CAP-1002 for Advanced DMD: A New Treatment Option

October 24, 2019 NASDAQ: CAPR Forward-Looking Statements

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 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; 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, 2018 as filed with the Securities and Exchange Commission on March 29, 2019, and as amended by its Amendment No. 1 to Annual Report on Form 10-K/A filed with the Securities and Exchange Commission on April 1, 2019, in its Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2019, as filed with the Securities and Exchange Commission on August 8, 2019, and in its Registration Statement on Form S-3 as filed with the Securities and Exchange Commission on October 24, 2018, and as amended by its Amendment No. 1 to Form S-3 filed with the Securities and Exchange Commission on July 17, 2019, together with prospectus supplements thereto. 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. CAP-2003 has not yet been approved for clinical investigation.

2 Call Participants

‒ Craig McDonald, M.D., is professor and chair of the Department of Physical Medicine and Rehabilitation and Director of the Clinics at the University of California, Davis. Dr. McDonald is an internationally recognized expert in the clinical management and rehabilitation of neuromuscular diseases including DMD. He is the national PI of the Capricor HOPE-2 Trial.

‒ Linda Marbán, Ph.D. – Chief Executive Officer, Capricor Therapeutics, Inc.

‒ AJ Bergmann, Chief Financial Officer, Capricor Therapeutics, Inc.

3 Dystrophin Deficient Muscular Dystrophy: Diagnosis, Natural History and Current Therapies Craig McDonald, MD Professor and Chair of PM&R Professor of Pediatrics Study Chair CINRG Duchenne Natural History Study University of California Davis Health Sacramento, CA

4 Disclosures

‣ Consulting work on Duchenne muscular dystrophy clinical trials for – Capricor Therapeutics, Inc. – Catabasis Pharmaceuticals, Inc. – PTC Therapeutics – Sarepta – Prosensa – GSK – Pfizer – Eli Lilly – Bristol Myers Squib – Italfarmaco – Mitobridge – Cardero Therapeutics

5 Duchenne Muscular Dystrophy

. The most common muscular dystrophy of childhood . 1 in 3500-5500 boys . BMD is about 1 in 18000-35000

. X-linked recessive inheritance (Xp21.2) . males affected & females carriers . However, 1/3 cases are de novo mutation

. Caused by mutation of dystrophin gene

. Dystrophin gene is the largest gene in genome: 2.4 mb . 14 kb mRNA coding sequence . 3685 amino acid 427kDa protein 6 Duchenne Muscular Dystrophy Is a Devastating Progressive Disease with Significant Unmet Need

‣ Rare recessive x-linked disorder caused by mutation in the DMD gene ‣ Leads to dystrophin deficiency in muscle tissue and subsequently chronic activation of NF-kB ‣ Progressive disease that leads to devastating deteriorating muscle strength and early death ‣ Only supportive treatments are available – Physical therapy – Orthopedic Surgery for contractures and scoliosis – Assisted ventilation – Heart failure management (e.g., afterload reduction) – Off-label / labeled use of corticosteroids – Eteplirsen in the US for exon-51 mutations – Ataluren in the EU for nonsense mutations

7 Disease Progression Is Characterized by Muscle Damage and Replacement of Muscle Fibers with Fat Infiltration and Sclerosis, Resulting in Loss of Function

Lack of dystrophin cause shearing of the sarcolemma and activation of NF-kB, increasing cellular damage and muscle fiber Fat infiltration, sclerotic loss changes and loss of muscle fibers

Progressive loss of muscle fibers and replacement of functional muscle units by fat infiltration and sclerosis

Loss of function; walking capacity preserved in spite of significant loss of Normal muscle tissue muscle strength due to Muscle tissue 19 year old ‣ Reserve capacity in muscle function DMD patient Post-Mortem ‣ Biomechanical compensations

8 Pathophysiology of DMD

Gene abnormality at Xp21 loci ↓ Absence of dystrophin ↓ Muscle membrane injury ↓ Cascade of events leading to muscle fiber injury and degradation ↓ Cycles of degeneration ←→ regeneration ↓ Cell death (replacement by fat & connective tissue)

