January 2013LEADINGREGENERATIVEMEDICINE
This presentation is intended to present a summary of ACT’s (“ACT”, or “Advanced CellTechnology Inc”, or “the Company”) sa...
ACT is a publicly-traded biotechnology company• Develop cellular therapies for the treatment of diseases and conditionstha...
Multiple Pluripotent Cell PlatformsSingle Blastomere-derivedEmbryonic Stem Cell LinesGenerating hESC linesWITHOUT DESTRUCT...
Multiple Pluripotent Cell PlatformsInduced Pluripotency Stem Cells (iPS)• Early Innovator in Pluripotency(before iPS was e...
RPE Clinical Program
7Structure of RetinaThe Retina the light-sensitivetissue lining the inner surface ofthe eyeRetina
8Life Support to PhotoreceptorsProvides nutrients and growth factors• photoreceptors see no bloodRecycles Vitamin A• maint...
9Life Support to PhotoreceptorsLoss of RPE cellsBuild up of toxic wasteLoss of photoreceptorsDry AMDBruch’s Mem. dehiscenc...
10RPE Therapy- RationaleDry AMDrepresents more than90%of all cases of AMDNorth America & Europealone have more than 30 mil...
RPE cell therapy may impactover 200 retinal diseases11RPE Therapy- Rationale• Massive unmet medical need• Unique measuring...
12RPE Therapy- RationaleU.S. PATIENT POPULATIONEARLY STAGE(10-15M)INTERMEDIATE(5-8M)LATE STAGE(1.75M)ACT’S RPE Cell Therap...
GMP process for differentiation and purification of RPE– Virtually unlimited supply from stem cell source– Optimized for m...
Preclinical - Examples14control treatedInjected human RPE cellsrepair monolayer structure ineyePhotoreceptorlayerphotorece...
Phase I - Clinical Trial Design15SMD and dry AMD Trials approved in U.S., SMD Trial approved in U.K.12 Patients / trialasc...
Participating Retinal Surgeons16Steven D. Schwartz, MDChief, Retina DivisionAhmanson Professor of OphthalmologyDirector, D...
Participating Retinal Surgeons17Dean Eliott, MDAssociate Director, Retina ServiceProfessor, Harvard Medical SchoolMassachu...
Surgical Overview18Procedure:• 25 Gauge Pars PlanaVitrectomy• Posterior Vitreous Separation(PVD Induction)• Subretinal hES...
Preliminary Results19No Adverse EventsNo signs of hyperproliferation,abnormal growth, rejection or retinaldetachment.Persi...
20Engraftment and Survival: SD-OCT image collected at month 3show survival and engraftment of RPESMD0013mo post-opPrelimin...
21BaselineInjection siteMonth 1 Month 2SMD PATIENT UK04
22BaselineInjection siteMonth 1 Month 3SMD PATIENT UK03
23Baseline 2 monthsDRY AMD PATIENT 204
Preliminary Results – Functional24Visual Acuity Measurements• SMD Patient: BCVA improved from hand motions to 20/800 andim...
Current Safety Profile – Stargardt’s Trial2512 SMD Patients Treated3 patients (50K cells cohort) treated – US Trial > Coho...
Current Safety Profile – Dry AMD Trial266 dry AMD Patients Treated3 patients (50K cells cohort) treated > Cohort Complete3...
RPE Program Milestone Objectives27Key upcoming milestones• Continue to treat and review patient data• Define efficacy endp...
Intellectual Property – RPE ProgramTreatment Dominant Patent Position for Treating RetinalDegenerationManufacturing Broad ...
Price Justification29Unmet Therapeutic NeedEfficacyPatient PrevalencePharmacoeconomicsPatient AdvocacyPricing Justificatio...
RPE Program - Investment Thesis30• Immense unmet medical need• Small Doses• Immunoprivileged – permits central (allogeneic...
Therapeutic Pipeline -Ocular Programs
Retinal Pigment Epithelial Cells Macular Degeneration - dry AMD Retinitis Pigmentosa Photoreceptor protectionHemangiobl...
Mesenchymal Stem CellProgram33
Mesenchymal Stem Cells in Therapy34Mesenchymal stem cells (MSCs) regulate immune responsesprovide therapeutic potential fo...
hESC- and iPS – derived MSC35ACT Proprietary Process• hESC- and iPS-derived MSCs• virtually inexhaustible source of starti...
Potential applications36• >100 autoimmune diseases• Multiple Sclerosis• Osteoarthritis• Crohn’s Disease/IBS• Aplastic Anem...
ACTBlood ComponentsProgram
Hemangioblast Program: Overview38Hemangioblast: common precursor to hematopoietic and endothelial cells.Multipotent cell p...
