23 slides from Brainstorm Cell Therapeutics's technical presentation, Dec 9, 2016
Slide 1: BrainStorm Cell Therapeutics US clinical trial BCT-001-US
ʱʡ ʣ 1 BrainStorm Cell Therapeutics US clinical trial BCT - 001 - US A Phase 2, Randomized, Double Blind, Placebo Controlled Multicenter Study to Evaluate Safety and Efficacy of Transplantation of Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors in Patients With Amyotrophic Lateral
Slide 2: The MSC-NTF cells (NurOwn) Technology
ʱʡ ʣ The MSC - NTF cells ( NurOwn ® ) Technology MSC - NTF cells are transplanted back into the patient by IT and/or IM administration MSC are induced to differentiate MSCs are expanded ex - vivo Bone marrow is harvested and MSCs are isolated from the total bone marrow population 2
Slide 3: MSC-NTF cells of ALS cases show enhanced growth factor secretion in vitro
ʱʡ ʣ Bone marrow - derived MSC - NTF cells of ALS cases show enhanced growth factor secretion in - vitro 3 Individual participant Individual participant Individual participant Individual participant GDNF BDNF VEGF HGF
Slide 4: Pilot studies of MSC-NTF in ALS showed safety and possible benefit
ʱʡ ʣ 4 Recruitment BMA Transplantation End of Study 0 2 3 9 months BMA: Bone Marrow Aspiration ↓ : Monthly visits Cohort Number of Subjects Route of Administration Number of I njection Sites Site of Administration Dose Early ALS 6 Intramuscular (IM) 24 Biceps and triceps muscles 1 x 10 6 cells/sit
Slide 5: BCT-001-US Clinical Trial of MSC-NTF in ALS Principal Investigators
ʱʡ ʣ 5 BCT - 001 - US Clinical Trial of MSC - NTF in ALS Principal Investigators Medical Center Professor Robert H. Brown Dr. Ayo Owegi Professor Merit Cudkowicz Dr. James Berry Professor Anthony Windebank Dr. Nathan Staff Three clinical trial sites:
Slide 6: BCT-001-US Clinical Trial Study Design
ʱʡ ʣ • 48 participants (16 per site) • Randomized 3:1 • Intervention – IM: 24 injections (12 into R biceps, 12 into R triceps); 2 million cells each – IT: 125 million cells in 4mL • Inpatient Observation for 48 hours • Evaluators remained blinded . Different Unblinded team delivered cells/placebo.
Slide 7: BCT-001-US Clinical Trial of MSC-NTF in ALS Endpoints
ʱʡ ʣ 7 » Primary: » Safety and tolerability » Secondary: » ALSFRS - R » Slow vital capacity (SVC) » Exploratory: » Muscle strength (HHD ) » CSF Biomarkers (added after the 1 st 8 participants) BCT - 001 - US Clinical Trial of MSC - NTF in ALS Endpoints
Slide 8: Results
$82" cell therapeutics RESULTS
Slide 9: Baseline Characteristics were balanced
ʱʡ ʣ Baseline Characteristics were balanced 9 Disposition/Demographics MSC - NTF (N=36 ) Placebo (N=12 ) Male (%) 25 (69.4) 10 (83.3) Mean Age (SD) 50.3 (11.9) 53.5 (9.11) * ITT analyses included all participants El Escorial Criteria Possible 3 (8.3) 1 (8.3) Laboratory - Supported Probable 5 (13.9
Slide 10: Treatment with Cells Appears Safe and Tolerable
ʱʡ ʣ Treatment with Cells Appears Safe and Tolerable » No deaths » No treatment - related SAEs » No AEs led to dropouts » Common Adverse Events (Most Mild/mod severity): » Post - therapy SAEs related to disease progression (e.g. G - tubes) were more frequent in the MSC - NTF cells group. 10 Ref. T
Slide 11: Safety Conclusions
ʱʡ ʣ Safety Conclusions Carlayne E. Jackson, MD, FAAN, Professor of Neurology and Otolaryngology, Chief Medical Officer - UT Medicine San Antonio, University of Texas Health Science Center who served as the chair of the Data Safety Monitoring Board on this study: " Patients in the Brainstorm study
Slide 12: Pre-specified ALSFRS-R efficacy analyses in Statistical Analysis Plan
ʱʡ ʣ Pre - specified ALSFRS - R efficacy analyses in Statistical Analysis Plan 12 » Mean change in slope pre - vs post - treatment » Responder Analysis (% of subjects with slowing post - tx ) » Subgroup analyses ▪ Excluding slow progressors ▪ “Slow” defined as ≤ 2 points decline in ALSFRS - R from
Slide 13: More people in the cell therapy group were responders
