Novel Strategies for the Scalable Manufacture of Cellular Therapeutics from Pluripotent Stem Cells: Commercial Implications GTCbio 4th Stem CellProduct Development &Commercialization  April 29 2015 

 Safe Harbor Statement  2  The matters discussed in this presentation include forward looking statements which are subject to various risks, uncertainties, and other factors that could cause actual results to differ materially from the results anticipated. Such risks and uncertainties include but are not limited to the success of BioTime in developing new stem cell products and technologies; results of clinical trials of BioTime products; the ability of BioTime and its licensees to obtain additional FDA and foreign regulatory approval to market BioTime products; competition from products manufactured and sold or being developed by other companies; the price of and demand for BioTime products; and the ability of BioTime to raise the capital needed to finance its current and planned operations. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. As actual results may differ materially from the results anticipated in these forward-looking statements they should be evaluated together with the many uncertainties that affect the business of BioTime and its subsidiaries, particularly those mentioned in the cautionary statements found in BioTime's Securities and Exchange Commission filings. BioTime disclaims any intent or obligation to update these forward-looking statements. 

 The Opportunity in Pluripotency  3        Scalable source of all human cell typesImmortal substrate allowing complex genetic modifications 

 Manufacturing Technology 1.0  ES Cells  Purification ofdesired cell type  Problem of impurities  Differentiation  Traditional Manufacture  The Challenge 

 OPC1: Previous Phase 1 Trial  5  Feasible and Safe            Five subjects received 2 mil OPC1 cells, followed for >4 years Clean safety profile observed to date:No serious adverse events related to surgery, OPC1, or immunosuppressionNo unexpected neurological changesNo adverse changes on MRIMonitoring through one year shows no evidence of immune responses to OPC1Potential evidence of biological activity:MRI results in 4 of 5 subjects are consistent with prevention of lesion cavity formation 

 6  OPC1  Current Phase 1/2a Trial     

 Telomerase Cancer Vaccine  7  Potential Vaccine for ≈ 95% Cancer Types              Phase 1 Prostate CancerDukeJ. Immunol 2005, 174:3798  Phase 2Acute Myelogenous Leukemia Multi CenterKhoury ASH 2010  # Treated Patients  20  21  Tolerability  Excellent  Excellent  Patients Immunized Against hTERT  95%  55%  Laboratory & Clinical Impact  Highly Significant Increase in PSA Doubling Times Clearance of Circulating Immune Complexes  Significant Increase in 12 Month DFS in High Risk Group (N=11) Compared to Published Historical Controls  VAC1 is Safe and Stimulates a-Telomerase Immune Responses in 2 Clinical Trials Biomarkers Improved or Stabilized 

 Telomerase Cancer Vaccine  8  The VAC2 Platform         

 

 9  1 Source: Cancer Research Technologies, 2 Source: National Institutes of Health. 3 Source: Decision Resources  VAC2  Trial Design     

     Age-Related Macular Degeneration (AMD)      OpRegen  Photoreceptor function and angiogenesisinhibition depend on RPE cellsLoss of RPE cells can cause either thedry or wet forms of AMD           Retinal PigmentEpithelium (RPE)  Choroid  Photoreceptors  Drusen  10 

   Clinical Trial Design      OpRegen  11  Phase I/IIa dose escalation safety and efficacy study of OpRegen transplanted subretinally in patients with advanced dry-form of AMD (Geographic Atrophy)Open label, non-randomized, sequential, single center trialStudy Site: Hadassah University Medical Center, Jerusalem, IsraelDose and Administration: Single injection of 50,000-500,000 cells in saline delivered into the subretinal space. Part 1Cohort 1: 3 Patients, BCVA 20/200 or less, 50,000 cellsCohort 2: 3 Patients, BCVA 20/200 or less, 200,000 cellsCohort 3: 3 Patients, BCVA 20/200 or less, 500,000 cellsPart 2Cohort 4: 6 Patients, BCVA 20/100, 500,000 cells 

 Manufacturing Technology 1.0  12  In addition to the challenge of the >1000-fold complexity of cell types coming from ES cells, and the challenge of manufacturing pure and identified product, the highly complex fate decisions lead to a challenge of lot-to-lot variability.  Embryoid Body  Activin A  FGF2  TGFb3  Desired Cell Type  The Challenge 