9 DMD pathomechanism

Structural defect

Membrane instability

Apoptosis / Necrosis

Inflammation

Fibrosis Fiber Death Adapted from Engvall & Wewer (2003) FASEB 17:1579

10 Dystrophin Gene & Protein

From: physrev.physiology.org

• 8 different promoters • Differential tissue expression of dystrophin isoforms • 79 exons (0.6% of gene) and most of the gene composed of non-coding introns

• Dystrophin protein organization: • N-terminal actin binding domain • 24 spectrin like repeats in the rod domain • Cysteine rich and c-terminal • Dystrophin is an important component of DAG complex at muscle membrane • Muscle membrane stability 11 • Cell signalling pathway Duchenne dystrophy = Absence of dystrophin Complete loss of function

Becker dystrophy = Present, but abnormal Partial loss of function

Large in-frame deletions Can be clinically very mild, asymptomatic BMD 12 (hyperCKemia) Types of mutations in Dystrophinopathies

. Deletions account for majority of mutations ~65-72% of DMD ~85 % of BMD most in “hotspot” region of exon 45-53

. Point mutations and splicing region mutations ~25-30% most result in nonsense/frameshift (stop); rare missense

. Duplications ~5-10% in minor “hotspot” region of exon 2-20

. Premature stop codon mutation ~13-15% 13 Reading Frame Rule

Out-of-frame mutations result in disruption of ORF → premature stop codon → truncated dystrophin/non-functional protein → Absence of dystrophin → DMD

In-frame mutations that preserve the ORF → replacements of amino acids in dystrophin → partially functional protein → BMD

Majority of DMD and BMD follow this rule 14 Deletions that disrupt the codon reading frame produce severe Duchenne dystrophy

DP427 muscle, neurons 1 2 3 4 5 6 7 8 9 10 11 12 13 14

15 16 17 18 19 20 21 22 23 24 25 26 DP260 retina 27 28 29 30 31 32 33 34 35 36 37 38

DP140 neurons, kidney 39 40 41 42 43 44 45 46 47 48 49 50

DP116 Schwann cells 51 52 53 54 55 56 57 58 59 60 61

DP71 - 45 universal 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76

77 78 79

15 Deletions that do not disrupt the codon reading frame produce mild Becker dystrophy

DP427 muscle, neurons 1 2 3 4 5 6 7 8 9 10 11 12 13 14

15 16 17 18 19 20 21 22 23 24 25 26 DP260 retina 27 28 29 30 31 32 33 34 35 36 37 38

DP140 neurons, kidney 39 40 41 42 43 44 45 46 47 48 49 50

DP116 Schwann cells 51 52 53 54 55 56 57 58 59 60 61

DP71 - 45 universal 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76

77 78 79

16 DMD ↔ outlier DMD ↔ BMD

Absent/nonfunctional dystrophin protein severe phenotype: DMD

Smaller/partially functional/reduced amount of dystrophin mild phenotype: BMD

. Mutations can result in phenotype within the spectrum . Genotype (mutation characterization)/phenotype correlation is not perfect nor easy . Clinical picture is better at predicting prognosis and disease progression; and immunochemical analysis of dystrophin rarely necessary 17 DMD vs. BMD • Immunostaining using Antibodies to different dystrophin epitopes

• Antibody to C-terminus: • Absent staining: DMD • Present staining: BMD

Antibody to Rod domain may be positive in DMD

• Western Blot Analysis (using C-terminal): • < 2-3% quantity → Duchenne phenotype • 5 – 20% quantity → “Outlier” phenotype • 20 –80% quantity → Becker phenotype • or 90 – 100% & 18 abnormal structure/size from Novocastra DMD vs. BMD Duchenne Becker

Clinical Onset 2 – 6 years 4 – 12 (or later)

Age to wheelchair 7-13 years (no steroids) > 16 years (-) steroids 10 years (often in 3rd (+) steroids 13.5 years decade) Restrictive Lung Progresses to severe Mild severity RLD Disease RLD (2nd decade) Cardiomyopathy Severe Severe (mid to late 2nd (in 3rd to 4th decade) decade) Scoliosis Severe in 80-90% Rare

