Brainstorm Cell Therapeutics Inc. · OTC:BCLI

Brainstorm Cell Therapeutics — Investor Presentation (May 2019)

32 slides from Brainstorm Cell Therapeutics's investor presentation, May 26, 2019

  1. Slide 1: BrainStorm Cell Therapeutics

    ‫בס"ד‬ BrainStorm Cell Therapeutics Prepared NASDAQ: BCLI May 26, 2019 March 22, 2018

  2. Slide 2: Forward Looking Statement

    ‫בס"ד‬ Forward Looking Statement Statements in this announcement other than historical data and information constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implie

  3. Slide 3: Brainstorm at a Glance

    ‫בס"ד‬ Brainstorm at a Glance Clinical stage Advanced Clinical Large Addressable biotechnology Programs Markets Company Autologous cell Amyotrophic Lateral ALS therapies for Sclerosis 30,000 patients neurodegenerative disease Phase 3 (US) Proven Cellular Progressive MS Progressive MS Technology and

  4. Slide 4: Brainstorm’s Cellular Technology Pipeline

    ‫בס"ד‬ Brainstorm’s Cellular Technology Pipeline ALS – Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease) Preclinical Phase 1 Phase 2 Phase 3 Progressive MS – Multiple Sclerosis Preclinical Phase 1 Phase 2 Phase Phase 33 Parkinson’s Disease Preclinical Phase 1 Phase 2 Phase 3 Autism Spectrum Disor

  5. Slide 5: NurOwn® Process

    ‫בס"ד‬ NurOwn® Process 1 2 Isolation Expansion Manufacturing process begins with a Intermediate MSC product is bone marrow aspiration to harvest cryopreserved adult MSCs from the patient Harvesting Cryopreservation Transplantation The proprietary culture medium The cells are injected into the induce

  6. Slide 6: NurOwn® Immunomodulation (in vitro)

    ‫בס"ד‬ NurOwn® Immunomodulation (in vitro) IFN-𝜸 Secretion and T Cell Proliferation Reduced T Regulatory Cells Increased PBMC co-cultured with Activated PBMC co- PBMC only Activated MSC-NTF cultured with MSC-NTF % reduction PBMC (%) cells (%) IFN- 100 6.2 ± 2.24 93.8%  secretion CD4+ T cells 100…

  7. Slide 7: ALS Incidence

    ‫בס"ד‬ ALS Incidence What is ALS? It is estimated that 450,000 people worldwide are living with ALS, with Amyotrophic lateral sclerosis (ALS), also known over 30,000 people in the U.S. suffering from this neurodegenerative as Lou Gehrig’s disease (1), is a progressive condition at any given time. ne

  8. Slide 8: NurOwn® ALS Development

    ‫בס"ד‬ NurOwn® ALS Development Mid 2020 US Phase 3 2017 Topline Data ALS Readout US Phase 3 Randomized 2014 ALS US Phase 2 2010 Randomized 2007 ALS Phase 1/2a NurOwn Open label Preclinical Development 200 26 48 # of Study Participants Phase 1/2 Phase 2 Phase 3

  9. Slide 9: ALS Phase 2 Trial Design and Safety Outcomes

    ‫בס"ד‬ ALS Phase 2 Trial Design and Safety Outcomes Safety Design Study Timeline • 48 participants (16 per site) -12 to -16 weeks Screening (V1) • Randomized 3:1 • Blinded to allocation ~3-4 months 3 month run in period Primary Outcomes -3 to -5 weeks BMA (V4) • No deaths or treatment Transplantatio

  10. Slide 10: Phase 2 Trial – Approach to Data Analysis

    ‫בס"ד‬ Phase 2 Trial – Approach to Data Analysis Phase 2 Trial Efficacy Analysis ALS Rapid Progressor Subgroup Mean change in ✓ Higher correlation of ALSFRS-R ALSFRS-R slope change with survival ALSFRS-R Responder ✓ Higher response rate (~2x) Analysis Rapid progressor ✓ Higher levels of CSF inflamma

  11. Slide 11: ALSFRS-R slope improvement

    ‫בס"ד‬ ALSFRS-R slope improvement (mean pre-post LS mean slope change/month) All participants (n=46) Rapid progressors (n=21) ALSFRS-R LS mean slope change ALSFRS-R LS mean slope change 2 4 1 2 0 0 (2) (1) 2wks (1) 4wks (2) 8wks 12wks 16wks 24wks 2wks 4wks 8wks 12wks 16wks 24wks MSC-NTF Placebo MSC-