Generation of Blood Products39Hemangioblasts RBCsHemangioblasts EnucleatedRBC’sProcess generates largequantities of functi...
The Case for Platelets40Platelets are key elements ofhemostasis and thrombosis as well astissue regeneration after injury ...
The Case for Platelets41Donor-derived platelets raise concerns:• variability of quality and quantity• risk of infectious t...
Platelets 2.042Ability to control platelet manufacturing providesopportunities to improve storage, fine tuneplatelets for ...
Platelet Production Stages43Stem CellPromegakaryoblastmegakaryoblastPromegakaryocytePFC: ProplateletFormation CellPlatelet...
Size and Polyploidy44Average size (diameter) of cellsat the beginning and 6 days after MK cultureDNA ploidy analysis by fl...
Platelets45Bone MarrowLimited By Source Infinite SupplyCord Blood hESC
Representative iPS-platelet prep46Blood platelets iPS plateletsCD42bCD41a
Achieving Function and Scale47• Ultrastructural and morphological features of SC-derived platelets areindistinguishable fr...
Activation48iPS-PLT’s display appropriatecytoskeletal functionin glass spreading assays.
Characterization of Platelets49hESC- and iPS-derived platelets participatein clot formation and retraction
Clinical Program Status50• Animal model studies showproper in vivo function• Achieved clinical dosescale manufacturing• Co...
ACT Corporate Overview
Financial Update – Strong Balance Sheet52• Company ended 2012 Q3 with $42 million in cash oravailability of cash through f...
ACT Management TeamHighly Experienced and Tightly Integrated Management TeamGary Rabin – Chairman & CEODr. Robert Lanza, M...
Dr. Ronald M. Green: ChairmanDr. Judith BernsteinDr. Jeremy B.A. GreenDr. Robert KauffmanDr. Carol A. TauerACT LeadershipG...
Thank youFor more information, visit www.advancedcell.com
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Biotech Showcase, San Francisco, Calif., Jan. 8, 2013

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Biotech Showcase, San Francisco, Calif., Jan. 8, 2013

  1. 1. January 2013LEADINGREGENERATIVEMEDICINE
  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 is a publicly-traded biotechnology company• Develop cellular therapies for the treatment of diseases and conditionsthat impact hundreds of millions of people worldwide• Premier scientific and research development team• Cell therapies are traditionally derided for being high cost, high touchand having lack of scalability. Not our approach at all>> Centralized, Scalable, Cost Effective Cell Therapy Products <<About ACT:– Ticker – ACTC– Market Capitalization: $160 million– Principal lab and GMP facility: Marlborough, MA– Corporate HQ: Santa Monica, CA– Only hESC-derived tissue trials ongoing worldwide3Company Overview
  4. 4. Multiple Pluripotent Cell PlatformsSingle Blastomere-derivedEmbryonic Stem Cell LinesGenerating hESC linesWITHOUT DESTRUCTION OF EMBRYOUtilizes aSINGLE CELL BIOPSYACT never needs to make another hESC line again4Final Product Definition: hESC-derivedproducts will be manufactured usinga cell line made in 2005 from singlecell isolated without the destructionof any embryos
  5. 5. Multiple Pluripotent Cell PlatformsInduced Pluripotency Stem Cells (iPS)• Early Innovator in Pluripotency(before iPS was even a term!)• Controlling Patent Filings (earliest priority date)to use of OCT4 for inducing pluripotency• Science is moving quickly, butRegulatory Agencies (FDA, EMA)proceeding carefully• ACT pursuing platelets as firstiPS-derived product(cell fragments – no nucleus,not mitotically active)5
  6. 6. RPE Clinical Program
  7. 7. 7Structure of RetinaThe Retina the light-sensitivetissue lining the inner surface ofthe eyeRetina
  8. 8. 8Life Support to PhotoreceptorsProvides nutrients and growth factors• photoreceptors see no bloodRecycles Vitamin A• maintains photoreceptor excitabilityDetoxifies photoreceptor layerMaintains Bruch’s Membrane• natural antiangiogenic barrier• immune privilege of retinaAbsorbs stray light / protects from UVRPE Layer hasmultiplecritical rolesin thehealth andfunctionof photoreceptors andthe retina as a whole.
  9. 9. 9Life Support to PhotoreceptorsLoss of RPE cellsBuild up of toxic wasteLoss of photoreceptorsDry AMDBruch’s Mem. dehiscenceChoroidal neovascularizationWet AMD
  10. 10. 10RPE Therapy- RationaleDry AMDrepresents more than90%of all cases of AMDNorth America & Europealone have more than 30 million dry AMD patientswho should be eligible for our RPE cell therapyWhat if we couldreplacemissing RPE cells?
