CORPORATE & INVESTOR PRESENTATION - NASDAQ: CAPR - Capricor Therapeutics

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CORPORATE & INVESTOR PRESENTATION - NASDAQ: CAPR - Capricor Therapeutics
CORPORATE
& INVESTOR
PRESENTATION

               NASDAQ: CAPR
CORPORATE & INVESTOR PRESENTATION - NASDAQ: CAPR - Capricor Therapeutics
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 regulatory filings, future research and clinical trials; regulatory developments involving products, including
the ability to obtain regulatory approvals or otherwise bring products to market; the ability to achieve product milestones
and to receive milestone payments from commercial partners; plans regarding current and future collaborative activities
and the ownership of commercial rights; scope, duration, validity and enforceability of intellectual property rights; future
royalty streams, revenue projections; expectations with respect to the expected use of proceeds from the recently
completed offerings and the anticipated effects of the offerings, and any other statements about Capricor's management
team's future expectations, beliefs, goals, plans or prospects constitute forward-looking statements within the meaning of
the Private Securities Litigation Reform Act of 1995. Any statements that are not statements of historical fact (including
statements containing the words "believes," "plans," "could," "anticipates," "expects," "estimates," "should," "target,"
"will," "would" and similar expressions) should also be considered to be forward-looking statements. There are a number of
important factors that could cause actual results or events to differ materially from those indicated by such forward-looking
statements. More information about these and other risks that may impact Capricor's business is set forth in Capricor's
Annual Report on Form 10-K for the year ended December 31, 2021 as filed with the Securities and Exchange Commission
on March 11, 2022. All forward-looking statements in this press release are based on information available to Capricor as of
the date hereof, and Capricor assumes no obligation to update these forward-looking statements.
CAP-1002 is an Investigational New Drug and is not approved for any indications. None of Capricor’s exosome-based
candidates have been approved for clinical investigation.

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                              2
CORPORATE & INVESTOR PRESENTATION - NASDAQ: CAPR - Capricor Therapeutics
Capricor Therapeutics
Company Highlights NASDAQ: CAPR
  Cell and Exosome-Based Platform Therapeutics Company
  Commencing Phase 3 in Duchenne Muscular Dystrophy
  • Strategic partnership: $705 million in potential milestones
  • Market potential over $1 billion annual sales
  • Positive phase 2 data published in The Lancet
  Exosomes Platform Expansion
  • Natural intracellular delivery technology for RNA and proteins
  Broad Scientific and Intellectual Property Profile                                      Headquarters: San Diego, California
  • Over 100 publications from multiple institutions worldwide                            NASDAQ: CAPR
                                                                                          Founded: 2006, public in 2013
  • 100 patents and patent applications                                                   Outstanding Shares: 24.3M
  Strong External Collaborations                                                          Employees: 50

  • US Army, US Department of Defense, Stephen Gould, Ph.D. Laboratory at Johns Hopkins
    University, Cedars-Sinai Medical Center and Nippon Shinyaku, Co.
  Cash Runway for over 2 Years

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                         3
CORPORATE & INVESTOR PRESENTATION - NASDAQ: CAPR - Capricor Therapeutics
Capricor’s Recent Achievments
    Cell Therapy Program in Duchenne Muscular Dystrophy
    • Entered exclusive partnership with Nippon Shinyaku, Co. for U.S. distribution rights
            • Received $30 million, additional $705 million in potential milestones plus revenue share
    • Phase 2 data published in The Lancet
    • Phase 3 pivotal study cleared by FDA to proceed
    • Orphan Drug, RMAT and Rare Pediatric Disease Designations
    Engineered Exosomes Platform Expansion
    • Signed exclusive, worldwide licensing agreement with Johns Hopkins University for vaccines
      and therapeutics
    • Published new advances in exosome mRNA delivery
    Relocation and Expansion of Senior Leadership Team
    • Relocated headquarters to San Diego, California