  12. Slide 12: Responder Analysis: ≥1.5 points/month ALSFRS-R slope improvement

    ‫בס"ד‬ Responder Analysis: ≥1.5 points/month ALSFRS-R slope improvement at each time point All participants (n=46) Rapid progressors (n=21) % improved % improved 100% 100% 80% 80% 60% 60% 40% 40% 20% 20% 0% 0% 2wks 4wks 8wks 12wks 16wks 24wks 2wks 4wks(1) 8wks 12wks (1) 16wks 24wks MSC-NTF Placebo M

  13. Slide 13: NurOwn Phase 2 ALSFRS-R slope responder analyses

    ‫בס"ד‬ NurOwn Phase 2 ALSFRS-R slope responder analyses 60 50 % responders (≥1.5 points/month improvement) 48 MSC-NTF rapid progressors pre-treatment slope** post-treatment slope 40 ≥ 1.5 points/month 30 improvement ≥ 1.5 points ALSFRS-R* per month improvement 20 24 MSC-NTF All 10 Screening Baseline

  14. Slide 14: NurOwn® Phase 2 ALS Biomarkers: CSF NTFs Significantly Increased

    ‫בס"ד‬ NurOwn® Phase 2 ALS Biomarkers: CSF NTFs Significantly Increased 2 Weeks Post- Treatment Compared to Baseline VEGF (1) HGF (1) LIF (1) Pg/ml Pg/ml Pg/ml 1,000 * 600 ** 18 *** NurOwn® 800 480 15 12 600 360 (n = 26) 9 400 240 6 200 120 3 0 0 0 V5 V6 V5 V6 V5 V6 Pre transplantation Post transpla

  15. Slide 15: NurOwn® Phase 2 ALS Biomarkers: CSF Inflammation Decreased

    ‫בס"ד‬ NurOwn® Phase 2 ALS Biomarkers: CSF Inflammation Significantly Decreased 2 weeks Post-Treatment Compared to Baseline CRP MCP-1 SDF-1 MIP-1b Pg/ml Pg/ml Pg/ml Pg/ml 1,600 50 *** 250 ** 10 NurOwn® 1,280 40 200 8 960 30 150 6 (n = 26) 640 20 100 4 320 10 50 2 0 0 0 0 V5 V6 V5 V6 V5 V6 V5 V6 Pre

  16. Slide 16: NurOwn® Phase 2 ALS Trial Summary

    ‫בס"ד‬ NurOwn® Phase 2 ALS Trial Summary Intrathecal treatment was safe and well tolerated Repeat dosing is needed (2 month dosing interval) Rapid progressor subgroup showed higher efficacy CSF biomarker analyses confirmed mechanism of action

  17. Slide 17: NurOwn® ALS Phase 3 Clinical Trial

    ‫בס"ד‬ NurOwn® ALS Phase 3 Clinical Trial Pre-Treatment Treatment Outcomes • Inclusion criteria • N=200 patients • ALSFRS-R responder analysis ▪ Less than 60 years of age ▪ Enrollment completed by (post-treatment slope change) ▪ SVC > 65% mid-2019 • Safety ▪ ALS ≤ 2 years • 1:1 randomization • ALSFR

  18. Slide 18: AAN May 2019 abstracts

    ‫בס"ד‬ AAN May 2019 abstracts Modulation of CSF Caspase-3 in MSC-NTF Molecular Characterization of VEGF (NurOwn®) in a Phase-2 ALS study: Secretion by MSC-NTF Cells (NurOwn®): correlations with CSF biomarkers and Therapeutic Implications in ALS clinical response Haggai Kaspi, Revital Aricha, Natalie

  19. Slide 19: AAN 2019 Emerging Science Data Blitz

    ‫בס"ד‬ AAN 2019 Emerging Science Data Blitz MODULATION OF CSF CASPASE-3 IN MSC-NTF CELLS (NUROWN®) IN A PHASE 2 ALS STUDY: CORRELATIONS WITH CSF BIOMARKERS AND CLINICAL RESPONSE Revital Aricha1, Haggai Kaspi1, Merit Cudkowicz2, James Berry2, Anthony Windebank3, Nathan Staff3, Margaret Ayo Owegi4, Yo

  20. Slide 20: Phase 2 Study: CSF Biomarkers and Responder Analysis

    ‫בס"ד‬ Phase 2 Study: CSF Biomarkers and Responder Analysis Study Design n=48 (3:1 randomization) ↓MCP-1 ↑miR-132 ↓Caspase 3 -12 to -16 weeks Screening ~3-4 months BMA -3 to -5 weeks IT/IM CSF Week 0 Transplantation Collection Week 2 *** p< 0.001 (V5 and V6) Responder analysis: 100% ALSFRS-R slope i