  11. 11. RPE cell therapy may impactover 200 retinal diseases11RPE Therapy- Rationale• Massive unmet medical need• Unique measuring and observation environment• Easy to identify – aids manufacturing• Small dosage size – less than 200K cells• Immune-privileged site - minimal/no immunosuppression• Ease of administration - no separate device approval
  12. 12. 12RPE Therapy- RationaleU.S. PATIENT POPULATIONEARLY STAGE(10-15M)INTERMEDIATE(5-8M)LATE STAGE(1.75M)ACT’S RPE Cell Therapyshould address the full rangeof dry AMD patients:Halt progression of vision loss in earlystage patientsRestore some visual acuity in laterstage patients
  13. 13. GMP process for differentiation and purification of RPE– Virtually unlimited supply from stem cell source– Optimized for manufacturingIdeal Cell Therapy Product– Centralized Manufacturing– Small Doses– Easily Frozen and Shipped– Simple Handling by DoctorGMP Manufacturing13Product Cold Chain is Easily Scaled for Global Sales
  14. 14. Preclinical - Examples14control treatedInjected human RPE cellsrepair monolayer structure ineyePhotoreceptorlayerphotoreceptor layeris only 0 to 1 cellthick withouttreatment
  15. 15. Phase I - Clinical Trial Design15SMD and dry AMD Trials approved in U.S., SMD Trial approved in U.K.12 Patients / trialascending dosages of 50K, 100K, 150K and 200K cells.Regular Monitoring - including high definition imaging of retina50K Cells 100K Cells 150K Cells 200K CellsPatient 1 Patients 2/3DSMB Review DSMB Review
  16. 16. Participating Retinal Surgeons16Steven D. Schwartz, MDChief, Retina DivisionAhmanson Professor of OphthalmologyDirector, Diabetic Eye Disease and Retinal Vascular CenterDirector, Ophthalmic Photography Clinical LaboratoryJules Stein Eye InstituteWills Eye InstituteCarl D. Regillo, MDDirector, Retina ServiceProfessor of Ophthalmology, Jefferson Medical CollegeByron L. Lam, MDDirector, Clinical Visual PhysiologyProfessor of OphthalmologyBascom Palmer Eye Institute
  17. 17. Participating Retinal Surgeons17Dean Eliott, MDAssociate Director, Retina ServiceProfessor, Harvard Medical SchoolMassachusetts Eye and Ear InfirmaryMoorfields Eye HospitalJames Bainbridge, MA MB BChir PhD FRCOphthProfessor of Retinal Studies, UCL Institute of OphthalmologyPhilip J. Rosenfeld, MD PhDProfessor of OphthalmologyBascom Palmer Eye InstituteEdinburgh Royal InfirmaryBaljean Dhillon BMed Sci, BM BS, FRCSSurgeon, Edinburgh Royal InfirmarySurgeon, Lothian University Hospitals NHS TrustProfessor of Ophthalmology, University of EdinburghProfessor of Visual Impairment Studies, Heriot Watt University
  18. 18. Surgical Overview18Procedure:• 25 Gauge Pars PlanaVitrectomy• Posterior Vitreous Separation(PVD Induction)• Subretinal hESC-derived RPEcells injection• Bleb Confirmation• Air Fluid Exchange
  19. 19. Preliminary Results19No Adverse EventsNo signs of hyperproliferation,abnormal growth, rejection or retinaldetachment.Persistence of cellsAnatomical evidence of hESC-RPEsurvival and engraftment.Increased pigmentation within the bedof the transplant.Impact on AcuityRecorded functional visualimprovements in both patients.