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                  4
CORPORATE & INVESTOR PRESENTATION - NASDAQ: CAPR - Capricor Therapeutics
Capricor’s Product Pipeline
                                   Target                                                 Development Phase
  Candidate                        Indications                 Discovery          Preclinical   Phase I   Phase II   Phase III   Status
  CAP-1002                         Duchenne Muscular
                                                                                                                                 Phase III initiating Q2 2022
  (allogeneic CDCs)                Dystrophy

  Exosome-Based Vaccine
                                   Infectious diseases                                                                           Preclinical
  (Multivalent design)

  Engineered Exosomes
                                   Undisclosed                                                                                   Discovery
  (RNA and protein delivery)

  CDC-Exosomes                     Duchenne Muscular
                                                                                                                                 IND submitted
  (allogeneic CDC-XOs)             Dystrophy

      Cell Therapy            Exosome Platform

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                                                         5
CORPORATE & INVESTOR PRESENTATION - NASDAQ: CAPR - Capricor Therapeutics
Capricor’s CAP-1002 Cell Therapy Technology

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   6
CORPORATE & INVESTOR PRESENTATION - NASDAQ: CAPR - Capricor Therapeutics
Capricor’s Cell Therapy Technology
CAP-1002

         CAP-1002: biologic consisting                                                    Manufactured
         of allogeneic cardiosphere-                                                      from donated heart muscle
         derived cells (CDCs)
                                                                                          Does not act by «stemness»
         Has been investigated in                                                         the cells do not engraft into host tissue
         multiple independent clinical
         trials and approximately                                                         Mechanism: cells secrete exosomes:
         200 human subjects to date                                                       • Contain miRNAs, non-coding RNAs and
                                                                                            proteins
                                                                                          • Internalized by target cells
                                                                                          • Stimulate diverse and lasting changes
                                                                                            in cellular behavior
                                                                                          • 3 known miRNAs drive CAP-1002 potency

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                               7
CORPORATE & INVESTOR PRESENTATION - NASDAQ: CAPR - Capricor Therapeutics
CAP-1002 Mechanism of Action: Defined
                                              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

                                              mitochondrial DNA copy number                                RESTORED mitochondrial ultrastructure
      Cellular Energy                                                                                       NORMALIZED deficient respiratory capacity
                                              level of respiratory chain subunits                                      of isolated mitochondria

                                              Ki67+ cardiomyocytes
         Muscle Cell
         Generation                           Aurora B cardiomyocytes

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                               Aminzadeh, et al. Stem Cell Reports. 2018.   8
CORPORATE & INVESTOR PRESENTATION - NASDAQ: CAPR - Capricor Therapeutics
CAP-1002
  Supporting the Mechanism of Action

               Purity: miR-#1                                           Identity: miR-#2                         Potency miR-#3
                              Non-Potent         Potent                                  Non-Potent     Potent

        MSC-EXO                     CDC-EXO                           MSC-XO                  CDC-EXO            Non-Potent   Potent

                       CAP-1002’s purity, identity and potency can be defined by specific miRNAs

Capricor Therapeutics, Inc.      Developing Transformative Therapies from Bench to Bedside                                             9
CORPORATE & INVESTOR PRESENTATION - NASDAQ: CAPR - Capricor Therapeutics
Duchenne Muscular Dystrophy
CAP-1002 Cell Therapy Technology

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   10
Duchenne Muscular Dystrophy
Market Opportunity
    Duchenne Muscular Dystrophy: the most severe form of muscular dystrophy
       • X-linked genetic disorder
       • Unable to produce dystrophin: essential protein for muscle formation and
          growth
       • Deficiency leads to loss of ambulation; severe cardiac and respiratory symptoms
       • Approx. 20,000 cases in United States, globally 1 in 3,500 male births
    Unmet Medical Need
       • No known cure; disease is fatal
       • Present standard of care involves corticosteroids
       • Very few options in development for non-ambulant patients
    CAP-1002 aims to attenuate skeletal and cardiac muscle damage
       • Clinical data demonstrates improvement in upper limb and cardiac function in
          two clinical trials

