Capricor Therapeutics, Inc. · NASDAQ:CAPR
Capricor Therapeutics — Investor Presentation (November 2019)
34 slides from Capricor Therapeutics's investor presentation, Nov 14, 2019
Slide 1: Corporate & Investor Presentation November 2019
NASDAQ : CAPR Corporate & Investor Presentation November 2019
Slide 2: Forward-Looking Statements
Forward - Looking Statements 2 Statements in this press release 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 r
Slide 3: Developing Therapies for Rare Diseases
Developing Therapies for Rare Diseases RARE DISEASE FOCUS STRATEGIC COLLBORATIONS DOMAIN EXPERTISE FINANCIAL • Advanced Clinical Program: Cell Therapy (CAP - 1002) for Duchenne muscular dystrophy (DMD) • Preclinical Stage: Exosome platform technology • RMAT, orphan drug and rare pediatric designatio
Slide 4: Capricor's Product Pipeline
Capricor’s Product Pipeline 4 Candidate Indication Development Phase Status Preclinical Phase I Phase II Phase III CAP - 1002 (allogeneic CDCs) Duchenne Muscular Dystrophy • Orphan Drug, Rare Pediatric Disease and RMAT Designations • HOPE - Duchenne: Phase I/II published in Neurology • HOPE - 2 : Ph
Slide 5: Manufacturing
5 CAP - 1002 Manufacturing CSps CDCs Wash Formulate Fill CAP - 1002 • CAP - 1002 is manufactured from donor hearts via a proprietary process • Clinical trial material currently produced at Capricor facility • High - yield process in advanced development • Previous 3 - year collaboration with Janssen
Slide 6: Duchenne Muscular Dystrophy Program
CAP - 1002 Duchenne Muscular Dystrophy Program 6
Slide 7: Lack of Dystrophin Predisposes Muscle to Damage
Lack of Dystrophin Predisposes Muscle to Damage 7 • Dystrophin is a structural protein located within the muscle fiber membrane • Acts both as a cushion and a kind of glue • Without dystrophin, muscles are unable to function properly, suffer progressive damage and eventually die • Much of the muscle
Slide 8: Capricor's Addressable Market
Capricor’s Addressable Market 8 CAPRICOR’s Targeted Patient Population
Slide 9: Primary Efficacy Endpoint PUL v.2.0
Primary Efficacy Endpoint 9 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 al, 2019; Pane et al, 2018. Pe
Slide 10: Capricor's Technology: Allogeneic Cardiosphere-Derived Cells
Capricor’s CAP - 1002 Technology CAP - 1002 is a biologic consisting of allogeneic cardiosphere - derived cells (CDCs) • Manufactured from donated heart muscle • Does not act by “stemness” - the cells do not engraft into host tissue • MOA: cells secrete exosomes: ‒ Contain miRNA, non - coding RNAs a
Slide 11: Supporting the Mechanism of Action
CAP - 1002: Supporting the Mechanism of Action Potent Non - Potent Potency miR - #3 Potent Non - Potent MSC - XO CDC - XO Purity: miR - #1 Potent Non - Potent MSC - XO CDC - XO Identity: miR - #2 11 CAP - 1002’s purity, identity and potency can be defined by specific miRNAs
Slide 12: Treatment Options for DMD are Limited
Treatment Options for DMD are Limited 12 We believe CAP - 1002 may be used synergistically with other therapeutics aimed to treat DMD Exon Skipping Gene therapy Utrophin NF - kB Steroids Options Challenges CAP - 1002 Benefits EXONDYS 51 – 13% of DMD population Gene therapy – potential safety risks U
Slide 13: Trajectory of CDCs in DMD (Preclinical Data)
Trajectory of CDCs in DMD (Preclinical Data) 13 • 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 appro
Slide 14: DMD: HOPE-Duchenne
CAP - 1002: DMD HOPE - Duchenne TARGET : DMD - related cardiomyopathy HYPOTHESIS : CAP - 1002 may also treat skeletal muscle
Slide 15: Capricor's Regulatory Designations - DMD
Capricor’s Regulatory Designations - DMD 15 Similar to breakthrough therapy designation: • RMAT provides benefits that include more frequent meetings with FDA to discuss the development plan for the product candidate • Eligibility for rolling review and priority review Products may also be eligible
Slide 16: HOPE-Duchenne Focused on Older DMD Patients
HOPE - Duchenne Focused on Older DMD Patients • Phase I/II study: 25 patients, randomized and open - label • One - time, multi - vessel, intracoronary delivery of cells • HOPE population were all on stable corticosteroids • Very limited options for this patient population https://n.neurology.org/con
Slide 17: HOPE-2: Phase II Clinical Study
HOPE - 2: Phase II Clinical Study
Slide 18: 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 site
Slide 19: Performance of the Upper Limb Entry Items
0 1 2 3 4 5 6 No useful function of hands. Can use hands to hold pen or pick up a coin or drive a powered Chair Can raise 1 or 2 hands to mouth but cannot raise a cup with a 200g weight in it to mouth Can raise standardized plastic cup with 200g weight in it to mouth using both hands if necessary Ca
Slide 20: Improvements in PUL 2.0
