Capricor Therapeutics, Inc. · NASDAQ:CAPR
Capricor Therapeutics — Investor Presentation (January 2020)
36 slides from Capricor Therapeutics's investor presentation, January 2020
Slide 1: Corporate & Investor Presentation
Corporate & Investor Presentation January 2020 NASDAQ: CAPR
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: Developing Cell and Exosome-Based Therapies for Rare Diseases
Developing Cell and Exosome-Based Therapies for Rare Diseases RARE DISEASE FOCUS DOMAIN EXPERTISE • Preclinical Stage: Exosome platform • Comprehensive preclinical characterization technology in active development • Expertise in cell and exosome-based • Advanced Clinical Program: Cell Therapy therap
Slide 4: The Field of Exosomes: Increasing Market Opportunity
The Field of Exosomes: Increasing Market Opportunity Global market size projected to grow at high rates Increasing financing activity among private companies: Over $300M raised to date in several private companies M&A activity continuing to increase: Delivery Roche collaboration with Pur
Slide 5: Delivery of Gene-based Therapies to Treat Disease
Delivery of Gene-based Therapies to Treat Disease Problems Possible Solutions Gene therapy using viral delivery Exosomes: (AAV) ‒ nature’s delivery vehicle ‒ Immune response ‒ low immunogenicity Delivery of RNAs ‒ Uptake to render biologic relevance ‒ can deliver contents to the nucleus without
Slide 6: Why Engineer Exosomes?
Why Engineer Exosomes? • Engineering exosomes loaded with bioactive molecules potentially will: ‒ increase potency ‒ reduce variability ‒ eventually help during product development • Different modifications are now under evaluation: ‒ Cargo – Nucleic acids (mRNA or miRNAs) ‒ Membrane modifications –
Slide 7: Targeted Exosome Platform Allows for Broad Applicability
Targeted Exosome Platform Allows for Broad Applicability Regenerative Specific Tropism Loaded XOs Medicine 2.0 • Modify XO membrane • XO loaded with • Immunomodulation • Targeted delivery therapeutic cargo • Tissue regeneration Surface- CDC-XO Engineered Modified (Exosomes) Exosomes Exosomes 7
Slide 8: Loading miRNAs into Exosomes
Loading miRNAs into Exosomes MicroRNAs (miRNAs) are a class of small, noncoding RNAs involved in regulation of gene expression Loading XOs with miRNAs may allow for tunable regulation of gene expression in target cells 8
Slide 9: Capricor's Exosome Product Pipeline
Capricor’s Exosome Product Pipeline Development Phase Target Candidate Indications Discovery Preclinical Phase I Status EC-XO Inflammatory Target IND submission in 2020 (expanded culture XOs) diseases Engineered XOs Small RNA Loading Evaluating Target IND submission (siRNAs, miRs, sgRNAs) Engineered
Slide 10: EC-XOs: Mechanism of Action
Immunomodulatory Anti-inflammatory EC-XOs: Mechanism Anti-fibrotic Anti-apoptotic of Action Angiogenic Regenerative 10
Slide 11: Comparison of CDC-XO vs MSC-XOs Reveal Different Cargo
Comparison of CDC-XO vs MSC-XOs Reveal Different Cargo Exosomes surface expression profile (MACSplex) CDC #1.1 CDC #1.2 High Exosomes RNA-Seq Read counts (type) CDC #2.1 CDC #2.2 CDC #3.1 CDC #3.2 MSC #1 MSC #2 Low Exosomes surface markers miRNA clustering analysis (RNA-Seq) CDC-exosomes MSC-exosome
Slide 12: Exosomes: POC Established in Multiple Indications
Exosomes: POC Established in Multiple Indications GVHD DUCHENNE MUSCULAR DYSTROPHY* 8 8 Score GVHD Score 6 6 G V H D S c o re GVHD 4 4 V e h ic le Vehicle Low dose H ig h D o s e Low dose High dose 2 2 21 28 35 42 49 56 21 28 35 42 49 56 Days Day XOs reduce GVHD score and increase weight and XOs imp
Slide 13: Exosomes Lyophilization
Exosomes Lyophilization Particle size In vitro bioactivity In vivo bioactivity miRNA stability Macrophage activity AMI model Lyophilized CDC-XO show : • Good conservation of miRs 146a and 210 • Similar particle size and concentration post lyophilization • Similar results in-vitro and in-vivo to UFC
Slide 14: CAP-1002 Duchenne Muscular Dystrophy Program
CAP-1002 Duchenne Muscular Dystrophy Program 14
Slide 15: Lack of Dystrophin Predisposes Muscle to Damage
Lack of Dystrophin Predisposes Muscle to Damage • Dystrophin is a structural protein located within the muscle fiber membrane Whole Muscle • Acts both as a cushion and a kind of glue Tissue • Without dystrophin, muscles are unable to function properly, suffer progressive damage and Muscle-Fiber even
Slide 16: Capricor's Addressable Market
Capricor’s Addressable Market CAPRICOR’s Targeted Patient Population 16