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside    11
Duchenne Muscular Dystrophy
Lack of Dystrophin Predisposes Muscle to Damage

                                                                             Dystrophin is a structural protein
                                                                             located within the muscle fiber membrane

                                                                                          Acts both as a cushion and glue

                                                                                               Without dystrophin, muscles are unable to
                                                                  Dystrophin
                                                                                               function properly, suffer progressive
                                                                                               damage and eventually die
                                 Whole
                                 Muscle
                                 Tissue                               Muscle-
                                                                        Fiber
                                                                                              Much of the muscle injury that occurs
                                                                    Membrane                  in dystrophin-deficiency is attributable to
                                                                                              secondary damage caused by inflammation

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                                     12
Capricor’s Addressable DMD Population

                                                                                          Capricor’s Targeted
                                                                                          Patient Population

                                                                                          Estimated that over 50%
                                                                                          of DMD patients in U.S.
                                                                                             are non-ambulant

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                             13
Trajectory of CAP-1002 in DMD
Preclinical Data
  HYPOTHESES
                                                CDCs to treat                        CDCs to improve         CDCs to improve                    CDCs to treat
                                                cardiomyopathy                       exercise capacity       skeletal muscle                    diaphragm
                                                Left ventricular ejection            Exercise performance    function                           muscle
                                                fraction markedly                    approximately doubled   Twitch force, tetanic force, and   Fibrosis in the diaphragm
                                                improved vs. control                 vs. control             fibrosis in soleus                 markedly declined
                                                                                                             (slow-twitch) and                  vs. control
                                                                                                             extensor digitorum
                                                                                                             longus (fast-twitch) muscles
                                                                                                             significantly improved vs.
                                                                                                             control

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                      Aminzadeh, et al. Stem Cell Reports. 2018.     14
Competitive Landscape for DMD

                                  01                          02                          03
                                  Exon                        Gene                        Steroids
         Options                  Skipping                    therapy

                                  01                          02                          03             CAP-1002
                                                                                                         Benefits
                                  Exon Skipping               Gene therapy                Steroids
         Challenges               treats a small              potential                   have adverse
                                  portion of the              safety risks                side-effects
                                  DMD population                                                         •   Immunomodulatory
                                                                                                         •   Anti-fibrotic
                                  CAP-1002                                                               •   Pro-regenerative
                                  may be used synergistically                                            •   Cellular Energy
         We believe               with other therapeutics
                                  aimed to treat DMD

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                         15
Performance of Upper Limb (PUL Test)
To Assess Skeletal Muscle Function

              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*

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   *Mayhew et al, 2019; Pane et al, 2018.   16
Capricor’s Regulatory Designations
Duchenne Muscular Dystrophy
                                                                 Products may also be eligible for
                                                                 accelerated approval
                                                                 •    RMAT provides benefits that include more frequent         01
                                                                      meetings with FDA to discuss the development plan
                                                                      for the product candidate
                                                                                                                                RMAT
     GOAL OF FDA’S                                               •    Eligibility for rolling review and priority review
                                                                                                                                Designation

     RMAT
                                                                                                                                02

                                                                                                                                Rare Pediatric
     DESIGNATION                                                 Similar to breakthrough
                                                                 therapy designation:
                                                                                                                                Disease
                                                                                                                                Designation
     To facilitate efficient                                     •    On the basis of a surrogate or intermediate endpoint      03
     development and expedite                                         reasonably likely to predict long-term clinical benefit
     review of a drug                                                                                                           Orphan
                                                                 •    Reliance upon data obtained from a meaningful
                                                                      number of sites                                           Drug
                                                                                                                                Designation

