 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 is substantial feature underlying developmentof dry-AMD, and may be involved in progression 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 (no needfor further staining) – impacts manufacturing• Small dosage vs. other therapies• The eye is generally immune-privileged site, thusminimal immunosuppression required, which may betopical.• 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 doctorsRPE cell therapy may impact over200 retinal diseases6Retinal Pigment Epithelial Cells - Rationale
  7. 7. • Established GMP-compliant process for the Reproducible Differentiationand 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 controlsand demonstrates the full transition from the hESC state.GMP ManufacturingIdeal Cell Therapy Product• Centralized Manufacturing• Small Doses that can be Frozen and Shipped• Relative Ease-of-Handling by Doctor7
  8. 8. RPE Engraftment – Mouse ModelFor each set: Panel (C) is a bright field image andPanel (D) shows immunofluorescence with anti-human bestrophin (green) and anti-humanmitochondria (red) merged and overlayed on thebright field image. Magnification 400xHuman RPE cells engraftand align with mouse RPEcells in mouse eye8
  9. 9. RPE Engraft and Function in Animal StudiesRPE treatment in animal model of retinal dystrophy has slowed thenatural progression of the disease by promoting photoreceptorsurvival.RPE cells rescued photoreceptors andslowed decline in visual acuitytreated controlPhotoreceptorlayer9
  10. 10. • 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 are monitored - including high definition imaging of retinaHigh Definition Spectral Domain Optical Coherence Tomography (SD-OCT)Retinal AutofluorescencePhase I - Clinical Trial Design50K Cells 100K Cells 150K Cells 200K CellsPatient 1 Patients 2/3DSMB Review DSMB ReviewEngraftment and photoreceptor activity dataavailable early in Phase I study.Permit comparison of RPE andphotoreceptor activity beforeand after treatment10
  11. 11. • Stargardt’s (SMD) Disease• IND approved in November 2010• European CTA Approved – enrolling patients• Orphan Drug Designation granted in U.S. and Europe• The SMD patient is a 26 year old female with baseline best corrected visual acuityof 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, thatcorresponded to 21 letters in the ETDRS chart.RPE Program SummaryJuly 12, 2011: First Patients in each trialwere treated by Dr. Steven Schwartz, M.Dat Jules Stein Eye Institute (UCLA)11
  12. 12. Surgical Overview• Prospective clinical studies to determine the safety and tolerability ofsub-retinal transplantation of hESC-derived RPE cells.• Subretinal injection of 50,000 hESC-derived RPE cells in a volume of150µl was delivered into a pre-selected area of the pericentral macula• Vitrectomy including surgical induction of posterior vitreous separationfrom the optic nerve was carried out• 25 Gauge Pars Plana Vitrectomy• Posterior Vitreous Separation (PVD Induction)• Subretinal hESC-derived RPE cells injection• Bleb Confirmation• Air Fluid ExchangeDrs. Steven Schwartz and Robert LanzaStraightforward surgical approach12
  13. 13. Surgical Overview13Autofluorescenceimages of retinas.The dark spots in theside panels show alarge area of atrophy inthe macular region.First SMD PatientFirst dry AMD Patient
  14. 14. Surgical Overview14
  15. 15. Surgical Overview15Remove gel from innersurface of retinaInjection with blebformationAir fluid exchangeInjection bleb formed atinterface of atrophicretina and normal retina
  16. 16. Ocular Program – Corneal Endothelium• More than 10 million people with corneal blindness• The cornea is the most transplanted organ (1/3 of alltransplants performed due to endothelial failure)• Solutions include the transplantation of whole cornea“Penetrating Keratoplasty” (PKP)• More popular: Transplantation of just cornealendothelium & Descemet’s membrane (DSEK/DSAEK).hESC-derived cornealendothelium resemblesnormal human cornealendothelium16
  17. 17. Ocular Program – Hemangioblasts17The Hemangioblast cell is a multipotent cell, and a commonprecursor to hematopoietic and endothelial cells.Hemangioblast cells can be used toproduce all cell types in the circulatoryand vascular systems• Hemangioblast cells can self-renew.• Hemangioblast cells can be used to achievevascular repair.• Hemangioblast activity could potentially beharnessed to treat diseases such as myocardialinfarction, stroke, cancer, vascular injury andblindness.
