Act corporate-presentation jan13


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Act corporate-presentation jan13

  2. 2. This presentation is intended to present a summary of ACT’s (“ACT”, or “Advanced Cell Technology Inc”, or “the Company”) salient business characteristics. The information herein contains “forward-looking statements” as defined under the federal securities laws. Actual results could vary materially. Factors that could cause actual results to 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 from time to time with the Securities and Exchange Commission. The risks identified therein, as well as others not identified by the Company, could cause the Company’s actual results to differ materially from those expressed in any forward-looking statements. Ropes Gray Cautionary Statement Concerning Forward-Looking Statements 2
  3. 3. ACT is a publicly-traded biotechnology company • Develop cellular therapies for the treatment of diseases and conditions that impact hundreds of millions of people worldwide • Premier scientific and research development team • Cell therapies are traditionally derided for being high cost, high touch and 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 worldwide 3 Company Overview
  4. 4. Multiple Pluripotent Cell Platforms Single Blastomere-derived Embryonic Stem Cell Lines Generating hESC lines WITHOUT DESTRUCTION OF EMBRYO Utilizes a SINGLE CELL BIOPSY ACT never needs to make another hESC line again 4 Final Product Definition: hESC-derived products will be manufactured using a cell line made in 2005 from single cell isolated without the destruction of any embryos
  5. 5. Multiple Pluripotent Cell Platforms Induced 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, but Regulatory Agencies (FDA, EMA) proceeding carefully • ACT pursuing platelets as first iPS-derived product (cell fragments – no nucleus, not mitotically active) 5
  6. 6. RPE Clinical Program
  7. 7. 7 Structure of Retina The Retina the light-sensitive tissue lining the inner surface of the eye Retina
  8. 8. 8 Life Support to Photoreceptors Provides nutrients and growth factors • photoreceptors see no blood Recycles Vitamin A • maintains photoreceptor excitability Detoxifies photoreceptor layer Maintains Bruch’s Membrane • natural antiangiogenic barrier • immune privilege of retina Absorbs stray light / protects from UV RPE Layer has multiple critical roles in the health and function of photoreceptors and the retina as a whole.
  9. 9. 9 Life Support to Photoreceptors Loss of RPE cells Build up of toxic waste Loss of photoreceptors Dry AMD Bruch’s Mem. dehiscence Choroidal neovascularization Wet AMD
  10. 10. 10 RPE Therapy- Rationale Dry AMD represents more than 90% of all cases of AMD North America & Europe alone have more than 30 million dry AMD patients who should be eligible for our RPE cell therapy What if we could replace missing RPE cells?
  11. 11. RPE cell therapy may impact over 200 retinal diseases 11 RPE 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. 12 RPE Therapy- Rationale U.S. PATIENT POPULATION EARLY STAGE (10-15M) INTERMEDIATE (5-8M) LATE STAGE (1.75M) ACT’S RPE Cell Therapy should address the full range of dry AMD patients: Halt progression of vision loss in early stage patients Restore some visual acuity in later stage patients
  13. 13. GMP process for differentiation and purification of RPE – Virtually unlimited supply from stem cell source – Optimized for manufacturing Ideal Cell Therapy Product – Centralized Manufacturing – Small Doses – Easily Frozen and Shipped – Simple Handling by Doctor GMP Manufacturing 13 Product Cold Chain is Easily Scaled for Global Sales
  14. 14. Preclinical - Examples 14 control treated Injected human RPE cells repair monolayer structure in eye Photoreceptor layer photoreceptor layer is only 0 to 1 cell thick without treatment
  15. 15. Phase I - Clinical Trial Design 15 SMD and dry AMD Trials approved in U.S., SMD Trial approved in U.K. 12 Patients / trial ascending dosages of 50K, 100K, 150K and 200K cells. Regular Monitoring - including high definition imaging of retina 50K Cells 100K Cells 150K Cells 200K Cells Patient 1 Patients 2/3 DSMB Review DSMB Review
  16. 16. Participating Retinal Surgeons 16 Steven D. Schwartz, MD Chief, Retina Division Ahmanson Professor of Ophthalmology Director, Diabetic Eye Disease and Retinal Vascular Center Director, Ophthalmic Photography Clinical Laboratory Jules Stein Eye Institute Wills Eye Institute Carl D. Regillo, MD Director, Retina Service Professor of Ophthalmology, Jefferson Medical College Byron L. Lam, MD Director, Clinical Visual Physiology Professor of Ophthalmology Bascom Palmer Eye Institute
  17. 17. Participating Retinal Surgeons 17 Dean Eliott, MD Associate Director, Retina Service Professor, Harvard Medical School Massachusetts Eye and Ear Infirmary Moorfields Eye Hospital James Bainbridge, MA MB BChir PhD FRCOphth Professor of Retinal Studies, UCL Institute of Ophthalmology Philip J. Rosenfeld, MD PhD Professor of Ophthalmology Bascom Palmer Eye Institute Edinburgh Royal Infirmary Baljean Dhillon BMed Sci, BM BS, FRCS Surgeon, Edinburgh Royal Infirmary Surgeon, Lothian University Hospitals NHS Trust Professor of Ophthalmology, University of Edinburgh Professor of Visual Impairment Studies, Heriot Watt University
  18. 18. Surgical Overview 18 Procedure: • 25 Gauge Pars Plana Vitrectomy • Posterior Vitreous Separation (PVD Induction) • Subretinal hESC-derived RPE cells injection • Bleb Confirmation • Air Fluid Exchange
  19. 19. Preliminary Results 19 No Adverse Events No signs of hyperproliferation, abnormal growth, rejection or retinal detachment. Persistence of cells Anatomical evidence of hESC-RPE survival and engraftment. Increased pigmentation within the bed of the transplant. Impact on Acuity Recorded functional visual improvements in both patients.