  20. 20. 20Engraftment and Survival: SD-OCT image collected at month 3show survival and engraftment of RPESMD0013mo post-opPreliminary Results – Structural
  21. 21. 21BaselineInjection siteMonth 1 Month 2SMD PATIENT UK04
  22. 22. 22BaselineInjection siteMonth 1 Month 3SMD PATIENT UK03
  23. 23. 23Baseline 2 monthsDRY AMD PATIENT 204
  24. 24. Preliminary Results – Functional24Visual Acuity Measurements• SMD Patient: BCVA improved from hand motions to 20/800 andimproved from 0 to 5 letters on the ETDRS visual acuity chart• Dry AMD Patient: Vision improved in the patient with dry age-related macular degeneration (21 ETDRS letters to 28)14 month Follow-up:• Visual acuity gains remain relatively stable for both patients• SMD Patient continues to show improvement.U.K. SMD01 Patient (at 9 month follow-up)• ETDRS: Improved from 5 letters to 10 letters, and stable• Subjective: Reports significantly improved ability to read text on TV
  25. 25. Current Safety Profile – Stargardt’s Trial2512 SMD Patients Treated3 patients (50K cells cohort) treated – US Trial > Cohort Complete3 patients (50K cells cohort) treated – UK Trial > Cohort Complete3 patient (100K cells cohort) treated – US Trial > Cohort Complete3 patient (100K cells cohort) treated – UK Trial > Cohort CompleteNo reports of any adverse events or complications due tocells per se• No evidence of inflammation or infiltration• No evidence of ectopic tissue formation• No evidence of retinal detachment
  26. 26. Current Safety Profile – Dry AMD Trial266 dry AMD Patients Treated3 patients (50K cells cohort) treated > Cohort Complete3 patient (100K cells cohort) treated > Cohort CompleteNo reports of any adverse events or complications due tocells per se• No evidence of inflammation or infiltration• No evidence of ectopic tissue formation• No evidence of retinal detachment
  27. 27. RPE Program Milestone Objectives27Key upcoming milestones• Continue to treat and review patient data• Define efficacy endpoints and targeted patient visualcriteria• Treat earlier stage disease to determine curativepower of dissociated cell injections• Simplify shipping and cell-prep to enhance scaleddistribution platform
  28. 28. Intellectual Property – RPE ProgramTreatment Dominant Patent Position for Treating RetinalDegenerationManufacturing Broad Coverage for Manufacturing RPE Cells from hESCPreparations Claims directed to pharmaceutical preparations of RPECells from hESC, including both cell suspensions andscaffolded RPE layers.Sources Issued patents cover RPE Cells derived from otherpluripotent stem cells (including iPS cells)Vigilance Regularly Filing on Improvements• Extend patent life cycle, with significance to commercialization• Include composition-of-matter claims (cell preparations,pharmaceutical preparations, etc.)28
  29. 29. Price Justification29Unmet Therapeutic NeedEfficacyPatient PrevalencePharmacoeconomicsPatient AdvocacyPricing Justificationacross all categoriesof consideration
  30. 30. RPE Program - Investment Thesis30• Immense unmet medical need• Small Doses• Immunoprivileged – permits central (allogeneic) source of cells• Noninvasive monitoring of retinaMarket potential: More than 50 million patients in major markets.1% market penetration may represent $5-10B market opportunity.Orphan indications are meaningful: Estimating a 10% market penetrationwith reoccurring treatments every 3-5 years, Stargardt’s disease can be a$100+ million/year product.
  31. 31. Therapeutic Pipeline -Ocular Programs
  32. 32. Retinal Pigment Epithelial Cells Macular Degeneration - dry AMD 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 Surfaces32Retina
  33. 33. Mesenchymal Stem CellProgram33
  34. 34. Mesenchymal Stem Cells in Therapy34Mesenchymal stem cells (MSCs) regulate immune responsesprovide therapeutic potential for treating autoimmune orinflammatory diseases.• Allogeneic - without HLA matching.• Track Record - Adult-derived MSCs already in 200+ clinical trials.Derived from Bone Marrow and Adipost TissueHowever, allogeneic adult-derived MSC’s are limitedby replicative senescence, and as it turns out, a relativelack of potency
  35. 35. hESC- and iPS – derived MSC35ACT Proprietary Process• hESC- and iPS-derived MSCs• virtually inexhaustible source of starting material• replicative capacity is more than 33,000 times greaterAdvantages for Manufacturing• Use Single Master Cell Bank• Simplifies FDA/regulatory process• No need for continually finding and qualifyingdonors• Less labor-intensive
  36. 36. Potential applications36• >100 autoimmune diseases• Multiple Sclerosis• Osteoarthritis• Crohn’s Disease/IBS• Aplastic Anemia• Chronic Pain• Limb Ischemia• Heart Failure/MI• Stroke• Graft-versus-host Disease• Spinal Cord Injury• Parkinson’s Disease• Liver Cirrhosis• Emphysema/Pulmonary Diseases• Wound healing(ulcers/decubitus/burns)• HSC engraftment/irradiatedcancer patients• Eye diseases (uveitis, retinaldegeneration, glaucoma)
  37. 37. ACTBlood ComponentsProgram
  38. 38. Hemangioblast Program: Overview38Hemangioblast: common precursor to hematopoietic and endothelial cells.Multipotent cell produces allcell types in the circulatory andvascular systems
  39. 39. Generation of Blood Products39Hemangioblasts RBCsHemangioblasts EnucleatedRBC’sProcess generates largequantities of functionalred blood cellsandmegakaryocytes &platelets
  40. 40. The Case for Platelets40Platelets are key elements ofhemostasis and thrombosis as well astissue regeneration after injury or surgery.• Maintain vascular integrity and play vital roles in wound repair• Thrombocytopenia is a major cause of morbidity in sepsis,cancer and preeclampsia• Used regularly in soft- and hard-tissue applications in most fieldsof surgery..Beyond Donor Supply: Estimatedemand for additional 1-2M units/year
  41. 41. The Case for Platelets41Donor-derived platelets raise concerns:• variability of quality and quantity• risk of infectious transmission• short lifespan of stored platelets• bacterial contamination during storage• development of alloantibodies in multi-transfused patientsPlatelets are the blood product most difficult tomaintain without unnecessary wastage.• Platelets do not tolerate refrigeration.• Storage at room temperature is limited to 5–7 daysNeed for new strategiesto generate plateletsfor infusion therapy.
