Brainstorm Cell Therapeutics Inc. · OTC:BCLI

Brainstorm Cell Therapeutics — ALS Research Forum January 24, 2019

21 slides from Brainstorm Cell Therapeutics's conference presentation, Jan 24, 2019

  1. Slide 1: ALS Research Forum January 24, 2019

    ALS Research Forum January 24, 2019 NurOwn Phase 3 Clinical Trial Update Ralph Kern MD MHSc Chief Operating Officer and Chief Medical Officer Brainstorm Cell Therapeutics 1

  2. Slide 2: NurOwn® ALS Clinical Development

    NurOwn® ALS Clinical Development 4Q 2020 ALS US Phase 3 Topline Data Readout 2017 2019 ALS ALS US Phase 3 US Phase 3 2014 Randomized trial Fully Enrolled ALS US Phase 2 2010 Randomized trial 2007 ALS Phase 1/2a NurOwn Open label Preclinical Development 200 26 48 # of Study Participants Phase 1/2 Pha

  3. Slide 3: NurOwn® (MSC-NTF Cells) Technology Platform

    NurOwn® (MSC-NTF Cells) Technology Platform MSC Cell Identity (Surface Markers) CD44 CD73 CD90 CD105 MSC MSC-NTF CD3 Neuroprotection CD14 CD19 Immunomodulation CD34 CD45 HLA-DR (Fold Increase NTFs Co-culture MSC-NTF MSC-NTF vs. MSC) and PBMCs (% Reduction) MSC LIF 100 HGF MSC-NTF GDNF 50 BDNF VEGF 0

  4. Slide 4: CSF cell and molecular delivery system: 2 step process

    CSF cell and molecular delivery system: 2 step process 2 1 (1) CSF enters the periarterial spaces driven by arterial pulsation (2) CSF moves from the periarterial compartment into the ISF space facilitated by aquaporin 4 (AQP4) water channels on astroglia end-feet, a process enabling CSF-ISF mixing

  5. Slide 5: CSF cell and molecular delivery system: mechanisms

    CSF cell and molecular delivery system: mechanisms Courtesy of Iben Lundgaard Anesth Analg 2004 5 5 Illif et al Sci Transl Med. 2012

  6. Slide 6: BCT-001-US Phase 2 ALS Study

    BCT-001-US Phase 2 ALS Study ClinicalTrials.gov identifier NCT02017912 Berry et al Neurology 2019 6

  7. Slide 7: Phase 2 ALS Study Design

    Phase 2 ALS Study Design ClinicalTrials.gov identifier NCT02017912 Berry et al Neurology 2019 7

  8. Slide 8: Phase 2 ALS Clinical Trial Demographics: Baseline Characteristics Balanced

    Phase 2 ALS Clinical Trial Demographics: Baseline Characteristics Balanced 8 Berry et al Neurology 2019

  9. Slide 9: ALSFRS-R Efficacy Outcomes

    ALSFRS-R Efficacy Outcomes All n=46 Rapid Progressors n=21 A Change from post-treatment to pre-treatment slope B Change from post-treatment to pre-treatment slope 4 4 ALSFRS-R LS mean change in slope * 3 3 2 2 * 1 Mean ALSFRS-R 1 MSC-NTF Post-pre slope change 0 0 -1 Placebo -1 -2 -2 2wks 4wks 8wks 1

  10. Slide 10: CSF Neurotrophic Factors Increased Post-Treatment

    CSF Neurotrophic Factors Increased Post-Treatment VEGF HGF LIF 1000 600 18 900 ** *** * 500 16 800 14 700 400 12 pg/ml 600 NurOwn® 10 500 300 8 400 (n = 26) 300 200 6 4 200 100 V5 -Pre transplantation 100 2 0 0 0 V5 V6 V5 V6 V5 V6 V6 - Post transplantation 1000 600 18 900 16 500 800 14 700 Placebo 4

  11. Slide 11: CSF Inflammatory Biomarkers Reduced Post-Treatment

    CSF Inflammatory Biomarkers Reduced Post-Treatment MCP-1 SDF-1 50,000 CHIT-1 50 250 *** ** 45,000 45 40,000 * 40 200 35 35,000 NurOwn® 30 150 30,000 pg/ml 25 25,000 (n = 26) 20 100 20,000 15 15,000 10 50 10,000 V5 -Pre transplantation 5 5,000 0 0 0 V6 - Post transplantation V5 V6 V5 V6 V5 V6 50 250