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                                          17
HOPE-Duchenne
Phase I/II Overview
    • Phase I/II study: 25 patients, randomized and open-label
    • One-time, multi-vessel, intracoronary delivery of 75M cells
    • HOPE population were all on stable corticosteroids
    • Very limited options for this patient population

      RESULTS
      • Reduction in cardiac scar at 6 and 12 months measured by MRI
      • Improvement in cardiac function (systolic wall thickening) at 6 and
        12 months
      • Improvements shown in PUL (mid + distal)
          – Best improvement shown within the first 3 months
      • Study published in February 2019 in Journal of Neurology

                                                                                                 Study funded with the support of CIRM
 Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   Results published in Neurology, 2019.         18
HOPE-Duchenne Results
Reduced Cardiac Scar and Improved PUL
                                   Scar Size                                                                              Mid+distal PUL

                                                                                      Scar

                                                         R.G. Victor et al., AHA LBCT 2017; M. Taylor et al., submitted

 Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                          Results published in Neurology, 2019.   19
HOPE-2 Phase II Design
  • 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)

  • Data: ITT population - 20 subjects

  Demographics

          • Mean age: 14.3 years

          • All patients were on corticosteroids

          • ~ 80% of patients were non-ambulant

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   Results published in The Lancet, March 2022.   20
HOPE-2 Phase 2 Results
Published in The Lancet, March 2022

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   Results published in The Lancet, March 2022.   21
HOPE-2 Upper Limb Improvements
Primary Efficacy Endpoint: PUL 1.2 Mid Level
                                                                                                                            Mid-level PUL 1.2

                                                                                                                            p=0.01

                                                                                                                                                             improvement
                                                     71% slowing of disease (PUL)                                            Δ2.6 points in CAP-1002
                                                                                                                            vs. placebo at 12-months

Mixed Model for Repeated Measures (MMRM) analysis was performed using percentile ranked change from baseline as
dependent variable and percentile ranked baseline score, treatment, visit, treatment-by-visit interaction, PUL entry-item
score at randomization, and site as model effects. Adjusted model outcomes are report as least-squares means (LS-Mean).

Capricor Therapeutics, Inc.                             Developing Transformative Therapies from Bench to Bedside                Results published in The Lancet, March 2022.   22
HOPE-2 Upper Limb Improvements
PUL 2.0 Full                                                                                                                Full PUL 2.0

                                                                                                              p=0.04

                                                                                                                                           improvement
                                                                                                                                                     Δ1.8 points in CAP-1002
                                                                                                                                                     vs. placebo at 12-months
Mixed Model for Repeated Measures (MMRM) analysis was performed using percentile ranked change from baseline as
dependent variable and percentile ranked baseline score, treatment, visit, treatment-by-visit interaction, PUL entry-item
score at randomization, and site as model effects. Adjusted model outcomes are report as least-squares means (LS-Mean).

Capricor Therapeutics, Inc.                             Developing Transformative Therapies from Bench to Bedside                                             Results published in The Lancet, March 2022.   23
HOPE-2 Cardiac Improvements
Ejection Fraction and CKMB
                                                       LV Ejection Fraction                                                 Creatine Kinase MB/ Total Creatine Kinase (%)

                                                                                                                                                                         improvement
                                      p=0.002                                                                                                           p=0.02

                                                 Δ=4% in LVEF by cardiac MRI                                                      Biomarker to assess cardiac muscle damage

Mixed Model for Repeated Measures (MMRM) analysis was performed using percentile ranked change from baseline as
dependent variable and percentile ranked baseline score, treatment, visit, treatment-by-visit interaction, PUL entry-item
score at randomization, and site as model effects. Adjusted model outcomes are report as least-squares means (LS-Mean).