  42. 42. Platelets 2.042Ability to control platelet manufacturing providesopportunities to improve storage, fine tuneplatelets for use in wound healing applications, as wellas to engineer new roles for platelets beyondtraditional involvement in wound healing.• Improve cryopreservation of platelets• Make lyophilization of platelets tractable solution• Utilize platelets for drug delivery• Utilize platelets in imaging (load with contrast agents)CONFIDENTIAL - BUSINESS PROPRIETARY
  43. 43. Platelet Production Stages43Stem CellPromegakaryoblastmegakaryoblastPromegakaryocytePFC: ProplateletFormation CellPlateletsStage I Stage II Stage IIIStage IVCFU-GEMM BFU-MK CFU-MKendomitosis
  44. 44. Size and Polyploidy44Average size (diameter) of cellsat the beginning and 6 days after MK cultureDNA ploidy analysis by flow cytometry of CD41a+ cells.DNA ploidy up to 32N was observed in these cells.
  45. 45. Platelets45Bone MarrowLimited By Source Infinite SupplyCord Blood hESC
  46. 46. Representative iPS-platelet prep46Blood platelets iPS plateletsCD42bCD41a
  47. 47. Achieving Function and Scale47• Ultrastructural and morphological features of SC-derived platelets areindistinguishable from normal blood platelets.• SC-derived platelets respond to thrombin stimulation, formmicroaggregates, and facilitate clot formation and retraction.• SC-platelets form lamellipodia and filopodia in response to thrombinactivation, and tethered to each other as observed in normal blood.• SC-derived platelets contribute to developing thrombi at sites of laser-inducedvascular injury in mice - first evidence for in vivo functionality of SC-derived platelets.
  48. 48. Activation48iPS-PLT’s display appropriatecytoskeletal functionin glass spreading assays.
  49. 49. Characterization of Platelets49hESC- and iPS-derived platelets participatein clot formation and retraction
  50. 50. Clinical Program Status50• Animal model studies showproper in vivo function• Achieved clinical dosescale manufacturing• Completely feeder-free process(bioreactor capable!)• Pre-IND meeting requestedwith FDAHuman platelets incorporating intolaser-induced into mouse thrombus
  51. 51. ACT Corporate Overview
  52. 52. Financial Update – Strong Balance Sheet52• Company ended 2012 Q3 with $42 million in cash oravailability of cash through financing commitments• $16 million annual cash-burn rate(funded through early 2015)• Settled nearly all litigation hangover from previousmanagement
  53. 53. ACT Management TeamHighly Experienced and Tightly Integrated Management TeamGary Rabin – Chairman & CEODr. Robert Lanza, M.D. – Chief Scientific OfficerEdmund Mickunas – Vice President of Regulatory AffairsDr. 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 ManufacturingKathy Singh - ControllerRita Parker – Director of OperationsDr. Matthew Vincent, Ph.D. – Director of Business DevelopmentBill Douglass – Dir. of Corporate Communications & Social Media53
  54. 54. Dr. Ronald M. Green: ChairmanDr. Judith BernsteinDr. Jeremy B.A. GreenDr. Robert KauffmanDr. Carol A. TauerACT LeadershipGary Rabin: Chairman & CEODr. Robert S. Langer, ScD: Prolific medical inventor; Chair – ACT SABGregory S. Perry: EVP – ImmunogenMichael Heffernan: CEO – Collegium PharmaZohar Loshitzer: CEO Presbia; Founder LifeAlert MedicalDr. Alan C. Shapiro: Renowned business school professor54World Class Board of DirectorsHighly-regarded Ethics Advisory Board
  55. 55. Thank youFor more information, visit www.advancedcell.com
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