Roth Capital 24th Annual Growth Stock Conference, Los Angeles


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Roth Capital 24th Annual Growth Stock Conference, Los Angeles

  1. 1. Leading Regenerative MedicineInvestor Presentation – March 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. Phase I - Clinical Trial Design10SMD 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.– 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 Autofluorescence50K Cells 100K Cells 150K Cells 200K CellsPatient 1 Patients 2/3DSMB Review DSMB ReviewPermit comparison of RPE andphotoreceptor activity beforeand after treatment
  11. 11. RPE Clinical Program – to date11• Dry AMD• IND approved in December 2010• European CTA in preparation• Stargardt’s (SMD) Disease• IND approved in November 2010• European CTA Approved• Orphan Drug Designation granted in U.S. and EuropeClinicalTrials.govUS: NCT01345006, NCT01344993UK: NCTO1469832
  12. 12. RPE Clinical Program – to date12Attracting Top Eye Surgeons and RetinalClinics to participate in Clinical Trials,DSMB and Scientific Advisory BoardDr. James Bainbridge, Moorfields Eye Hospital• US Clinical Trial Sites• Jules Stein Eye (UCLA)• Wills Eye Institute• Status• 2nd and 3rd SMD patients treated (Jan/Feb 2012)• Completes Cohort 1 (US)• Enrolling additional dry AMD patients• Additional Major Clinical Sites to announce• European Clinical Trial Sites• Moorfields Eye Hospital• Aberdeen Royal Infirmary• Status• 1st SMD (Europe) patient treated (20 January 2012)
  13. 13. 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 LanzaStraight forward surgical approachCan be performed on outpatient basis13
  14. 14. Surgical Overview14Autofluorescenceimages of retinas.The dark spots in theside panels show alarge area of atrophy inthe macular region.First SMD PatientFirst dry AMD Patient
  15. 15. Surgical Overview15
  16. 16. Surgical Overview16Remove gel frominner surface of retinaInjection with blebformationAir Fluid ExchangeInjection bleb formed at interface ofatrophic retina and normal retina
  17. 17. Preliminary Results17• Dry AMD• The dry AMD patient is a 77 year old female with baselineBCVA of 20/500, that corresponded to 21 letters in the ETDRS chart.• Stargardt’s (SMD) Disease• The SMD patient is a 51 year old female with baseline best corrected visual acuityof hand motion that corresponded to 0 letters in the ETDRS chart.July 12, 2011: First Patients in each trialwere treated by Dr. Steven Schwartz, M.Dat Jules Stein Eye Institute (UCLA)
  18. 18. Preliminary Results18• After surgery, structural evidenceconfirmed cells had attached andcontinued to persist during study.• No signs of hyperproliferation,abnormal growth, or immune mediatedtransplant rejection in either patient.• Anatomical evidence of hESC-RPEsurvival and engraftment.• Clinically increased pigmentation at the level of the RPE within the bedof the transplant beginning at postoperative week 1.23 January 2012Published results for first SMD andDry AMD Patients – 4 month time point
  19. 19. Preliminary Results19Recorded functional visual improvements inboth patients.• SMD Patient: Best corrected visual acuityimproved from hand motions to 20/800 andimproved from 0 to 5 letters on the ETDRSvisual acuity chart in the study eye.• Dry AMD Patient: Vision improved in thepatient with dry age-related maculardegeneration (21 ETDRS letters to 28).Six Month Follow-up:Visual acuity gains remain stable for bothpatients; SMD Patient has slight improvement.Similar trends observed for latest 3 SMD patientsSMD Patient
  20. 20. Images of hESC-RPE transplantation site in SMD Patient20pre-transplant 1wk post-op 6wk post-opColor fundus photographsWe detected clinically increased pigmentation at the level of the RPE within thebed of the transplant beginning at postoperative week 1 to month 3
  21. 21. Images of hESC-RPE transplantation site in SMD Patient21SD-OCT image collected at month 3 show survival and engraftment of hESC-RPE. Localization of the transplanted cells to the desired anatomical location.3mo post-op
  22. 22. Media Coverage22First Hints That Stem Cells CanHelp Patients Get BetterHeadline: “Stem Cell Treatment for Eye Diseases Shows Promise”Headline: “Some Promising Findings on Embryonic Stem Cells”
  23. 23. Intellectual Property – RPE ProgramDominant Patent Position for Treating Retinal Degeneration• US Patent 7,794,704 broadly cover methods for treating retinal degeneration using human RPE cells differentiated fromhuman 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 fromhuman embryonic stem cells.Coverage for RPE Cells derived from other pluripotent stem cells (including iPS cells)• Earliest priority date relates back to 2004 filings• Methods of manufacturing, use of RPE cells, and pharmaceutical formulations– e.g., source cell defined as pluripotent stem cell that expresses Oct-4, alkaline phosphatase, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81.Vigilant Filing on Improvements• Extends patent life cycle, with significance to commercialization• Include composition-of-matter claims (cell preparations, pharmaceutical preparations, etc.)• Examples: degree of pigmentation, cell density of preparation, phagocytic activity• Distinguished from adult RPE cell preparations - telomere length, A2E and lipofuscin content of cells, lack of accumulated UV damage23
  24. 24. 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 cornealendothelium24
  25. 25. Ocular Program – Hemangioblasts25The 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.