Life Expectancy 17 – 25 (non-vent) 4th to 6th decade 19 30’s (vent) Interventions that have impacted the natural history of disease progression and survival in DMD

1. Glucocorticoids (GC, still off-label in EU despite proven efficacy) 2. Management of spine deformity a) Glucocorticoids b) Timely spine surgery for curves >30–40 degrees 3. Respiratory management a) Airway clearance strategies / Mech. cough assistance b) Non-invasive ventilation 4. Cardiac management a) Early afterload reduction (e.g. ACE inhibitors) b) Recognition and management of heart failure 5. Novel disease-modifying therapies 20 Stages of DMD are captured with the use of multiple clinical endpoints Example AGE Stages of DMD Disease Clinical 0 Years 5 10 15 20 25 30 Progression Endpoints

Impaired ability to Bayley Delayed & Impaired Acquisition Hop Run Jump NSAA Rise from Floor of Milestones / Motor Skills Loss of TFTs______Rise from Floor Early Ambulatory Stage NSAA (Modest functional decline) TFTs Loss of 6MWT Stair Climb 100 m. QMT Loss of Late Ambulatory Stage NSAA Ambulation (Rapid Functional decline) TFTs. 6MWT. PUL Loss of Upper 100 m. PFTs QMT Limb Early Non-Ambulatory Stage Overhead reach PFTs Loss of Upper Limb Loss of Upper Limb PUL Hand to Mouth Distal Hand EK Scale. QMT

Non-invasive Ventilation (Nocturnal) Late Non-Ambulatory Stage PFTs PUL Non-invasive Ventilation EK Scale (Diurnal)

Death

21 Stages of DMD are captured with the use of multiple clinical endpoints Example AGE Stages of DMD Disease Clinical 0 Years 5 10 15 20 25 30 Progression Endpoints

Impaired ability to Bayley Delayed & Impaired Acquisition Hop Run Jump NSAA Rise from Floor of Milestones / Motor Skills TFTs______

22 Motor and Cognitive Assessment of Infants and Young Boys with Duchenne Muscular Dystrophy: Results from the Muscular Dystrophy Association DMD Clinical Research Network. Connolly et al. (n=25; 1.8±0.8 years)

23 24 NSAA Latent Class Trajectory (UK NSAA) (Muntoni et al.

25 Maturation, stability, and decline on hop and jump

• Maturation phase is similar across cluster classes • Proportion of patients who can hop and jump is highest in patients with milder trajectories 26 • Decline phrase is separated by cluster class Muntoni et al. submitted Performance on rise from floor and run NSAA items by latent trajectory class

Proportion of patients with NSAA item score > 0

A

27 NSAA Score at 30 mean 3 Mean of individual peak 0 2 patient fitted curves with 7 Upper higher and lower 2 quartile quartiles 3 20 Muntoni et al, WMS, 2018 Signorovitch et al, ISPOR, 2018 Lower Score NSAA NSAA quartile 50% of mean peak NSAA 10

Age at mean peak NSAA score 5.9 6. 7.8 8 6 8 10 12 14 16 28 AGE (years) Stages of DMD are captured with the use of multiple clinical endpoints Example AGE Stages of DMD Disease Clinical 0 Years 5 10 15 20 25 30 Progression Endpoints

______Loss of NSAA Rise from Floor Early Ambulatory Stage TFTs (Modest functional decline) 6MWT Loss of 100 m. QMT Stair Climb NSAA Loss of Late Ambulatory Stage TFTs. Ambulation (Rapid Functional decline) 6MWT. PUL 100 m. PFTs QMT

29 CINRG Data: Loss of Ambulation (all mutation subtypes and steroid use, N = 309)

Kaplan-Meier survival estimates 1.00 > 1 year steroids:

0.75 • Median LOA = 13.3 ± 0.3 yrs • 95% CI = 12.5 – 14 yrs 0.50 < 1 month steroids: 0.25 • Median LOA = 9.8 ± 0.2 yrs • 95% CI = 9.3-10.1 yrs

