Lineage Cell Therapeutics, Inc. · AMEX:LCTX
Lineage Cell Therapeutics — Biotime — GTCbio 4th Stem Cell Product Development & Commercialization 2015
36 slides from Lineage Cell Therapeutics's conference presentation, Apr 29, 2015
Slide 1: Novel Strategies for the Scalable Manufacture of Cellular Therapeutics from Pluripotent Stem Cells
Novel Strategies for the Scalable Manufacture of Cellular Therapeutics from Pluripotent Stem Cells: Commercial Implications GTCbio 4th Stem CellProduct Development &Commercialization April 29 2015
Slide 2: Safe Harbor Statement
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 n
Slide 3: The Opportunity in Pluripotency
The Opportunity in Pluripotency 3 Scalable source of all human cell typesImmortal substrate allowing complex genetic modifications
Slide 4: Manufacturing Technology 1.0
Manufacturing Technology 1.0 ES Cells Purification ofdesired cell type Problem of impurities Differentiation Traditional Manufacture The Challenge
Slide 5: OPC1: Previous Phase Trial Feasible and Safe
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
Slide 6: OPC1 Current Phase 1/2a Trial
6 OPC1 Current Phase 1/2a Trial
Slide 7: Telomerase Cancer Vaccine
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 & Clin
Slide 8: Telomerase Cancer Vaccine The VAC2 Platform
Telomerase Cancer Vaccine 8 The VAC2 Platform
Slide 9: VAC2 Trial Design
9 1 Source: Cancer Research Technologies, 2 Source: National Institutes of Health. 3 Source: Decision Resources VAC2 Trial Design
Slide 10: Age-Related Macular Degeneration (AMD) OpRegen
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
Slide 11: Clinical Trial Design OpRegen
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, Jerusal
Slide 12: Manufacturing Technology 1.0
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
Slide 13: Challenges of Pluripotency
Challenges of Pluripotency 13 ScalabilityReproducibilityPurityIdentity
Slide 14: Manufacturing Technology 2.0
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
Slide 15: Manufacturing Technology 2.0
15 Manufacturing Technology 2.0
Slide 16: Manufacturing Technology 2.0
16 Manufacturing Technology 2.0
Slide 17: Manufacturing Technology 2.0 >200 Cell Types Clonally Expandable
17 Manufacturing Technology 2.0 >200 Cell Types Clonally Expandable
Slide 18: HyStem – A Critical Combination
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
Slide 19: Fate Space Screening
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
Slide 20: Fate Space Screening
Fate Space Screening 20 T42 in MM Culture T42 in HyStem Culture
Slide 21: Purified Endothelium
Purified Endothelium Purity Monoclonal Endothelium GFP Endothelium (168 hrs) Monoclonal Heterogeneous
Slide 22: Precise Identity
22 Precise Identity Foxf1 Genes & Dev. 18: 937-951Lhx8 Science 24:306: 2255-2257Barx1 Development 136: 637-645 Lhx8 Foxf1 Barx1
Slide 23: Scalability
Scalability BIOTIME Estimated Cell Number If Scaled Cells Presently in Inventory to Passage 30 CELL LINE 4020.8 Cell Numbe: Example ns 100 300 900 2700 8100 24300 72900 218700 656100 1968300 5904900 17714700 53144100 159432300 478296900 1434890700 4304672100 12914016300 38742048900 1.16226E+11 3.486
Slide 24: Osteochondral Differentiation
Osteochondral Differentiation 24 NHAC MSCs 4D20.8 SM30 E15 MEL2 7SMOO32 7PEND24 SK11 COL2A1 qPCR Micromass with TGFb3 Condition
Slide 25: Osteochondral Differentiation
Osteochondral Differentiation 25 PureStem progenitor lines targeting orthopedics OTX-CP03 Experimentally-induced trauma 4 weeks
Slide 26: Reproducibility
Reproducibility BIOTIME COL2A1 “o 30 15000 20 20 10000 20 150 000 10 “ATL oo. . oo RFUs RFUs ° - ots rere Soo F SPF Sor Se oe SEE SESE 2 SESE SESE Ss soe sees eye FSI ghIaI” _ahaeadse™ COOP ae I Eee FSS SF SLE < oo Sooo" eek Ma oS Se Z et SEE SERS ES. se OE EEF EF SEE EEF Ge og! SPP _ ge LISS SSS PI
Slide 27: Limb Bud Markers
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
Slide 28: Limb Bud Markers
Limb Bud Markers 28 B16 E44 RAD20.5 MSCs Xgene NHAC RASMO19 RAPEND18 C4ELSR10 SK11 SM30
Slide 29: Precise Neural Crest Cell Types
29 Precise Neural Crest Cell Types E69 T42
Slide 30: Precise Neural Crest Cell Types
30 Precise Neural Crest Cell Types Choroid PlexusOf 4th Ventricle MeningesOf Upper Medulla Basio-Occipital Bone CYP26B1 TTR In situ images from Genepaint.org
Slide 31: Diversity of Adipocyte Progenitors Adipogenesis in Renevia
Diversity of Adipocyte Progenitors 31 Adipogenesis in Renevia
Slide 32: HyStem Trial - 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
Slide 33: Renevia Pivotal Trial
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 End
Slide 34: Diversity of Adipocyte Progenitors
Diversity of Adipocyte Progenitors 34 N Engl J Med 2009 360;19
Slide 35: Brown Adipocyte Progenitors
Brown Adipocyte Progenitors
Slide 36: Advantages of HyStem & Clonal EPs
Advantages of HyStem & Clonal EPs 36 Rare and potentially valuable cell typesScalable & reproducible productPurity and identity of cellsA formulation optimizing viability & immobilization of engraftment
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