  26. 26. Ocular Program – Hemangioblasts26Hemangioblasts induce reparativeintraretinal angiogenesis is variousanimal models of ischemic retinopathies• Revascularization is observed in animalsinjected either intravitreally or intravenouslywith hESC-derived hemangioblasts• ischemia-reperfusion injury• diabetic retinopathy• GFP-labeling reveals incorporation of injectedcells into the vasculature of the eye duringangiogenesis• Hemangioblasts prevented BRB breakdown indiabetic rats.Repair of ischemic retinal vasculature in a mouseafter injection of hESC-derived hemangioblasts
  27. 27. • Generated various retinal neural progenitor cell types – or RNP cells• From both embryonic and iPS cell sources.• Discovered a new photoreceptor progenitor 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 Progenitors27hESC-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
  28. 28. Ocular Program – Mesenchymal Stromal Cells28Proprietary 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• Projected Higher Immunosuppressive Potency relative to adultMSC• 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.
  29. 29. Ocular Program – Mesenchymal Stem Cells2933,000 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 MillionManufacturing Considerations FavorhESC/Hemangioblast-derived MSC’sover Adult MSC and hESC-direct MSC
  30. 30. Platform Technology for GeneratingRobust Human Embryonic Stem CellsWithout the Need to Destroy EmbryosSingle Blastomere Technology
  31. 31. Generating hESC without Destruction of Embryo• Enables Derivation of new hESC Lines via non-destructive single cellbiopsy method• Utilizes single cell biopsy similar to pre-implantation genetic diagnostics(PGD)  Does not change the fate of the embryo from which thebiopsy was taken• Blastomere-derived hESC lines exhibited all the standard characteristics:undifferentiated proliferation, genomic stability, expression of pluripotencymarkers and the ability to differentiate into the cells of all three germ layers bothin vitro and in vivo.• Roslin Cells and ACT plan to generate GMP-compliant bank of human ES Cellsfor research and commercial uses.31Worldwide Patent FilingsIssued Broad Claims to Single Blastomere Methodology - U.S. Patent 7,893,315CONFIDENTIAL
  32. 32. iPS Platform32CONFIDENTIAL• Recipient of National Institutes of Health Directors Opportunity Award• Seminal paper identifying replicative senescence issue for vector-derived iPS cells• Feng et al. (2010) Stem Cells. 28(4):704-12.• Leading publication on protein induced iPS lines• Generated stable iPS cells from human fibroblasts by directly delivering reprogramming proteinsassociated with cell penetrating agents.• Avoids replicative senescence problem in vector-induced iPS.• Kim et al. (2009) Cell Stem Cell. 4(6):472-476.• Pending patent filings directed to protein induced iPS.Early Innovator in Pluripotency(before iPS was even a term!)• Controlling Filings (earliest priority date) to use of OCT4 for inducing pluripotencyBeats Yamanaka priority by several years
  33. 33. Financial Update – Strong Balance Sheet33Most Stable Financial Situation In Company History• The Company ended 2011 with $13.1 million cash on hand• $15 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
  34. 34. 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 Media34
  35. 35. Thank youFor more information, visit