0.00 • (n=309) 0 5 10 15 20 Age (years)

<30 days cumulative GC exp 1 year or greater cumulative GC exposure 30 There Has Been a Changing Natural History in DMD Over the Last 4 Decades Affecting Survival 1960s 1970-1990 No Treatment Spine Surgery & Ventilation

Passamano, et al. Acta Myol. 2012;31(2):121-125. Eagle, et al. Neuromuscul Disord. 2007;17(6):470-475. 31 DMD Survival Affected Primarily by Ventilation

Rall and Grimm: Acta Myol. 2012 Oct;31(2):117-20. Passamano, et al. Acta Myol. 2012;31(2):121-125. • Ventilation was recognized as a main • Ventilation was recognized as a main intervention affecting survival intervention affecting survival

• Ventilated median survival = 27.0 yr • Ventilated mean survival = 27.9 yr (range, 23 - 38.6 yr)

• Without ventilation = 19.0 yr • Without ventilation = 17.7 yr 32 (range, 11.6-27.5 yr) There Has Been a Changing Natural History in DMD Over the Last 4 Decades Affecting Survival 2000 – Present 1980s – Present Glucocorticoids/Steroids Afterload Reduction With ACE Inhibitors

Schram, et al. J Am Coll Cardiol. 2013;61(9):948-954. Duboc D, et al. Am Heart J. 2007;154(3):596-602. 33 Glucocorticoids target NF-κB which is Chronically Activated in DMD

• miRNAs in muscle microenvironments cause variable dystrophin in muscular dystrophy • miRNAs are elevated in dystrophic myofibers and increase with disease severity • Inflammatory cytokines induce miRNAs, and antiinflammatories block their expression • miRNAs provide a precision medicine target in dystrophy and exon skipping

34 35 8 Milestones that are clinically meaningful in DMD (based on PODCI Transfer / Basic Mobility)

Stand Stand Stand Lost Non-Amb Lost Full Lost Hand Lost Lost from from from 4-Stair Full Overhead to Mouth Hand supine supine supine > Climb Overhead Reach (Retains Function < 5 sec 5-10 sec 10 sec or reach (Retains Hand (Brooke 6) Lost Rise Still Amb hand to Function) 36 from Floor mouth) 37 38 39 Stages of DMD are captured with the use of multiple clinical endpoints Example AGE Stages of DMD Disease Clinical 0 Years 5 10 15 20 25 30 Progression Endpoints

Loss of Upper Limb Overhead reach Early Non-Ambulatory Stage

Loss of Upper Limb Loss of Upper Limb PFTs Hand to Mouth Distal Hand PROM PUL EK Scale. QMT Non-invasive Ventilation (Nocturnal) Late Non-Ambulatory Stage PFTs Non-invasive Ventilation PROM PUL (Diurnal) EK Scale Death

40 PPMD Patient and Caregiver Survey

41 Loss of Key Upper Limb Milestones prolonged with steroids by 3-5 years (McDonald et al. Lancet 2018)

42 43 McDonald et al. Lancet, 2018 DMD survival is impacted primarily by ventilation

1.0 Non-ventilated (n = 22) Ventilated (n = 44)

0.8

0.6 Median survival, years (range) Study Ventilated Not ventilated 0.4 Rall & Grimm1 27.0 (20.2-33.8) 19.0 (17.7-20.3) Passamano et al 2 27.9 (23-38.6) 17.7 (22.6-27.5)

Proportion surviving 0.2

0.0 0 5 10 15 20 25 30 35 40 Age (years)

44

1. Rall S, Grimm T. Acta Myol, 2012;31:117-120 2. Passamano L, et al. Acta Myol, 2012;31:121-125 Despite advances in care, respiratory and cardiac complications remain the leading causes of death in DMD

#From the total pool of 340Causes eligible of deathpatients in CINRG (minus-DNHS Indian cohort due to differences50 in standard of care) 32 died over the 8 year study period. Unpublished40 CINRG47% data. n = 32 30 28% 20 25% 10 Percentage of deaths 0 Respiratory Cardiac failure Other failure 45