  18. 18. Ocular Program – Hemangioblasts18Hemangioblasts induce reparativeintraretinal angiogenesis is variousanimal models of ischemic retinopathies• Revascularization is observed in animalsinjected either intravitreally orintravenously with hESC-derivedhemangioblasts• ischemia-reperfusion injury• diabetic retinopathy• GFP-labeling reveals incorporation ofinjected cells into the vasculature of theeye during angiogenesisRepair of ischemic retinal vasculature in a mouseafter injection of hESC-derived hemangioblasts
  19. 19. • Generated various retinal neural progenitor cell types – or RNP cells• From both embryonic and iPS cell sources.• Discovered a new RNP cell type.• Tested in mouse model for retinal degeneration - ELOVL4-TG2 mice• Observed both structural and physiological consequencesAfter 2 months• ERG - increases in both the a-wave and b-wave• OCT - increases in central retinal thicknessOcular Program – Retinal Neural Progenitors19hESC-derived RNP cells reversed the progression of photoreceptordegeneration– and appeared to promote regeneration• Defined culture conditions• High yield from hESC and iPS• Homogeneous and highly purepreparations
  20. 20. Ocular Program – Mesenchymal Stromal Cells20Proprietary Large ScaleManufacturing Process forGenerating “young” MSCsfrom hESC and iPS lines• hESC-MSCs and iPS-MSCs can be expanded to largenumbers in vitro• Avoid premature senescence problem of “old” MSC’s• Superior quality controls for a renewable cell source• “Off-The-Shelf” therapy, available for immediate use• hESC-derived MSCs are HLA I+, HLA II-• MSCs can migrate to injury sites in eye – exertimmunosuppressive effects, and facilitate repair ofdamaged tissuesOcular Products in Development▫ Treating inflammatory diseases of the eye▫ Providing photoreceptor/neuron-protective activity▫ Promoting tolerance to ocular grafts and devices▫ Delivering therapeutic proteins to the eye.
  21. 21. Platform Technology for GeneratingRobust Human Embryonic Stem CellsWithout the Need to Destroy EmbryosSingle Blastomere Technology
  22. 22. First Proven Alternative hESC Method• Enables Derivation of new hESC Lines via single cell biopsymethod  Does not change the fate of the embryo from which thebiopsy was taken• Utilizes single cell biopsy similar to pre-implantation genetic diagnostics(PGD).• Roslin Cells and ACT plan to generate GMP-compliant bank of humanES Cells for research and commercial uses.• Head-to-head comparison with 24 NIH lines: Average 5X more efficientthan best NIH lines for producing cells from all three germ layers.22Single Blastomere Technology
  23. 23. Intellectual Property OverviewRetinal 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 humanembryonic 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 humanembryonic 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 forderiving 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.23
  24. 24. Financial Update – Strong Balance Sheet24Most Stable Financial Situation In Company History• The Company ended 2011 Q3 with $13.9 million cash on hand• $17 million more equity available• Virtually debt-free• Able to self-fund both U.S. clinical trials and EU clinical trial• Significantly deepened management team (and on-going)• Put in place first organizational reporting lines in ACT history• Robert Langer, Zohar Loshitzer and Greg Perry join ACT board, bringingremarkable scientific, entrepreneurial and partnering skills• One additional Board member to announce• Unqualified audit opinion Continuing clinical trials with astrong balance sheet
  25. 25. ACT Management TeamWorld Class Scientific TeamSeasoned Management TeamDr. Robert Lanza, M.D. – Chief Scientific OfficerDr. 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 DevelopmentGary Rabin – Chairman and CEOEdmund Mickunas – Vice President of Regulatory AffairsKathy Singh - ControllerRita Parker – Director of OperationsBill Douglass – Director of Corporate Communications & Social Media25
  26. 26. Thank youFor more information, visit