ʱʡ ʣ 13 p - values using one - sided Fishers Exact Test Given the exploratory nature of this study, statistical significance was defined as a one - sided p value < 0.1 (these p - values are highlighted in red above). In order to see trends in the data p - values that are ≥ 0.1 and < 0.2 are also h
Slide 14: More people in the cell therapy group were responders (Halt of decline or improvement)
ʱʡ ʣ 14 More people in the cell therapy group were responders (Halt of ALSFRS - R decline or improvement) 26 of 35 5 of 11 19 of 35 4 of 11 12 of 35 4 of 11 10 of 35 1 of 12 7 of 35 0 of 12 4 of 35 0 of 12 T P T P T P T P T P T P 2wks 4wks 8wks 12wks 16wks 24wks T – Treatment; P – Placebo one - si
Slide 15: Excluding slow progressors: many more responders in cell therapy group
ʱʡ ʣ Excluding slow progressors Many more people in the cell therapy group were responders (Halt of ALSFRS - R decline or improvement) 15 p - values are one - sided from Fisher's Exact test one - sided p value < 0.1 considered significant (exploratory study) 0% 10% 20% 30% 40% 50% 60% 70% 80% 2 Wk
Slide 16: Responder analysis on change in ALSFRS-R score excluding slow progressors
ʱʡ ʣ 16 0 10 20 30 40 50 60 70 80 2 Wks 4 Wks 8 Wks 12 Wks 16 Wks 24 Wks % responders ≥ 0 ALSFRS - R score Responder analysis on ≥ 0 change in ALSFRS - R Total score Excluding Slow Progressors (pre - treatment change ≥ - 2 ) MSC-NTF Placebo p= 0.005 0 10 20 30 40 50 60 70 80 2 Wks 4 Wks 8 Wks 12 W
Slide 17: ALSFRS-R Slope Improved Following Cell Therapy
ʱʡ ʣ ALSFRS - R Slope Improved Following Cell Therapy 17 -1 -0.5 0 0.5 1 1.5 2 -12wks 2wks 4wks 8wks 12wks 16wks 24wks Mean change in ALSFRS - R slope Treatment Placebo Post - treatment - pre treatment slope Pre - treatment Ref. Tables 14.2.1.1 14.2.1.4., 14.2.1.5, 14.2.1.6, 14.2.1.10, 14.2.1.11
Slide 18: Excluding slow progressors: cell therapy produced more marked improvement of slope
ʱʡ ʣ Excluding slow progressors Cell therapy produced more marked improvement of ALSFRS - R slope of decline 18 15 treated at all time - points. 5 placebo at weeks 2, 4 and 8 and 6 placebo at weeks 12, 16 and 24 -2 -1 0 1 2 3 4 Pre Transpl. 2 Wks 4 Wks 8 Wks 12 Wks 16 Wks 24 Wks Mean change in ALS
Slide 19: Cerebrospinal Fluid (CSF) analyses
ʱʡ ʣ Cerebrospinal Fluid (CSF) analyses 19 » Analyses of the CSF (to which the cells were injected) confirm the presence of the cells and their biological activity » A significant increase in neurotrophic factors (secreted by the cells) and decrease in inflammatory factors, was observed post - tra
Slide 20: Cell therapy increased levels of neurotrophic factors in CSF
ʱʡ ʣ 20 Cell therapy increased levels of neurotrophic factors in CSF MSC - NTF n = 26 Placebo n = 9 Average “ SEM * p< 0.05 ** p< 0.01 *** p< 0.001 0 100 200 300 400 500 600 700 800 900 1000 pg/ml VEGF V5 V6 * 0 100 200 300 400 500 600 700 800 900 1000 pg/ml VEGF V5 V6 0 100 200 300 400 500 600 pg
Slide 21: Cell therapy decreased some inflammatory markers in CSF
ʱʡ ʣ Cell therapy decreased some inflammatory markers in CSF 21 Average “ SEM ** p<0.01 *** p< 0.001 Monocyte chemoattractant protein - 1 ( MCP - 1 ), induces chemotaxis of macrophages and microglia, leading to pathological microgliosis and inflammatory activation Macrophage Inflammatory Proteins
Slide 22: Conclusions
ʱʡ ʣ Conclusions 22 » Achieved primary objective - MSC - NTF cells safe and well tolerated . » Related AEs almost exclusively mild/moderate : » L ocal discomfort and systemic reactions following transplant » Clinical meaningful changes in ALSFRS - R » Statistically significant in pre - specified s
Slide 23: Thank You!
ʱʡ ʣ 23 Thank You! BrainStorm : Chaim Lebovits Yael Gothelf PhD Revital Aricha PhD Yossef Levy PhD Munish Mehra PhD Eldad Melamed MD Dani Offen PhD UMass: Robert Brown, MD Ayo Owegi , MD Cat Doughtright Diane McKenna - Yasek Colin Quinn, MD Mass General : Merit Cudkowicz , MD James Berry, MD Melis