  21. Slide 21: 2X Greater CSF Caspase-3 % reduction in responders

    ‫בס"ד‬ 2X Greater CSF Caspase-3 % reduction in responders compared to non-responders at 12 weeks post-transplantation* Caspase 3 % reduction post- transplantation 80 p=0.02 60 40 20 0 Responders Non-responders MSC-NTF cells Placebo *** p< 0.001 *Responder defined as ≥100% ALSFRS-R slope improvement

  22. Slide 22: NurOwn® may tip the balance linking neuronal cell death and neuroinflammation

    ‫בס"ד‬ NurOwn® (MSC-NTF cells) may tip the balance linking neuronal cell death and neuroinflammation Neuronal apoptosis activates neuroinflammation via NF𝜅-B MSC-NTF Cell Neuroprotection MSC-NTF Cell Immunomodulation Cell Death and Differentiation 2011

  23. Slide 23: Progressive MS Unmet Need

    ‫בס"ד‬ Progressive MS Unmet Need US MS prevalence Progressive MS 1M 50% Women $4.3B are more likely to be diagnosed with MS than men US annual economic burden Nature Review Disease Primers. November 2018

  24. Slide 24: Progressive MS Rationale

    ‫בס"ד‬ Progressive MS Rationale Chronic/trapped CNS inflammation Impaired Neurotrophic Factor signaling in Progressive MS ▪ Leptomeningeal inflammation1 • MS treatment failure rate correlates ▪ Chronic macrophage/microglia with BDNF methylation status4 activation2 • Reduced expression of BDNF in SPM

  25. Slide 25: MS Preclinical MSC-NTF vs. MSC in EAE Model

    ‫בס"ד‬ MS Preclinical MSC-NTF vs. MSC in EAE Model Intracerebroventricular injection of 2.5X105 cells Barhum et al 2009 J. Mol. Neur.

  26. Slide 26: MS Phase 2 Clinical Trial- Timelines

    ‫בס"ד‬ MS Phase 2 Clinical Trial- Timelines IND granted December 2018 Repeat dosing intrathecal MSC-NTF cells (NurOwn®) 5 leading US MS centers Validated MS clinical outcomes and biomarkers First patient enrolled March 2019, top line data mid 2020

  27. Slide 27: Brainstorm Executive Management Team

    ‫בס"ד‬ Brainstorm Executive Management Team Chaim Lebovits Yael Gothelf PhD. President and CEO VP, Scientific and Regulatory Affairs Uri Yablonka Ralph Kern, MD, MHSc EVP, Chief Business Officer COO and CMO Eyal Rubin Yossef Levy PhD. EVP, CFO VP, Cell Production Arturo Araya Revital Aricha PhD. VP,

  28. Slide 28: Thank You

    ‫בס"ד‬ BrainStorm Cell Therapeutics NASDAQ: BCLI Thank You

  29. Slide 29: Appendix

    pee’ cell therapeutics Appendix

  30. Slide 30: Additional Professional Board Members

    ‫בס"ד‬ Additional Professional Board Members June S. Almenoff MD PhD • Chief Operating Officer & Chief Medical Officer of Innovate Biopharmaceutical • Formerly President and CMO of Furiex Pharmaceuticals and Board member of Tigenix NV (TIG) Tony Polverino PhD • CSO - Kite Pharmaceuticals

  31. Slide 31: Scientific Advisory Board

    ‫בס"ד‬ Scientific Advisory Board Jerold Chun, M.D., PhD -Chair • Neuroscientist, Professor and Senior Vice President of Neuroscience Drug Discovery, Sanford Burnham Prebys Medical Discovery Institute, San Diego CA. Stanley H. Appel, M.D • Peggy and Gary Edwards Distinguished Endowed Chair for the Tr

  32. Slide 32: IP Portfolio

    ‫בס"ד‬ IP Portfolio Allowed Granted Patent Name/ Int. App. No. Pending Jurisdictions Expiry Date Jurisdictions Jurisdictions ISOLATED CELLS AND POPULATIONS COMPRISING SAME FOR THE TREATMENT OF CNS US Europe, US 2030 DISEASES/PCT/IL2006/000699 MESENCHYMAL STEM CELLS FOR THE TREATMENT OF Hong Kong US,

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