Capricor Therapeutics, Inc. · NASDAQ:CAPR
Capricor Therapeutics — Corporate Update (May 2020)
34 slides from Capricor Therapeutics's corporate update, May 13, 2020
Slide 1: A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients with DMD [HOPE-2]
A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients with Duchenne Muscular Dystrophy [HOPE-2] 12-month Top-Line Final Study Results May 13, 2020 Conference Call NASDAQ: CAPR 1
Slide 2: Forward-Looking Statements
Forward-Looking Statements Statements in this presentation regarding the efficacy, safety, and intended utilization of Capricor's product candidates; the initiation, conduct, size, timing and results of discovery efforts and clinical trials; the pace of enrollment of clinical trials; plans regarding
Slide 3: Call Participants
Call Participants • Linda Marban, Ph.D. – Chief Executive Officer, Capricor Therapeutics, Inc. • Craig McDonald, M.D., Professor and Chair of the Department of Physical Medicine and Rehabilitation and Director of the Neuromuscular Disease Clinics at the University of California, Davis. Dr. McDonald
Slide 4: Capricor's Regulatory Designations - DMD
Capricor’s Regulatory Designations - DMD GOAL OF FDA’S RMAT DESIGNATION To facilitate efficient development and expedite review of a drug Similar to breakthrough therapy designation: • RMAT provides benefits that include more frequent meetings with FDA to discuss the development plan for the product
Slide 5: CAP-1002 Mechanism of Action
CAP-1002 Mechanism of Action Immunomodulation ‒ Allogeneic cardiosphere-derived cells (CDCs) ‒ MOA: cells secrete exosomes: ‒ Contain miRNAs, other non-coding RNAs and proteins ‒ Internalized by target cells ‒ Strongly immunomodulatory ‒ 3 known miRNAs drive CAP-1002 potency ‒ Strong safety record i
Slide 6: Immunomodulatory Effects of CAP-1002
Immunomodulatory Effects of CAP-1002 CDCs: Cardiosphere-derived cells Macrophages Proinflammatory Systemic Inflammation 1. Cardiac inflammation Cytokines 2. Lung inflammation Effector T-cells 3. Cardiomyocyte death Multiorgan dysfunction 4. Cardiac dysfunction IFN-γ, TNFα, IL-1β, IL-6, IL-8, CXCL10,
Slide 7: Trajectory of CDCs in DMD (Preclinical Data)
Trajectory of CDCs in DMD (Preclinical Data) • Hypothesis: CDCs to treat cardiomyopathy • Left ventricular ejection fraction markedly improved vs. control – P<0.05 at all timepoints through 12 weeks of follow-up* • Hypothesis: CDCs to treat skeletal muscle function • Exercise performance approximate
Slide 8: HOPE-Duchenne (Phase I/II Results)
HOPE-Duchenne (Phase I/II Results) Reduced Cardiac Scar and Improved PUL Scar INFERIOR WALL IMPROVEMENT R.G. Victor et al., AHA LBCT 2017; M. Taylor et al., submitted *p-values are based on absolute change from baseline Capricor Therapeutics, Inc. Developing Transformative Therapies from Bench to Be
Slide 9: HOPE-2 12-Month Top-Line Final Data
HOPE-2 12-Month Top-Line Final Data Dr. Craig McDonald National PI Capricor Therapeutics, Inc. Developing Transformative Therapies from Bench to Bedside 9
Slide 10: DMD Progression is Sequential, Non-Linear and Irreversible
DMD Progression is Sequential, Non-Linear and Irreversible AGE Stages of DMD Disease Progression Example Clinical Endpoints 0 Years 5 10 15 20 25 30 Delayed & Impaired Bayley Impaired ability to NSAA Hop Run Jump Acquisition of Milestones / Rise from Floor TFTs____________ Motor Skills NSAA Loss of
Slide 11: HOPE-2 Clinical Trial
HOPE-2 Clinical Trial • Design: Phase II, randomized, double-blind, placebo-controlled trial in participants with DMD and reduced skeletal muscle function • Objective: Evaluate safety and efficacy of CAP-1002 • Dosing Regimen: 150M cells delivered intravenously every 3 months • Sites: 9 sites (USA)