Capricor Therapeutics, Inc.                             Developing Transformative Therapies from Bench to Bedside                               Results published in The Lancet, March 2022.   24
CAP-1002 Proteomic Biomarkers in DMD
                   A                                                                          B                                              Treated vs.
                                                                                                                                                             C
                                                                                                                                           Placebo (mons)

                       Blood        Protein   Detection                                       Function and Canonical pathways                 3       6
                     component       conc.    method                                          Binding of mononuclear leukocytes
                                                                                              Cell movement of natural killer cells
                                                                                              Mobilization of blood cells
                        Resident

                                                                   Mitra blood device LC-MS
                                               Dual Plasma LC-MS
                                                                                              Attraction of T-lymphocytes
                        blood
                                                                                              Migration of macrophages
                        proteins
                                                                                              Adhesion of mononuclear leukocytes                                                                                                                                   Reduced
                                     SAA
                                                                                              Recruitment of mononuclear leukocytes                         Reduced glucose                                                                                        trafficking of
                        Systemic     VWF                                                                                                                      metabolism                                                                                           leukocytes
                        response     CRP                                                      Recruitment of T-lymphocytes
                                                                                                                                                              dysfunction
                                                                                              Cell death of lympatic system cells                                                                                                                      Inhibition of
                        factors/                                                                                                                                                                                                                        neutrophils
                                     ICAM/                                                    LXR/RXR activation
                         Tissue                                                                                                                             Reduced damageto
                                                                                              Trem1 signaling in neutrophils + monocytes
                                               Cytokine ELISA

                                     VCAM
                        leakage                                                                                                                             cartilage&bone                                                                    Infection
                                     TGFB1                                                    HMGB1 signaling from monocytes +
                                                                                              macrophages                                                               Reduced
                                                                                                                                                                    proinflammatory                                                   Synthesis of
                                                                                              TH2 pathway                                                                              Decrease
                                     IL-6                                                                                                                                                                                           prostaglandin E2
                       Cytokines                                                              IL23 pathway                                                              response
                                                                                                                                                                                      functionof     Reduced       Activation of
                                                                                              Senescence pathways                                                                     leukocytes   recruitmentof   dendriticcells
                                                                                              IL8 pathway                                                                                           neutrophils
                                                                                              Acute phase response
                                                                                              NF-kB signaling

                     Panel A: Complimentary approaches required to analyze blood-based markers depending on
                     their concentration range
                     Panel B: CAP-1002 treatment alters inflammatory and immune pathways in DMD
                     Panel C: Dynamic proteomic and cytokine changes induced by CAP-1002 treatment are linked to
                     a series of downstream end-effects in DMD

Capricor Therapeutics, Inc.        Developing Transformative Therapies from Bench to Bedside                                                                                                                Results published in The Lancet, March 2022.                            25
HOPE-2 Safety Results

                                         69total infusions
                                                                                          Generally safe
                                                                                          and well tolerated throughout the study

                                                                                          With the exception of three
                                           were performed in HOPE-2                       hypersensitivity reactions;
                                                                                          no safety signals were identified

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside             Results published in The Lancet, March 2022.   26
Phase III Pivotal Trial
Cleared to Proceed by FDA

   •       HOPE-3: Phase III, randomized, double-blind, placebo-controlled trial
   •       Target Enrollment: 70 patients
   •       Number of estimated sites: 20-30
   •       Targeting: Non-Ambulant DMD patients
   •       Primary Endpoint: PUL 2.0 at 12 months
   •       Secondary Endpoints: Cardiac, QOL, clinical status
   •       Initiation and Start-up Activities: underway

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   27
Partnership with Nippon Shinyaku
Exclusive Distribution and Commercialization

Commercial Rights: CAP-1002 for the treatment of DMD
• US rights only
• Nippon to appoint NS Pharma, its US subsidiary, as exclusive sales and distribution partner

Deal Valued at up to $735M
• $30M upfront
• Up to $705M in additional development and sales milestones

Meaningful double-digit revenue share of product revenue to Capricor

Capricor responsible for the conduct of the Phase 3 trial and manufacturing of CAP-1002

Nippon Shinyaku recently launched Viltepso, an exon skipping agent for the treatment of
DMD and has a fully assembled U.S. team to support a broad commercialization effort