  20. 20. 20 Engraftment and Survival: SD-OCT image collected at month 3 show survival and engraftment of RPE SMD001 3mo post-op Preliminary Results – Structural
  21. 21. 21 Baseline Injection site Month 1 Month 2 SMD PATIENT UK04
  22. 22. 22 Baseline Injection site Month 1 Month 3 SMD PATIENT UK03
  23. 23. 23 Baseline 2 months DRY AMD PATIENT 204
  24. 24. Preliminary Results – Functional 24 Visual Acuity Measurements • SMD Patient: BCVA improved from hand motions to 20/800 and improved 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 Trial 25 12 SMD Patients Treated 3 patients (50K cells cohort) treated – US Trial > Cohort Complete 3 patients (50K cells cohort) treated – UK Trial > Cohort Complete 3 patient (100K cells cohort) treated – US Trial > Cohort Complete 3 patient (100K cells cohort) treated – UK Trial > Cohort Complete No reports of any adverse events or complications due to cells 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 Trial 26 6 dry AMD Patients Treated 3 patients (50K cells cohort) treated > Cohort Complete 3 patient (100K cells cohort) treated > Cohort Complete No reports of any adverse events or complications due to cells per se • No evidence of inflammation or infiltration • No evidence of ectopic tissue formation • No evidence of retinal detachment
  27. 27. RPE Program Milestone Objectives 27 Key upcoming milestones • Continue to treat and review patient data • Define efficacy endpoints and targeted patient visual criteria • Treat earlier stage disease to determine curative power of dissociated cell injections • Simplify shipping and cell-prep to enhance scaled distribution platform
  28. 28. Intellectual Property – RPE Program Treatment Dominant Patent Position for Treating Retinal Degeneration Manufacturing Broad Coverage for Manufacturing RPE Cells from hESC Preparations Claims directed to pharmaceutical preparations of RPE Cells from hESC, including both cell suspensions and scaffolded RPE layers. Sources Issued patents cover RPE Cells derived from other pluripotent 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 Justification 29 Unmet Therapeutic Need Efficacy Patient Prevalence Pharmacoeconomics Patient Advocacy Pricing Justification across all categories of consideration
  30. 30. RPE Program - Investment Thesis 30 • Immense unmet medical need • Small Doses • Immunoprivileged – permits central (allogeneic) source of cells • Noninvasive monitoring of retina Market 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 penetration with 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 protection Hemangioblast cells  Ischemic retinopathy – diabetic retinopathy, vascular occlusions Retinal Neural Progenitor cells Isolated Protective Factors  Photoreceptor Loss, Modulation of Müller Cells  Protection of Retinal Ganglion cells (Glaucoma) Corneal Endothelium, Corneal Epithelium, Descemet’s Membrane  Corneal Disease Mesenchymal Stromal Cells  Glaucoma, Uveitis  Retinitis Pigmentosa  Management of Ocular Surfaces 32 Retina
  33. 33. Mesenchymal Stem Cell Program 33
  34. 34. Mesenchymal Stem Cells in Therapy 34 Mesenchymal stem cells (MSCs) regulate immune responses provide therapeutic potential for treating autoimmune or inflammatory diseases. • Allogeneic - without HLA matching. • Track Record - Adult-derived MSCs already in 200+ clinical trials. Derived from Bone Marrow and Adipost Tissue However, allogeneic adult-derived MSC’s are limited by replicative senescence, and as it turns out, a relative lack of potency
  35. 35. hESC- and iPS – derived MSC 35 ACT Proprietary Process • hESC- and iPS-derived MSCs • virtually inexhaustible source of starting material • replicative capacity is more than 33,000 times greater Advantages for Manufacturing • Use Single Master Cell Bank • Simplifies FDA/regulatory process • No need for continually finding and qualifying donors • Less labor-intensive
  36. 36. Potential applications 36 • >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/irradiated cancer patients • Eye diseases (uveitis, retinal degeneration, glaucoma)
  37. 37. ACT Blood Components Program
  38. 38. Hemangioblast Program: Overview 38 Hemangioblast: common precursor to hematopoietic and endothelial cells. Multipotent cell produces all cell types in the circulatory and vascular systems
  39. 39. Generation of Blood Products 39 Hemangioblasts RBCsHemangioblasts Enucleated RBC’s Process generates large quantities of functional red blood cells and megakaryocytes & platelets
  40. 40. The Case for Platelets 40 Platelets are key elements of hemostasis and thrombosis as well as tissue 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 fields of surgery. . Beyond Donor Supply: Estimate demand for additional 1-2M units/year
  41. 41. The Case for Platelets 41 Donor-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 patients Platelets are the blood product most difficult to maintain without unnecessary wastage. • Platelets do not tolerate refrigeration. • Storage at room temperature is limited to 5–7 days Need for new strategies to generate platelets for infusion therapy.