Slide 12: Performance of the Upper Limb (Entry Items)
Performance of the Upper Limb (Entry Items) Target Population 0 1 2 3 4 5 6 No useful function Can use hands to Can raise 1 or 2 Can raise Can raise both Can raise both Full overhead of hands. hold pen or pick hands to mouth standardized arms to shoulder arms reach without up a coin or but cannot ra
Slide 13: Performance of the Upper Limb (PUL)
Performance of the Upper Limb (PUL) to Assess Skeletal Muscle PUL v.2.0: • 3-point response scale - more robust and reproducible than v1.2 • Compensatory strategies allowed to achieve tasks (not allowed in v1.2) • v2.0: better able to detect change at 12 months at all levels of ability* *Mayhew et a
Slide 14: Upper-Limb Skeletal Muscle
Upper-Limb Skeletal Muscle Measured by: Performance of the Upper Limb (PUL) 2.0 Performance of the Upper Limb (PUL) 1.2 Capricor Therapeutics, Inc. Developing Transformative Therapies from Bench to Bedside 14
Slide 15: Clinically Meaningful Changes Observed in PUL 2.0
Clinically Meaningful Changes Observed in PUL 2.0 (Shoulder + Mid + Distal) Mean Change from Baseline +/- SEM Mean Change from Baseline +/- SEM improvement 02 O EB 10 AC P- A PL C Δ2.4 points in CAP-1002 vs. placebo at 12-months Comparisons treated vs. placebo using mixed model repeated measures ANO
Slide 16: Individual Patient Data: PUL 2.0
Individual Patient Data: PUL 2.0 (Shoulder + Mid + Distal) PUL 2.0: Combined High-, Mid-, and Distal-Level CAP-1002 4 Change from baseline 2 MONTH 0 3 6 9 12 -2 -4 -6 -8 Comparisons treated vs. placebo using mixed model repeated measures ANOVA with covariates at baseline, 3 months, 6 months, 9 month
Slide 17: Clinically Meaningful Changes in Mid-Level PUL 1.2
Clinically Meaningful Changes in Mid-Level PUL 1.2 Similar changes shown in HOPE-Duchenne PUL 1.2 (mid) PUL 1.2 (mid) MONTH 12/ET MONTH 12/ET Mean Change from Baseline +/- SEM CAP-1002 5 0 PLACEBO 0 -2 improvement -5 -4 -10 -6 p=0.0974 (t test; two-tailed) -15 p=0.0818 -8 02 O EB 10 C P- Δ2.8 point
Slide 18: Individual Patient Data: PUL 1.2 (Mid Level)
Individual Patient Data: PUL 1.2 (Mid Level) PUL 1.2: Mid-Level Elbow Dimension PLACEBO 10 5 MONTH 0 3 6 9 12 -5 -10 -15 Comparisons treated vs. placebo using mixed model repeated measures ANOVA with covariates at baseline, 3 months, 6 months, 9 months and 12 months Capricor Therapeutics, Inc. Devel
Slide 19: Cardiac Function
Cardiac Function Measured by MRI: LV Ejection Fraction (%) LV End-Systolic Volume & LV End-Diastolic Volume CK-MB (% of total CK) Capricor Therapeutics, Inc. Developing Transformative Therapies from Bench to Bedside 19
Slide 20: Improvements in LV Ejection Fraction (%) Observed
Improvements in LV Ejection Fraction (%) Observed Potential for long-term preservation of cardiac function LV EF (%) MONTH 12/ET CAP-1002 1 PLACEBO 0 improvement -1 -2 p=0.0042 -3 Comparisons treated vs. placebo using mixed model repeated measures ANOVA with covariates at baseline, 3 months, 6 month
Slide 21: Individual Patient Data: LV Ejection Fraction (%)
Individual Patient Data: LV Ejection Fraction (%) Change from baseline Change from baseline Comparisons treated vs. placebo using mixed model repeated measures ANOVA with covariates at baseline, 3 months, 6 months, 9 months and 12 months Capricor Therapeutics, Inc. Developing Transformative Therapie
Slide 22: Improvements in LV End-Systolic Volume & LV End-Diastolic Volume Observed
Improvements in LV End-Systolic Volume & LV End-Diastolic Volume Observed LV ES Volume, Indexed, ml/m2 Mean Change from Baseline +/- SEM MONTH 12/ET CAP-1002 4 PLACEBO 2 improvement 0 improvement -2 p=0.0122 -4 Has been used as a surrogate endpoint for approval in adult heart failure Comparisons tre