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside         28
World-Class DMD Advisory Board

    Craig McDonald,
                                                    Pat Furlong                            Kan Hor, M.D.                    Thomas Voit, M.D.
    M.D. (National PI)
                                                    Parent Project Muscular                Nationwide Children's Hospital   University College
    University of California                        Dystrophy (USA)                        (USA)                            London (UK)
    at Davis (USA)

    Michelle Eagle,                                 Oscar Henry Mayer,                     Eugenio Mercuri,                 Francesco Muntoni,
    Ph.D., M.Sc., MCSP                              M.D.                                   M.D., Ph.D.                      M.D.
    Atom International                              Children's Hospital                    Catholic University of           University College
    Ltd (UK)                                        of Philadelphia (USA)                  the Sacred Heart (Italy)         London (UK)

                                                                                                                            Michael Taylor,
    Richard Finkel, M.D.                            John Jefferies, M.D.                   Lee Sweeney, Ph.D.
                                                                                                                            M.D., Ph.D.
    Nemours Children’s                              Cincinnati Children's Hospital         University of Florida
    Hospital (USA)                                  Medical Center (USA)                   (USA)                            Cincinnati Children's Hospital
                                                                                                                            Medical Center (USA)

Capricor Therapeutics, Inc.    Developing Transformative Therapies from Bench to Bedside                                                                     29
Capricor’s Exosome Platform
Therapeutics and Vaccines

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   30
RNA Therapeutics
A New Class of Medicines

 Broad Market Opportunities
    Capital Efficiency for Development
         Rapid Innovation Possible
              Proof of Concept Established in Vaccines

                      Barrier to Success:
                      Effective Delivery Systems of Nucleic Acids

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   31
Exosomes are Nature’s Delivery Tool
Drug Delivery System

• ~100 nanometer vesicles
• Made by nearly all cells
• Abundant in blood and all biofluids
• Transfers signals and molecules to other cells
• Decades of transfusion and transplantation
  medicine demonstrates safety
• Can be used to deliver RNAs, proteins and
  other drugs

                                                                                                                                      Kidney International (2010) 78, 838–848

 Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   Extracellular vesicles - term for cell-derived vesicles, including exosomes 32
Exosomes Platform Development Tools

    Production                                          Loading                             Targeting                      Delivery

  • Scalable production                        • Evaluate loading                         • Unmodified for local      • Exosome targeting,
    processes in                                 requirements and size                      injection                   cargo delivery, dosing,
    development                                  constraints                              • Cell-specific targeting     safety, distribution
  • Extensive                                  • mRNA, siRNA, small                         for systemic injection    • In vitro and in vivo
    characterization of cell                     molecule, and protein                    • Potential to target         efficacy
    line                                         cargos                                     muscle, brain, etc.

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                                           33
Exosomes Potential Solutions
to Drug Delivery Challenges

                                 Problems                                                             Possible Solutions

      • Gene therapy using viral delivery (AAV)                                           Exosomes:
          • Immune response                                                                  • low immunogenicity
      • Delivery of RNAs
                                                                                             • can deliver contents to the cell
          • Uptake to render biologic relevance
                                                                                               without integration
          • Therapeutic development slow
      • Synthetic nanoparticles are untargeted                                               • can be targeted (tropism)
        delivery vehicles                                                                    • can be lyophilized for ease of
                                                                                               handling

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                           34
Targeted Exosome Platform
Allows for Broad Applicability

                                                                                          SURFACE-MODIFIED EXOSOMES
                                                                                          Specific Tropism
                                                                                          •   Modify exosome membrane
                                                                                          •   Targeted delivery
   CDC-EXOSOMES
  Regenerative Medicine 2.0
          •    Immunomodulation
           •   Tissue regeneration

                                                                                          ENGINEERED EXOSOMES
                                                                                          Loaded Exosomes
                                                                                          •    Exosomes loaded with therapeutic
                                                                                               cargo

