Brainstorm Cell Therapeutics Inc. · OTC:BCLI

Brainstorm Cell Therapeutics — ALS ONE, Industry Presentations (October 2022)

15 slides from Brainstorm Cell Therapeutics's conference presentation, Oct 7, 2022

  1. Slide 1: The Relationship between CSF Biomarkers and Efficacy of Treatment with NurOwn (MSC-NTF cells)

    The Relationship between CSF Biomarkers and Efficacy of Treatment with NurOwn (MSC-NTF cells) ALS ONE, Industry Presentations Stacy R. Lindborg, Ph.D. Chief Development Officer, Brainstorm Cell Therapeutics October 7, 2022

  2. Slide 2: NurOwn Phase 3 featured participants with advanced ALS disease

    Participants with NurOwn Phase 3 featured participants with advanced ALS disease baseline ALSFRS-R  25 are impacted by the resulting in a floor effect floor of the scale ALSFRS-R % participants Subscale with value of 0 at baseline Bulbar 7% Fine Motor 42% Gross Motor 37% Respiratory 1%  Number of

  3. Slide 3: NurOwn treatment suggests effect in participants with less advanced disease

    NurOwn treatment suggests effect in participants with less advanced disease Evidence from trial aligns with historical data when the ALSFRS-R floor effect is accounted for Primary Endpoint: % Response at week 28 Secondary Endpoint: Average Change from 40 baseline to Week 28, ALSFRS-R 35 32.6% 34.6%

  4. Slide 4: Objective

    OBJECTIVE Evaluating the effect of NurOwn and placebo on CSF biomarkers across pathways of neuroinflammation, neurodegeneration and neuroprotection from a Phase 3 RCT • using statistical methods that focus on univariate and multivariate data • to understand the role that baseline ALSFRS-R values pla

  5. Slide 5: Phase 3 Trial Study Design: Designed to exclude slow progressors

    Phase 3 Trial Study Design: Designed to exclude slow progressors Double-blind, Placebo-controlled, Randomized Trial Bone Marrow Aspiration NurOwn Treated (N=95) Designed to exclude slow progressors. R • CSF 0, 2, 4, 8, 12, 16, and 20 weeks 1:1 Inclusion criteria specified: • ALSFRS-R designed to be

  6. Slide 6: Biomarker Analysis Methods

    Biomarker Analysis Methods • 7 CSF samples over 20 weeks - collected prior to and after each treatment • Validated assays at Thermo Fisher, Quanterix, Olink, Ray Biotech and Norgen • Biomarker Statistical Analysis Plan submitted to FDA before trial unblinding • Due to skewness in the distribution, b

  7. Slide 7: Clinical Outcomes Considered as Measure of Efficacy

    Clinical Outcomes Considered as Measure of Efficacy Two different clinical measures based on ALSFRS-R specified in the biomarker SAP: Clinical outcome based on change between pre-treatment and post-treatment: Clinical Response (primary endpoint)a See Cudkowicz, et al. Musc Nerve, Jan 2022 for result

  8. Slide 8: Pre-specified biomarkers passed validation and were analyzed by pathway

    Pre-specified biomarkers passed validation and were analyzed by pathway 16 Neuroinflammatory/Anti-inflammatory markers: Inflammation: CHI3L1/YKL-40, Chitotriosidase-1, ICAM-1, IP-10, MCP-1, OPG, S100B, SDF-1a, TREM-2, GFAP Anti-inflammation: Fetuin-A, IL-37, LAP/TGFβ1, MSR1, miR 146a, miR 146b 8 Neu

  9. Slide 9: ALS Phase 3: Biomarker Evaluation

    ALS Phase 3: Biomarker Evaluation NurOwn decreases Neuroinflammation and Neurodegeneration, and increases Neuroprotection over 20 weeks (BCT-002) Patterns observed with individual biomarkers confirmed in analysis across biomarkers leveraging Principal Component Analysis Neuroinflammation decreased w

  10. Slide 10: NurOwn Improves Biomarkers Across Multiple Pathways Over Time

    NurOwn Improves Biomarkers Across Multiple Pathways Over Time, LS Mean (95%CI) MCP-1 (Pro-Inflammatory) NfL (Neurodegenerative) Biomarker = NfL Biomarker = MCP-1 8.8 Effects (p-values) Effects (p-values) Treatment 0.2994 6.4 Treatment <.0001 Week 0.0104 Week <.0001 Treatment*Week 0.1215 Treatment*We

  11. Slide 11: Biomarkers are not impacted by the floor effect of the ALSFRS-R

    Biomarkers are not impacted by the floor effect of the ALSFRS-R MCP-1 LAP Biomarker = MCP-1 Biomarker = MCP-1 Biomarker = LAP Biomarker = LAP Baseline ALSFRS-R ≤ 25 Baseline ALSFRS Score = [<= 25] Baseline ALSFRS-R > 25 Baseline ALSFRS Score = [> 25] Baseline ALSFRS-R Baseline ALSFRS Score =≤[<=25 2

  12. Slide 12: Biomarkers are not impacted by the floor effect of the ALSFRS-R

    Biomarkers are not impacted by the floor effect of the ALSFRS-R NfL VEGF-A Baseline ALSFRS-R  25 Biomarker = NFL Baseline ALSFRS-R > 25 Biomarker = NFL Baseline ALSFRS-R  25 Biomarker = VEGF-A Baseline ALSFRS Score = [<= 25] Baseline ALSFRS-R > 25 Biomarker = VEGF-A Baseline ALSFRS Score = [> 25]

  13. Slide 13: The Relationship Between Biomarkers and Clinical Outcomes

    The Relationship Between Biomarkers and Clinical Outcomes reveal biomarkers across 3 pathways are important to predicting the clinical response observed Clinical outcome based on a post treatment change (rate of decline): piecewise slope Stepwise Regression Model for • Statistical model identifies 3

  14. Slide 14: Summary

    Summary Changes in biomarkers following NurOwn treatment are statistically linked to clinical outcomes from the trial • Treatment with NurOwn elevates markers of neuroprotection, and lowers markers of neuroinflammation and neurodegeneration over time compared to placebo • The same biomarker response

  15. Slide 15: Manufacturing Sites, Treatment Centers, Funding

    Manufacturing Sites City of Hope Center for Biomedicine & Dana-Farber Harvard Cancer Center Genetics Cell Manipulation Core Treatment Centers Funding 15

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