Brainstorm Cell Therapeutics Inc. · OTC:BCLI
Brainstorm Cell Therapeutics — 13th Annual California ALS Research Summit 2023
18 slides from Brainstorm Cell Therapeutics's conference presentation, Jan 20, 2023
Slide 1: The Debamestrocel (NurOwn) Treatment Effect in Phase 3 as accessed by ALSFRS-R and CSF Biomarkers
The Debamestrocel (NurOwn) Treatment Effect in Phase 3 as accessed by ALSFRS-R and CSF Biomarkers 13TH ANNUAL CALIFORNIA ALS RESEARCH SUMMIT Stacy R. Lindborg, Ph.D. Brainstorm Cell Therapeutics January 20, 2023
Slide 2: 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
Slide 3: NurOwn Phase 3 Featured Participants with Advanced ALS Disease Resulting in Floor Effect
NurOwn Phase 3 Featured Participants with Advanced ALS Disease Resulting in Floor Effect Per FDA: “[a] floor effect can occur at the item level or at the scale score level. The floor effect occurs when the scale of measurement is not able to capture progression at the bottom of the scale.” FDA, Pati
Slide 4: Participants with Baseline ALSFRS-R ≤ 25 Impacted by ALSFRS-R Floor
Participants with Baseline ALSFRS-R ≤ 25 Impacted by ALSFRS-R Floor ▪ 23% (44/189) of participants with baseline ALSFRS-R ≤ 25 ▪ ALSFRS-R cannot measure further decline once items reach 0 ▪ Impacts ability to differentiate rates of clinical decline between treatment groups ALSFRS-R Subscale % Partic
Slide 5: Inability to Measure Further Decline Results in Misclassification of Response on Primary Endpoint
Inability to Measure Further Decline Results in Misclassification of Response on Primary Endpoint • Participants can achieve response criteria (i.e., ≥ 1.25 points/month reduction in decline compared to pre-treatment period) because of floor effect of scale – Suggesting that participants with worst
Slide 6: NurOwn treatment suggests effect in participants with less advanced disease
NurOwn treatment suggests effect in participants with less advanced disease Primary Endpoint: % Response at week 28 Secondary Endpoint: Average Change from baseline to Week 28, ALSFRS-R 40.00% 0 p = 0.305 † % Response by Treatment, Week 28 p = 0.453 Average change from Baseline 35.00% -1 to Week 28,
Slide 7: ALS Phase 3 Secondary Endpoint by Baseline ALSFRS-R > 25
ALS Phase 3 Secondary Endpoint by Baseline ALSFRS-R > 25: NurOwn participants with less advanced disease had greater preservation of function compared to Placebo ALSFRS-R MMRM Change from Baseline to Week 28 Secondary Endpoint ALSFRS-R n (%) total MSC-NTF LS Placebo LS Delta p-value Baseline partici
Slide 8: Participants with Lower Baseline ALSFRS-R Scores Had Greater Issues with Floor Effect
Participants with Lower Baseline ALSFRS-R Scores Had Greater Issues with Floor Effect; Decreased with Higher Baseline ALSFRS-R Scores Floor Effect at baseline No Floor Effect at baseline 8
Slide 9: Participants Receiving NurOwn with No Evidence of Floor Effect at Baseline Suggests Treatment Effect
Participants Receiving NurOwn with No Evidence of Floor Effect at Baseline Suggests Treatment Effect Secondary Endpoint: Average Change from Primary Endpoint: % Response at week 28 baseline to Week 28, ALSFRS-R % Response by Treatment, week 28 45.00% p = 0.035 0 Average change from Baseline 40.00% p
Slide 10: 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
Slide 11: Pre-specified biomarkers passed validation and were analyzed
Pre-specified biomarkers passed validation and were analyzed 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 Neurodegenerat
Slide 12: Treatment with NurOwn significantly elevates markers of neuroprotection, and lowers neuroinflammation and neurodegeneration
Treatment with NurOwn significantly elevates markers of neuroprotection, and lowers markers of neuroinflammation and neurodegeneration compared to placebo Number of Biomarkers with overall significant treatment effect or Primary Biomarker Pathway Biomarkers treatment by time effect n (%)‡ All partic
Slide 13: NurOwn Improves Biomarkers Across Multiple Pathways Over Time, LS Mean (95%CI)
NurOwn Improves Biomarkers Across Multiple Pathways Over Time, LS Mean (95%CI) *p < 0.05, based on change from baseline
Slide 14: Biomarker data reveal NurOwn biologically active in all trial participants
Biomarker data reveal NurOwn biologically active in all trial participants, not impacted by floor observed with ALSFRS-R • Neuroprotection: Rapid increase with NurOwn in both subgroups relative to placebo, strong treatment effect • The trend of NurOwn compared to Placebo is generally consistent acro
Slide 15: Biomarker data reveal NurOwn biologically active in all trial participants
Biomarker data reveal NurOwn biologically active in all trial participants, not impacted by floor observed with ALSFRS-R • Neuroinflammatory Biomarkers: A large reduction in inflammation at Week 2, indicating a treatment effect • Neurodegeneration: NfL values decreased for NurOwn participants while
Slide 16: Relationship Between Biomarkers and Clinical Outcomes reveal biomarkers across 3 pathways
Relationship Between Biomarkers and Clinical Outcomes reveal biomarkers across 3 pathways important to clinical response observed Clinical outcome based on a post treatment change (rate of decline): piecewise slope Stepwise Regression Model for NurOwn Group p-value • Statistical model identifies 3 b
Slide 17: Summary
Summary ▪ NurOwn marginally better outcomes for primary and key secondary endpoints ➢ Non-significant improvement due to confounding floor effect ▪ NurOwn significantly better outcomes in analyses controlling for floor effect ➢ Outcomes align with historical data and power calculations ➢ Significanc
Slide 18: 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 18
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