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                           35
Exosomes as a Delivery Vehicle
Vaccine Proof of Concept

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   36
Novel Exosome-Based Vaccine Platform
Display and mRNA Technologies
   Exosome-based approach
     • Natural intracellular delivery particle
     • Allows for specificity in cellular targeting
     • Innovative technology, yet is well characterized
   Unique multi-antigen approach
     • Potentially confers greater immunity by targeting at least S and N proteins
   Exosomes potentially superior to lipid nanoparticles
     • Low immunogenicity
     • Deliver payload directly to cytoplasm
     • Target different immune cell populations to modulate their activity for
        therapeutic purposes
   Two differentiated vaccine approaches under development
     • Display and mRNA approaches

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   37
Coronavirus Structure
Unique Protein Visualization

                                                                   Spike Protein
                                                                       generates antibody response*                             Other
                                                                                                                                vaccines
Spike                                                                                                                           in development are targeting
                                                                                                                                the spike “S” protein solely
(S)

                                                                                                                                Capricor’s exosome
                                                                                                                                vaccine
                                                                                                                                Addresses both “S” and “N”
                                                                                                                                proteins
 Nucleocapsid
 (N)
                                                                                                                                Unique vaccine
                                                                                                                                approach utilizing
                                                                                                                                exosomes as delivery vehcicle
                                                                        Nucleocapsid Protein
                                                  RNA                       generates T-cell response*
                                                  viral genome

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                  *Results from Journal of Biological Chemistry, Gould, 2021.   38
Exosome: Display Vaccine Approach
Broad Potential Use in Infectious and Other Diseases

   01                            02                               03                       04                            05
   Create vectors                Transfect                        Grow the cells,          Purify the exosomes:          Immunize
   that express                  into 293 cells                   which produce            which carry the S and N       with purified VLPs,
   the SARS-CoV-2                                                 SARS-CoV-2 VLPs          proteins in their native,     including protective
   structural proteins such                                                                authentic, biochemical/cell   immunity to SARS-
   as S and N                                                                              biological context            Cov-2
                                                                                           and conformation

                                                                                                                                                Capricor’s
                                                                                                                                                exosome display
                                                                                                                                                vaccine addresses
  N
                                                                                                                                                multiple proteins
                                                                                                                                                of SARS-CoV-2
  S

 Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                                                    39
Exosome mRNA Vaccine
Preclinical Results: Cellular and Humoral Response
             Study key findings:
             •   Drives cell and antibody immunity to nucleocapsid protein (SARS-CoV-2)
             •   Drives cell and antibody immunity to spike protein (SARS-CoV-2)
             •   Confirms multiplexed mRNA approach
             •   Unique antigen design

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   Results from Journal of Biological Chemistry, Gould, 2021.   40
Exosomes Platform Goals
Building a New Class of Medicines

                                                                                                              Monogenic Diseases
                                                                                                              RNA and protein therapeutics

                                                                                                              Oncology
                                                                                                              Vaccines and targeted delivery
                                                                                                              therapeutics

                                                                                                              Inflammatory & Vascular
                                                                                                              Biologics

                                 Exosomes                              Drug Payload                           Infectious Diseases
                                                                                                              Vaccines

Cell

                                                                                          Drive research   Expand and exploit
                                                       Scale
       Goals                                           and partner
                                                                                          through          platform and IP through
                                                                                          collaborations   partnerships

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside                                                        41
Recent and Targeted Milestones
 Cash Position
    CAP-1002 for Duchenne Muscular Dystrophy
    Reported 1-year positive results from HOPE-2 at World Muscle Society
    Announced FDA acceptance of Phase 3 trial protocol and design
    Announced partnership with Nippon Shinyaku for US distribution rights
    Published Phase 2 results in The Lancet
    Phase III initiation of enrollment                                                     Q2 2022
    Pursue additional partnerships outside U.S.                                            2022-2023