Slide 17: Competitive Landscape for DMD
Competitive Landscape for DMD Options Challenges CAP-1002 Benefits EXONDYS 51 –13% of DMD population Immunomodulatory Exon Skipping Gene therapy – potential safety Anti-fibrotic Gene therapy risks Pro-regenerative NF-kB NF-kB inhibition may not be enough Cellular Energy Steroids Steroids have advers
Slide 18: Primary Efficacy Endpoint
Primary Efficacy Endpoint Performance of the Upper Limb (PUL: v1.2) 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
Slide 19: Capricor's CAP-1002 Technology
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 and prote
Slide 20: Mechanism of Action Defined in Stem Cell Reports
Mechanism of Action Defined in “Stem Cell Reports” phospho-Akt HO-1 GCLC cat. sub. Oxidative Nrf2 (cytoplasmic) Stress catalase SOD-2 Nrf2 (nuclear) phospho-IkB CD68+ macrophages Inflammation NF-kB p65 (nuclear) MCP1 CD3+ T cells collagen I Fibrosis collagen III mitoc
Slide 21: CAP-1002: Supporting the Mechanism of Action
CAP-1002: Supporting the Mechanism of Action Purity: miR-#1 Identity: miR-#2 Potency miR-#3 Non-Potent Potent Non-Potent Potent MSC-XO CDC-XO MSC-XO CDC-XO Non-Potent Potent CAP-1002’s purity, identity and potency can be defined by specific miRNAs 21
Slide 22: 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 23: 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 24: 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 RESULTS • Reduction in cardiac scar
Slide 25: HOPE-Duchenne: Reduced Cardiac Scar & Improved PUL
HOPE-Duchenne: Reduced Cardiac Scar & Improved PUL Scar INFERIOR IMPROVEMENT WALL R.G. Victor et al., AHA LBCT 2017; M. Taylor et al., submitted *p-values are based on absolute change from baseline 25
Slide 26: HOPE-2 Phase II Clinical Study
HOPE-2 Phase II Clinical Study 26
Slide 27: 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 28: 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 29: Improvements in PUL 2.0
Improvements in PUL 2.0 CAP-1002 vs. Placebo at 6-months n=8 p=0.0247 n=10 Improvement n=6 n=10 Δ 1.8 difference in CAP-1002 vs. placebo at 6-months • As shown by these data, preservation of function is maintained for at least 6 months. • CAP-1002 may offer a treatment for a primarily non-ambulant D
Slide 30: Improvements in Pulmonary Function Observed
Improvements in Pulmonary Function Observed n=10 n=6 n=8 n=6 n=8 n=10 n=10 n=10 • Pulmonary endpoints are intriguing: • More patients and longer follow-up may potentially lead to more robust findings • Data suggests respiratory muscle function is improved in CAP-1002 vs. placebo • No changes in FVC
Slide 31: Cardiac Function as Measured by MRI
Cardiac Function as Measured by MRI Improvement in Anterior & Lateral Systolic Wall Thickening Improvement Improvement 0 0 n=5 n=6 n=5 n=6 Similar improvements as shown in HOPE-Duchenne Analysis done using July Per Protocol population dataset. Colored boxes heights either positive or negative repres
Slide 32: HOPE-2 Interim Analysis Safety Results
HOPE-2 Interim Analysis Safety Results A total of 57 infusions were With the exception of two serious adverse events1,2 in the form performed in of immediate allergic reactions, no early safety signals were HOPE-2 as of July identified 31, 2019 To reduce the risk of such events, Capricor Since initi
Slide 33: Conclusions and Future Directions
Conclusions and Future Directions CAP-1002 for DMD Conclusions Moving Forward • Phase III clinical trial in pre-FDA • First placebo-controlled trial showing planning stages (est. 70 pts.) upper limb functional improvements in non-ambulant DMD patients • Continue discussions with FDA regarding path f
Slide 34: Market Statistics and Revenue Projections
Market Statistics and Revenue Projections CAP-1002 for DMD Patient Population Revenue Projections • Est. US DMD population: 15,000 $1,400 • Est. non-ambulant patient $1,200 population*: 50% $1,000 • Est. addressable patients*: 7,500 $800 Millions Estimated Target Price* $600 • CAP-1002 Target Price:
Slide 35: World-Class DMD Advisory Board
World-Class 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
Slide 36: Senior Leadership Team
Senior Leadership Team Linda Marbán, Ph.D. Karen Krasney, JD Chief Executive Officer, Co-founder and Director EVP & General Counsel Under her direction, Capricor has secured over $45 million in non- Ms. Krasney’s career spans over 40 years and has been focused on dilutive funding and over $50 millio
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