Slide 23: Improvements in Creatine Kinase MB / Total Creatine Kinase (%) Observed
Improvements in Creatine Kinase MB / Total Creatine Kinase (%) Observed Enzyme associated with breakdown of cardiac muscle cells Creatine Kinase MB/Total Creatine Kinase (%) Change From Baseline 4 ✱✱✱ p=0.006 CAP-1002 3 Placebo 2 % CK-MB 1 0 improvement -1 -2 Month 12 Visit Comparisons treated vs. p
Slide 24: Individual Patient Data: Creatine Kinase MB / Total Creatine Kinase (%)
Individual Patient Data: Creatine Kinase MB / Total Creatine Kinase (%) Serum Chemistry: Creatine Kinase MB/Total Creatine Kinase (%) CAP-1002 Change from baseline 4 Change from baseline 2 0 3 6 9 12 (MONTH) -2 -4 improvement Comparisons treated vs. placebo using mixed model repeated measures ANOVA
Slide 25: Respiratory Function
Respiratory Function Measured by: Inspiratory Flow Reserve Peak Expiratory Flow (% predicted) Capricor Therapeutics, Inc. Developing Transformative Therapies from Bench to Bedside 25
Slide 26: Improvements Observed in Inspiratory Flow Reserve
Improvements Observed in Inspiratory Flow Reserve Individual Patient Data Pulmonary Function Testing: Pulmonary Function Testing: Inspiratory Flow Reserve Inspiratory Flow Reserve PLACEBO CAP-1002 0.8 0.8 Change from baseline 0.6 0.6 0.4 0.4 0.2 0.2 0.0 0.0 3 6 9 12 3 6 9 12 -0.2 -0.2 MONTH MONTH -0
Slide 27: Improvements Observed in Peak Expiratory Flow (% predicted)
Improvements Observed in Peak Expiratory Flow (% predicted) Individual Patient Data Suggested by FDA in original RMAT meeting as secondary endpoint Change from baseline Change from baseline improvement Comparisons treated vs. placebo using mixed model repeated measures ANOVA with covariates at basel
Slide 28: Safety Summary
Safety Summary Capricor Therapeutics, Inc. Developing Transformative Therapies from Bench to Bedside 28
Slide 29: HOPE-2 Safety Results
HOPE-2 Safety Results A total of 69 infusions (CAP-1002 or placebo) were performed in HOPE-2 Generally safe and well tolerated throughout the study With the exception of hypersensitivity reactions, no safety signals were identified In late December 2018, Capricor put a voluntary hold on dosi
Slide 30: HOPE-2 Safety Mitigation Efforts
HOPE-2 Safety Mitigation Efforts To reduce the risk of such future adverse events, Capricor initiated a commonly used pre-medication strategy including intravenous steroids and antihistamines to prevent or mitigate potential allergic reactions during the administration. Since the initiation of t
Slide 31: Conclusions and Future Directions
Conclusions and Future Directions Conclusions: Moving Forward: ‒ First placebo-controlled trial ‒ Requested End-of Phase 2 Meeting with showing upper limb functional FDA to discuss pathway to approval improvements in non-ambulant ‒ Engaged global CMO for scale-up of DMD patients manufacturing of CAP
Slide 32: DMD Advisory Board
DMD Advisory Board Craig McDonald, M.D. (National PI) University of California at Davis (USA) Michelle Eagle, Ph.D., M.Sc., MCSP Atom International Ltd (UK) Richard Finkel, M.D. Nemours Children's Hospital (USA) Pat Furlong Parent Project Muscular Dystrophy (USA) Kan Hor, M.D. Nationwide Children's
Slide 33: Acknowledgements
Acknowledgements All patients and their families who participated in the HOPE-2 Study Parent Project Muscular Dystrophy Coalition Duchenne CureDuchenne HOPE-Duchenne (Phase I/II) was funded with the support of CIRM Craig McDonald, MD (UC Davis) Cuixia Tian, MD (CCHMC) Russell Butterf
Slide 34: Thank you Questions and Answer
Thank you Questions and Answer Capricor Therapeutics, Inc. Developing Transformative Therapies from Bench to Bedside 34