    Exosomes Platform
    Entered exclusive worldwide licensing agreement with Johns Hopkins University for
    engineered exosome platform of vaccines and therapeutics
    Published positive preclinical data using multivalent exosome vaccine
    Published preclinical data in conjunction with US Army for trauma and shock
    Publish new preclinical data on platform expansion                                     2022
    Announce further pipeline expansion and indications                                    2022-2023

    Cash Position1
    $34.9 million as of 12/31/21, additional $30M upfront payment received in March 2022

Capricor Therapeutics, Inc.   Developing Transformative Therapies from Bench to Bedside   1As   reported in Form 10K filed on 03/11/22   42
Senior Leadership Team

 Linda Marbán, Ph.D.         AJ Bergmann, M.B.A.             Karen Krasney, J.D.           Daniel Paulson, M.D.     Kristi Elliott, Ph.D.                 Yasmine Shad                     Stephen Gould, Ph.D.
Chief Executive Officer,     Chief Financial Officer       Executive Vice President           Vice President of   Vice President of R&D              Vice President of Quality             Executive Consultant
Co-founder & Director        •                               & General Counsel             Clinical Development                                                                           • Dr. Gould is a Professor of
                                                                                                                  • Dr. Elliott oversees
•                                                      •                               •                            Capricor’s exosome platform      • Ms. Shad oversees all facets of      Biological Chemistry at Johns
                                                                                                                    and pipeline development.          Quality Assurance and Quality        Hopkins University
                                                                                                                                                       Control for Capricor’s product       and an internationally
                                                                                                                  • She has approximately 15           pipeline.                            recognized exosome expert
•                            •
                                                                                                                    years of experience in                                                  who brings an unparalleled
                                                                                                                    biotechnology                    • She has approximately 20 years       understanding of
                                                       •                               •                                                               of experience in the quality         exosome engineering
•                                                                                                                 • As an innovator in the             assurance field of
                                                                                                                    exosome field, Dr. Elliott has     biotechnology                      • Dr. Gould is co-Founder and
                                                                                                                    been involved in the                                                    acting President of the
                                                                                                                    conception and                   • Ms. Shad previously held the         American Society
                                                                                                                    implementation of exosome          position of Executive Director,      for Exosomes and Microvesicles
•
                                                       •                                                            purification, scale-up,            Clinical Quality, Site Head for
                             •                                                                                                                         Kite Pharma, a Gilead Company, • Dr. Gould’s team was the first
                                                                                                                    loading and targeting
                                                                                       •                            processes for multiple             where she led clinical trial stage   to reveal the mechanistic link
                                                                                                                    exosome-based product              quality functions including but      between exosome biogenesis
                                                                                                                    candidates.                        not limited to quality systems,      and virus budding, the first to
                                                                                                                                                       quality operations, quality          identify mechanisms of
                                                                                                                  • Dr. Elliott received her B.A.      engineering, LIMS, QC                exosome engineering and the
                             •
                                                                                                                    in biology and M.S. in             analytical, QC microbiology, and first to develop an exosome-
•                                                                                                                   molecular biology from             sample management.                   based cancer therapeutic
                                                                                                                    Rutgers University. She
                                                                                       •                            earned her Ph.D. in human        • Ms. Shad received her B.S. and • Dr. Gould has published
                                                                                                                    genetics and molecular             M.S. in Biochemistry from        numerous research articles and
                                                                                                                    biology from The Johns             Laurentian University and the    several book chapters, received
                                                                                                                    Hopkins School of Medicine.        University of Guelph in Ontario, numerous public and private
                                                                                                                                                       Canada, and later went on to     research grants
                                                                                                                                                       obtain an additional M.S. in
                                                                                                                                                       Regulatory Affairs from San
                                                                                                                                                       Diego State University.

     Capricor Therapeutics, Inc.     Developing Transformative Therapies from Bench to Bedside                                                                                                                43
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