  42. 42. Platelets 2.0 42 Ability to control platelet manufacturing provides opportunities to improve storage, fine tune platelets for use in wound healing applications, as well as to engineer new roles for platelets beyond traditional 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 Stages 43 Stem Cell Promegakaryoblast megakaryoblast Promegakaryocyte PFC: Proplatelet Formation Cell Platelets Stage I Stage II Stage III Stage IV CFU-GEMM BFU-MK CFU-MK endomitosis
  44. 44. Size and Polyploidy 44 Average size (diameter) of cells at the beginning and 6 days after MK culture DNA ploidy analysis by flow cytometry of CD41a+ cells. DNA ploidy up to 32N was observed in these cells.
  45. 45. Platelets 45 Bone Marrow Limited By Source Infinite Supply Cord Blood hESC
  46. 46. Representative iPS-platelet prep 46 Blood platelets iPS platelets CD42b CD41a
  47. 47. Achieving Function and Scale 47 • Ultrastructural and morphological features of SC-derived platelets are indistinguishable from normal blood platelets. • SC-derived platelets respond to thrombin stimulation, form microaggregates, and facilitate clot formation and retraction. • SC-platelets form lamellipodia and filopodia in response to thrombin activation, and tethered to each other as observed in normal blood. • SC-derived platelets contribute to developing thrombi at sites of laser-induced vascular injury in mice - first evidence for in vivo functionality of SC- derived platelets.
  48. 48. Activation 48 iPS-PLT’s display appropriate cytoskeletal function in glass spreading assays.
  49. 49. Characterization of Platelets 49 hESC- and iPS-derived platelets participate in clot formation and retraction
  50. 50. Clinical Program Status 50 • Animal model studies show proper in vivo function • Achieved clinical dose scale manufacturing • Completely feeder-free process (bioreactor capable!) • Pre-IND meeting requested with FDA Human platelets incorporating into laser-induced into mouse thrombus
  51. 51. ACT Corporate Overview
  52. 52. Financial Update – Strong Balance Sheet 52 • Company ended 2012 Q3 with $42 million in cash or availability of cash through financing commitments • $16 million annual cash-burn rate (funded through early 2015) • Settled nearly all litigation hangover from previous management
  53. 53. ACT Management Team Highly Experienced and Tightly Integrated Management Team Gary Rabin – Chairman & CEO Dr. Robert Lanza, M.D. – Chief Scientific Officer Edmund Mickunas – Vice President of Regulatory Affairs Dr. Irina Klimanskaya, Ph.D. – Director of Stem Cell Biology Dr. Shi-Jiang (John) Lu, Ph.D. – Senior Director of Research Dr. Roger Gay, Ph.D. - Senior Director of Manufacturing Kathy Singh - Controller Rita Parker – Director of Operations Dr. Matthew Vincent, Ph.D. – Director of Business Development Bill Douglass – Dir. of Corporate Communications & Social Media 53
  54. 54. Dr. Ronald M. Green: Chairman Dr. Judith Bernstein Dr. Jeremy B.A. Green Dr. Robert Kauffman Dr. Carol A. Tauer ACT Leadership Gary Rabin: Chairman & CEO Dr. Robert S. Langer, ScD: Prolific medical inventor; Chair – ACT SAB Gregory S. Perry: EVP – Immunogen Michael Heffernan: CEO – Collegium Pharma Zohar Loshitzer: CEO Presbia; Founder LifeAlert Medical Dr. Alan C. Shapiro: Renowned business school professor 54 World Class Board of Directors Highly-regarded Ethics Advisory Board
  55. 55. Thank you For more information, visit