  12. Slide 12: Post-treatment % reduction CSF MCP-1, Caspase-3 and SDF-1

    Post-treatment % reduction CSF MCP-1, Caspase-3 and SDF-1 MCP-1 (40%) Caspase-3 (40%) SDF-1 (22%) MCP-1 Caspase-3 SDF-1 10 40 10 30 0 0 20 % Caspase-3 reduction % MCP-1 reduction % SDF-1 reduction p=0.001 10 -10 -10 p=0.0001 0 p=0.096 -20 -10 -20 -20 -30 -30 -30 -40 -40 -40 -50 -50 -60 -50 MSC-NTF P

  13. Slide 13: MCP-1 expression is increased in the spinal cord and motor cortex of ALS patients

    MCP-1 expression is increased in the spinal cord and motor cortex of ALS patients Spinal Cord Brain Degenerating Betz cells express MCP-1 Betz cells surrounded by CCR2+ invading monocytes 13 Henkel Ann Neurol 2004 Jara et al J Neuroinflamm 2019

  14. Slide 14: CSF MCP-1 is increased in ALS and correlates with function and survival

    CSF MCP-1 is increased in ALS and correlates with function and survival MCP-1 meta-analysis (n=7) MCP-1:ALSFRS-R Correlation MCP-1:Survival Correlation CSF MCP-1 CSF MCP-1 Chen Front Immunol 2018, Tateishi J Neuroimmunology 2010, Gille JNNP 2019 14

  15. Slide 15: Phase 2 ALS Clinical Trial: Biomarker Correlations

    Phase 2 ALS Clinical Trial: Biomarker Correlations MCP-1/VEGF 2.5 Treated Placebo 2 Pre-treatment Post-treatment Pre-treatment MCP-1\VEGF ratio 1.5 CSF MCP-1 inverse 1 correlation with Post-treatment *** VEGF 0.5 0 MSC-NTF- V5 MSC-NTF- V6 Placebo -V5 Placebo -V6 ***T-test p<0.00001 CSF MCP-1 inverse

  16. Slide 16: Strong correlation between CSF MCP-1 (2 weeks) and improvement in disease progression

    Strong correlation between CSF MCP-1 (2 weeks) and improvement in disease progression in treated patients at all time points 4 weeks 8 weeks 12 weeks 6 6 6 4 4 4 p=0.07 p=0.001 Delta ALSFRS-R Slope Delta ALSFRS-R Slope p<0.01 Delta ALSFRS-R Slope 2 2 2 0 0 0 -2 -2 -2 -4 -4 -4 -6 -6 -6 0 10 20 30 40

  17. Slide 17: CSF Chitotriosidase correlates with ALS function and survival and is higher in ALS

    CSF Chitotriosidase correlates with ALS function and survival and is higher in ALS Page 29 of 196 rapid progressors Figure 5 A-C Survival analysis in ALS and abundance of CHIT1, CHI3L1 and CHI3L2 and p-value listed along 17 Aricha et al, MND Boston 2017 Vu L, et al. J Neurol Neurosurg Psychiatry 202

  18. Slide 18: Phase 3 BCT-002-US ALS Clinical Trial Design

    Phase 3 BCT-002-US ALS Clinical Trial Design Pre-treatment period Treatment Period Follow-up period Screening period Weeks -18 -14 -10 -6 -20 -16 -12 -9 -5 0 2 4 8 12 16 20 24 28 Screening RNZ BMA T1 T2 T3 Primary Efficacy Endpoint Visit: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 BMA: Bone Marrow Aspiration

  19. Slide 19: Phase 3 Update

    Phase 3 Update • Enrollment • Phase 3 Study is fully enrolled as of October 2017 • Top line data Q4 2020 • Biomarkers/Genetic testing • Genetic testing for a panel of ALS genetic mutations or gene variants • Testing for T regulatory cells pre- and post-transplant included in a recent protocol amendm

  20. Slide 20: Phase 3 Biomarkers

    Phase 3 Biomarkers Biomarker Type CSF Serum MSC-NTF derived BDNF, GDNF, HGF, LIF, VEGF, BDNF, GDNF, HGF, LIF, VEGF, Neurotropic TSG-6 and a panel of markers TSG-6 and a panel of markers related to neurobiological related to neurobiological Factors and processes, cell death, processes, cell death, Ne

  21. Slide 21: Thank you

    Thank you Massachusetts General Hospital BrainStorm Cell Therapeutics Merit Cudkowicz MD Yossef Levy PhD James Berry MD Yael Gothelf PhD University of Massachusetts Revital Aricha PhD Robert Brown DPhil MD Chaim Lebovits Margaret Owegi MD Haggai Kaspi PhD Mayo Clinic Rochester Minnesota Jonathan Sem

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