 Challenges of Pluripotency  13    ScalabilityReproducibilityPurityIdentity 

 Manufacturing Technology 2.0  14  ES Cells  Purification ofdesired cell type  Problem of impurities  Differentiation  >200-fold diversityScalable, monoclonallypurified progenitors  BioTime’s proprietary PureStem manufacturing technology yields >200 highly purified, identified, and scalable human cell types  Traditional Manufacture  PureStem Technology  ES Cells 

 15  Manufacturing Technology 2.0 

 16  Manufacturing Technology 2.0 

 17  Manufacturing Technology 2.0  >200 Cell Types Clonally Expandable 

   HyStem – A Critical Combination  18              Polymerizes safely in vivo   Stays as liquid for ~ 20 minutes  Supports cells including adipocytes in 3-D            Cast Hydrogel  Cells in Sponge                                    Injectable  Multiple Formulations                    Durable Films  3-D Lattices  Heparin-mediated Slow Release   

 Fate Space Screening  19  Chondrogenesis    Angiogenesis    Osteogenesis    Neurogenesis    Myogenesis              TGFbs  FGFs  BMPs  RA  WNTs  >100 Scalable Clonal hEP Lines   Array of Diverse Differentiation Conditions   Approx 4,000Gene Expression Microarrays 

 Fate Space Screening  20  T42 in MM Culture  T42 in HyStem Culture 

 Purified Endothelium  Purity  Monoclonal Endothelium  GFP Endothelium (168 hrs)  Monoclonal  Heterogeneous 

 22  Precise Identity  Foxf1 Genes & Dev. 18: 937-951Lhx8 Science 24:306: 2255-2257Barx1 Development 136: 637-645   Lhx8  Foxf1  Barx1 

 Scalability 

 Osteochondral Differentiation  24  NHAC    MSCs    4D20.8    SM30    E15    MEL2    7SMOO32    7PEND24    SK11    COL2A1 qPCR  Micromass with TGFb3 Condition 

 Osteochondral Differentiation  25  PureStem progenitor lines targeting orthopedics      OTX-CP03  Experimentally-induced trauma  4 weeks   

 Reproducibility  26 

 Limb Bud Markers  27    Distal LPM displays unique molecular markers  Taher L, Collette NM, Murugesh D, Maxwell E, Ovcharenko I, et al. (2011) Global Gene Expression Analysis of Murine Limb Development. PLoS ONE 6(12): e28358. doi:10.1371/journal.pone.0028358   MandibularMesenchyme  Forelimb  Hindlimb 

 Limb Bud Markers  28    B16  E44  RAD20.5  MSCs  Xgene  NHAC  RASMO19  RAPEND18  C4ELSR10  SK11  SM30     

 29  Precise Neural Crest Cell Types  E69  T42 

 30  Precise Neural Crest Cell Types  Choroid PlexusOf 4th Ventricle  MeningesOf Upper Medulla  Basio-Occipital Bone  CYP26B1  TTR  In situ images from Genepaint.org 

 Diversity of Adipocyte Progenitors  31        Adipogenesis in Renevia 

 HyStem Trial - Renevia™   32  Renevia™ is an injectable matrix designed to safely produce 3-D tissue in vivo, keeping cells where the surgeon places them. It is expected to have numerous applications in multiple tissue typesPivotal trial for CE mark for use in HIV-associated lipoatrophy in combination with autologous lipotransfer now underwayEstimated 3.5M people worldwide have HIV-related lipoatrophy In addition, a greater number of people have lipoatrophy due to trauma or agingMany other potential applications in combination with adult and ESC therapies  Age-Related Lipoatrophy 

 33    ReneviaTM Pivotal Trial  Multicenter, randomized, controlled, single blind trial     Treated vs. delayed treatment control  25 - 92 subjects in each group with treatment effect measured at 1, 3, and 6 months  Primary Endpoint   Increase in skin thickness as measured by ultrasound at 6 months  Secondary Endpoint  Mid-face volume deficit score Global aesthetic improvement score  Sites  2 sites in Palma de Mallorca, Spain  Trial Design 

 Diversity of Adipocyte Progenitors  34    N Engl J Med 2009 360;19  

 Brown Adipocyte Progenitors 

       Advantages of HyStem & Clonal EPs  36    Rare and potentially valuable cell typesScalable & reproducible productPurity and identity of cellsA formulation optimizing viability & immobilization of engraftment