Brainstorm Cell Therapeutics Inc. · OTC:BCLI
Brainstorm Cell Therapeutics — 32nd International Symposia on ALS/MND 2021
19 slides from Brainstorm Cell Therapeutics's conference presentation, December 2021
Slide 1: NurOwn Targets Multiple Disease Pathways in ALS Phase 3 Trial: A Biomarker Analysis
NurOwn Targets Multiple Disease Pathways in ALS Phase 3 Trial: A Biomarker Analysis Brown R, Aricha R, Boulanger B, Windebank A, Goyal N, Miller R, Burford M, Berry J, Katz J, Staff N, Kaspi H, Abramov N, Mehra M, Kern R, Lindborg S, Gothelf Y, Lebovits C, Cudkowicz M 32nd International Symposia on
Slide 2: Disclosures
Disclosures Study funded by Brainstorm Cell Therapeutics Inc Also supported by grants from the California Institute for Regenerate Medicine, the ALS Association and I AM ALS Robert Brown: Consults for APIC Bio and serves on advisory boards of ALSOne, Angel Fund for ALS Research, the Healey Center, A
Slide 3: Phase 3 Trial of NurOwn in ALS Patients: Protocol
Phase 3 Trial of NurOwn® in ALS Patients : Protocol Double-blind, Placebo-controlled, Randomized Trial Treatment Treatment Treatment Inclusion criteria: Bone Marrow • ALSFRS-R ≥ 25 at Screening Aspiration NurOwn Treated (N=95) • Upright SVC ≥ 65% of predicted for gender, height, and age at R CSF sam
Slide 4: Three Pathways Interrogated by Biomarkers
Three Pathways Interrogated by Biomarkers • Neurodegeneration (5) NfL, UCH-L1, pNfH, DR6, Fetuin-A • Neuroprotection (7) Follistatin, VEGF, Clusterin, BDNF, OPG, GDF-15, LIF • Neuroinflammation (9) CHI3L1, Chit-1, IP-10, MCP-1, Trem-2, SDF1a, S100B, MSR1, NMNAT1
Slide 5: Three Approaches to Mapping Biomarkers onto Disease Pathways
Three Approaches to Mapping Biomarkers onto Disease Pathways • Analysis of Individual Biomarkers • Principle component analysis of all biomarkers simultaneously within each pathway • Regression modeling using all biomarkers to predict outcome
Slide 6: Neuroinflammatory Biomarker Concentration in CSF Over Time
Neuroinflammatory Biomarker Concentration in CSF Over Time, LSMean (95%CI) NurOwn significantly lowers pro-inflammatory biomarkers over time compared to placebo MCP-1: Statistically significant reduction with NurOwn SDF-1a: Statistically significant reduction with at each visit, and significant over
Slide 7: Neurodegenerative Biomarker Concentration in CSF Over Time
Neurodegenerative Biomarker Concentration in CSF Over Time, LSMean (95%CI) NurOwn lowers some biomarkers of neurodegeneration over time compared to placebo DR6: Statistically significant reduction with NurOwn, NfL: NurOwn values lowered 82% compared to significant DR6 overall treatment effect Placeb
Slide 8: Neuroprotective Biomarker Concentration in CSF Over Time
Neuroprotective Biomarker Concentration in CSF Over Time, LSMean (95%CI) NurOwn significantly elevates neuroprotective biomarkers over time compared to placebo VEGF: Statistically significant increase with NurOwn at each BDNF: Statistically significant increase with visit, and significant overall tr
Slide 9: Three Approaches to Mapping Biomarkers onto Disease Pathways
Three Approaches to Mapping Biomarkers onto Disease Pathways • Analysis of Individual Biomarkers • Principle component analysis of all biomarkers simultaneously within each pathway • Regression modeling using all biomarkers to predict outcome
Slide 10: Statistical Analysis of Biomarker Data through Principal Components
Statistical Analysis of Biomarker data through Principal Components NurOwn therapy reduces markers of Neuroinflammation and Neurodegeneration, and increases Neuroprotection Trend with individual biomarkers confirmed across biomarkers with PCA • Neuroinflammation decreased with NurOwn treatment over
Slide 11: Three Approaches to Mapping Biomarkers onto Disease Pathways
Three Approaches to Mapping Biomarkers onto Disease Pathways • Analysis of Individual Biomarkers • Principle component analysis of all biomarkers simultaneously within each pathway • Regression modeling using all biomarkers to predict outcome (Stepwise forward regression model – machine learning alg
Slide 12: Final Model Identifies Biomarkers Predictive of Primary Endpoint
Final Model identifies Biomarkers predictive of Primary Endpoint with high accuracy Leveraging model with biomarkers, treatment effect on Primary Endpoint is statistically significant (p=0.003) Stepwise Post baseline • Baseline health was important to predicting logistic model clinical response ENCA
Slide 13: NurOwn Response: Stepwise Linear Regression Model ROC Curve
Confidential – Do not distribute NurOwn response: Stepwise linear regression model to select predictive biomarkers 82.5% accuracy of model predicting clinical response ROC Curve for Selected Model Area Under the Curve = 0.8250 1.00 Receiver Operating Curve Measures accuracy of the model 0.75 Area
Slide 14: Conclusions
Conclusions • NurOwn significantly and consistently elevates markers of neuroprotection, and significantly lowers markers of neuroinflammation and neurodegeneration over time compared to placebo The same conclusion is drawn from individual markers and summaries of markers using PCA • Prespecified
Slide 15: Manufacturing Sites, Treatment Centers and Funding
Manufacturing Sites Confidential- not for external distribution City of Hope Center for Biomedicine & Dana-Farber Harvard Cancer Center Genetics Cell Manipulation Core Treatment Centers Funding 15
Slide 16: Thank You !!
Thank You !!
Slide 17: Extra slides
Extra slides
Slide 18: Biomarkers with Significant Explanatory Value for Clinical Response
Confidential – Do not distribute Biomarkers with significant explanatory value for Clinical Response, NurOwn and Placebo NurOwn Phase 3 Description Published relationships Baseline Post Mechanism of Action CSF levels correlate with value baseline ALS survival ENCALS Model* -- MCP-1 , Δ Β-chem
Slide 19: NurOwn MOA: Lessons Learned from Phase 2, Replicated in Phase 3
NurOwn MOA: Lessons learned from Phase 2, Replicated in Phase 3 Neuroinflammation, Neurodegeneration, and Neuroprotection Biomarkers Underlying pathologies NurOwn MSC-NTF MOAs of ALS, pMS, and AD Neuroinflammation and Reduced Neuroinflammation Microglial Activation Reduces CSF MCP-1, SDF-1, S100b, M
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