Human Embryonic and Induced Pluripotent Stem Cells: Biotechnology Entering a New Era of Complexity

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1 Human Embryonic and Induced Pluripotent Stem Cells: Biotechnology Entering a New Era of Complexity GTC 5th Advances in Stem Cell Discovery & Development Conference October 20, 2011

2 Forward Looking Statements 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. Other risk factors are discussed in BioTime s Securities and Exchange Commission filings.

3 Human Pluripotent Stem Cells Pluripotent Stem Cells GMP Master Cell Bank Purity Identity Histocompatibility

4 GMP Master Cell Bank First publication describing the derivation of clinical-grade GMP hes cell lines Comprehensive, multiple stage donor consent FDA approved, GMP human fibroblast feeder cell line Six karyotypically normal hes cell lines successfully derived Four hes cell lines screened for panel of adventitious agents Characterized for pluripotency

5 CIRM Collaboration

6 GMP hes Master Cell Bank Complete Genomic Sequence Cell Line Sequenced Status NIH Approval ESI-014 Pending Pending Approved ESI-017 Completed Normal Approved ESI-035 Completed Normal Approved ESI-049 Completed Normal Approved ESI-051 Completed Normal Approved ESI-053 Completed Normal Approved

7 Purity: Manufacturing Technology 1.0 ES Cells Step 1: Differentiation Step 2: Purification of desired cell type Toxicity: Ectopic Cysts Tumors

8 Manufacturing Technology 2.0 >200 Cell types isolated Embryonic Stem Cells

9 Human Embryonic Stem Cells

10 Human Embryonic Stem Cells

11 Manufacturing Technology 2.0 Large diversity of cell types

12 Manufacturing Technology 2.0

13 Manufacturing Technology 2.0 Large diversity of cell types Clonal derivation as a purification modality

14 Manufacturing Technology 2.0 Large diversity of cell types Clonal derivation as a purification modality Directly scalable, cryopreservable

15 Manufacturing Technology 2.0 >200 Cell types isolated Diversity Precise identity Purity Scalability Patents pending

16 Manufacturing Technology 2.0 Large diversity of cell types Clonal derivation as a purification modality Directly scalable, cryopreservable Robust culture enables functional assays, and use of cell library in drug discovery

17 hep Fate Space Screen TGFbs Chondrogenesis FGFs Angiogenesis BMPs Osteogenesis RA Neurogenesis WNTs Myogenesis >100 Scalable Clonal hep Lines Array of >500 Differentiation Conditions Gene Expression

18 Definitive Cartilage Progenitors 7SMOO32 COL2A1 qpcr 4D20.8 MSCs 7PEND24 E15 MEL2 SM30 SK11 NHAC

19 hep Fate Space Screen MEL2 4D20.8 E15 7SMOO32 SK11 SM30

20 hep Fate Space Screen

21 hep Fate Space Screen LHX8 Neural Crest Line 4D20.8 LHX8 in situ Gray PA, Science 2004 Dec 24;306(5705)

22 hep Fate Space Screen MSCs 4D20.8 NHAC DPSCs SM30 E15 MEL2

23 hep Fate Space Screen MSCs MEL2 Z11

24 hep Fate Space Screen

25 hep Fate Space Screen * * *

26 OTX-CP07 Stability P33 OTX-CP07 MSCs P12 P12 P33 P8

27 HyStem Rx A Universal Cell Delivery Device Cells in Provisional HyStem-Rx Matrix Cells in Remodeled Tissue Matrix

28 Joint Repair Composite with HyStem Experimentally-induced trauma Implant OTX-CP03 OTX-CP07 4 weeks

29 HyStem Rx A Universal Cell Delivery Device Stays as liquid for ~ 20 minutes Injectable gel Cast hydrogel Tissue Cells in Sponge Sponge

30 HyStem Rx Neuro Tox No difference in reactive astrocytes No difference in macrophages/microglia No difference in neuronal number or blood vessel structure

31 RASMO12 Clonal EP Cells Distal HOX A4,B8,C8 WT1 NPNT TSHZ2

32 RASMO12 Clonal EP Cells RASMO12

33 U31 Clonal EP Cells HOX- NTRK+ TH+ DARPP32+ CRABP1+ Inducible PNMT

34 Progenitor U31 U31 MM PPP1R1B: Aka DARPP32: is a downstream target of the dopamine receptor.

35 Progenitor U31 U31 MM specifically expresses GAT1 (SLC6A1) Homo sapiens solute carrier family 6 (neurotransmitter transporter, GABA), member 1 (SLC6A1) U31 MM NSCs

36 Progenitor U31 SLC6A1 SLC6A1

37 OpRegen TM Teva Option Idelson et al, Cell Stem Cell 2009

38 Stable Vascular Progenitors Monoclonal Endothelium Heterogeneous Monoclonal GFP Endothelium (168 hrs)

39 Advantages of Monoclonal Progenitors Improved purity and identity. Direct scalability and stability. Facilitates manufacture of therapeutics. Enables fate space screening and bioinformatics.

40 NYSE Amex: BTX