Improvements in PUL 2.0 -2.5 -2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0 Month 3 Month 6 M e a n C h a n g e f r o m B a s e l i n e ± S D Timepoints Mid + Distal -Level PUL 2.0 PLACEBO CAP-1002 n=10 n=8 n=10 n=6 -5 -4 -3 -2 -1 0 1 2 3 Month 3 Month 6 M e a n C h a n g e f r o m B a s e l i n e ± S D Ti
Slide 21: Improvements in Grip Strength and Tip-to-Tip Pinch Strength
-6 -4 -2 0 2 4 6 8 Month 3 Month 6 M e a n C h a n g e f r o m B a s e l i n e ± S D Timepoints Tip to Tip Strength PLACEBO CAP-1002 -6 -4 -2 0 2 4 6 Month 3 Month 6 M e a n C h a n g e f r o m B a s e l i n e ± S D Timepoints Grip Strength PLACEBO CAP-1002 Improvements in Grip Strength and Tip - to
Slide 22: Improvements in Pulmonary Function Observed
-30 -25 -20 -15 -10 -5 0 5 10 15 20 Month 3 Month 6 M e a n C h a n g e f r o m B a s e l i n e ± S D Timepoints PEF Percentage Predicted PLACEBO CAP-1002 -0.3 -0.2 -0.1 0.0 0.1 0.2 0.3 0.4 Month 3 Month 6 M e a n C h a n g e f r o m B a s e l i n e ± S D Timepoints IFR PLACEBO CAP-1002 Improvements
Slide 23: Cardiac Function as Measured by MRI
-12 -7 -2 3 8 Month 6 M e a n C h a n g e f r o m B a s e l i n e ± S D Timepoint Systolic Wall Thickening -Anterior PLACEBO CAP-1002 -12 -7 -2 3 8 Month 6 M e a n C h a n g e f r o m B a s e l i n e ± S D Timepoint Systolic Wall Thickening -Lateral PLACEBO CAP-1002 Cardiac Function as Measured by M
Slide 24: Increase in Left Ventricle Myocardium Mass
Increase in Left Ventricle Myocardium Mass 24 n=6 n=5 Analysis done using July Per Protocol population dataset. Colored boxes heights, either positive or negative, represent mean change from baseline. Bars represent ± one standard deviation from the mean.
Slide 25: HOPE-2 Interim Analysis Safety Results
HOPE - 2 Interim Analysis Safety Results 25 1 Assessed as related to either CAP - 1002 or placebo administration 2 One SAE each in HOPE - 2 and HOPE - OLE With the exception of two serious adverse events 1,2 in the form of immediate allergic reactions, no early safety signals were identified A total
Slide 26: Conclusions and Future Directions
Conclusions and Future Directions • First placebo - controlled trial in DMD to use PUL 2.0 for evaluation of efficacy • First placebo - controlled trial showing upper limb functional improvements in non - ambulant DMD patients • Directionally consistent improvements in function, strength, pulmonary
Slide 27: DMD Market Statistics and Revenue Projections
DMD Market Statistics and Revenue Projections Patient Population • Est. US DMD population: 15,000 • Est. non - ambulant patient population*: 50% • Est. addressable patients*: 7,500 Estimated Target Price* • CAP - 1002 Target Price: $150,000 per dose ‒ Current dosing estimate: 4 doses per year = $600
Slide 28: World-Class DMD Advisory Board
World - Class DMD Advisory Board 28 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. Natio
Slide 29: Exosomes – Nature's Communication System
Exosomes – “Nature’s Communication System” • Extracellular vesicles - term for cell - derived vesicles, includes exosomes and microvesicles • Nanometer - sized lipid - bilayer vesicles (30 - 120nm) • Rich in RNAs and proteins • Secreted by nearly all cell types • Cell signaling modality • Potential
Slide 30: Exosomes Recapitulate CDC Therapeutic Effect
Exosomes Recapitulate CDC Therapeutic Effect Ibrahim et al, Stem Cell Reports, 2014. • CDC - XOs Improve Cardiac Function and Preserve Muscle Mass 30 25 30 35 40 45 50 1 15 30 EF (%) Days post MI Control CDC-XO NHDF-XO MSC-XO ** * 0 5 10 15 20 CTRL NHDF-XO MSC-XO CDC-XO Scar Mass (mg) ** ** * CTRL N
Slide 31: Exosomes: POC Established in Multiple Indications
31 Exosomes: POC Established in Multiple Indications GVHD LUPUS NEPHRITIS SEPSIS DUCHENNE MUSCULAR DYSTROPHY* F4/80 + CD11b + Macrophage: 46.5% Macrophage: 14.5% 21 28 35 42 49 56 2 4 6 8 Day G V H D S c o r e Vehicle Low dose High Dose 21 28 35 42 49 56 Days 8 6 4 2 GVHD Score GVHD Score Vehicle Lo
Slide 32: CDC-Exosomes Demonstrate Preferential Uptake by Satellite Cells
CDC - Exosomes Demonstrate Preferential Uptake by Satellite Cells Control CDC - exosomes mdx + CDC - exosomes WT + CDC - Exosomes • Myofibers isolated from WT or mdx 4cv mice were incubated O/N with CFSE labeled exosomes from CDCs • Fibers were stained for ATPB, a mitochondria marker ( Exp #1) or fo
Slide 33: Investment Highlights
Regulatory Pathway • First - in - class biologics with potential to improve cardiac and skeletal muscle • Product candidates based on cells and extracellular vesicles (exosomes) • HOPE - 2, Phase II trial in DMD ongoing • Commercial manufacturing process in development • Positive proof - of - concep
Slide 34: Senior Leadership Team
Senior Leadership Team Linda Marbán , Ph.D. Chief Executive Officer, Co - founder and Director Under her direction, Capricor has secured over $45 million in non - dilutive funding and over $50 million in equity capital. Earlier in her career, Dr. Marbán was with Excigen, Inc. where she was responsib
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