#From the total pool of 340 eligible patients (minus Indian cohort due to differences in standard of care) 32 died over the 8 year study period. Unpublished CINRG data. Changes in ambulatory milestones correlate to severity of respiratory function decline

FVC%p 80% Start of respiratory function decline1 Loss of ambulation1 = Lower limit of normal1-4 Loss of overhead reach1,8# FVC%p Insufficient cough 50% FVC%p Moderate respiratory insufficiency1,5,6 Loss of self-feeding1,8# 40% FVC%p 30% Severe respiratory Complete loss of 1,5,6 1,8# Respiratory function decline (FVC%p)1 Insufficiency hand function

Respiratory clinical milestone

Lower limb clinical milestone

Upper limb clinical milestone 46

#Brooke score of upper limb function = 3, 5 and 6, respectively.6 %p: percent predicted; FVC: forced vital capacity. 1. Mayer OH, et al. US 2017;13:35–41; 2. Finder JD, et al. Am J Respir Crit Care Med 2017;196:512-9; 3. Finder JD, et al. Am J Respir Crit Care Med 2004;170:456-65; 4. Johnson JD and Theurer WM. Am Fam Physician 2014;89:359-66; 5. Humbertclaude V, et al. Eur J Paediatr Neurol 2012;16:149-60; 6. Mayer OH, et al. J Neuromuscul Dis 2017;4:189- 98; 7. Bushby K, et al. Lancet Neurol 2010;9:177-89; 8. Brooke MH, et al. Neurology 1989;39475-481. Clinical thresholds of respiratory function can guide patient management

Change in PEF%p and FVC%p with age FVC%p 100 PEF%p

80 Raised volume Rx in-exsufflator Daily in-exsufflator / airway 60 clearance 50 Night time ventilation

40 Mouthpiece ventilation 30

Respiratory function test function Respiratory Continuous ventilation n = 334 0 5 10 15 20 25 30 Age (years)

For every 10% reduction in FVC, odds of hypoventilation increase by 20%

1. Mayer OH et al. US Neurology 2017;13:35-41; 2. Bushby K, et al. Lancet Neurol 2010;9:177-89; 3. Birnkrant DJ, et al. Lancet Neurol 2018;17:347-61. 4. Sawnani, H. et al. J Pediatr 2015;166:640-5. 47 Progressive muscle weakness in DMD leads to a sequential loss of function

Upper extremity Respiratory Lower extremity

Respiratory muscle weakness Overhead motion Low lung volumes No overhead Loss of motion ambulation Poor airway clearance Hand to mouth Nocturnal hypoventilation No hand to mouth Diurnal hypoventilation

• 1. Mayer OH, et al. US Neurology 2017;13:35–41; 2. Finder JD, et al. Am J Respir Crit Care Med;Article in Press 2017; 3. Finder JD, et al. Am J Respir Crit Care Med 2004;170:456-65; 4. Johnson JD and Theurer WM. Am Fam Physician 2014;89:359-66; 5. Humbertclaude V, et al. Eur J Paediatr Neurol 2012;16:149-60; 6. Mayer OH, et al. J Neuromuscul Dis 2017;4:189-98; 7. Bushby K, et al. Lancet Neurol 2010;9:177-89; 8. McDonald CM, et al. Neuromuscular Disorders 2016;26:473-80; 9. Brooke MH, et al. Neurology 1989;39475-481. 48 Clinical management of respiratory function decline in DMD

Respiratory muscle weakness

Low lung volumes

Poor airway clearance

Nocturnal hypoventilation

Diurnal hypoventilation

49

• Mayer OH, et al. US Neurology 2017;13:35–41. Clinical management of respiratory function decline in DMD

Respiratory muscle weakness

Hyperinsufflation Rx Low lung volumes Cough assist / Airway clearance Poor airway clearance

Nocturnal hypoventilation

Diurnal hypoventilation

50

• 1. Mayer OH, et al. US Neurology 2017;13:35–41; 2. Birnkrant DJ, et al. Lancet Neurol 2018;17:347-61. Clinical management of respiratory function decline in DMD

Respiratory muscle weakness

Hyperinsufflation Rx Low lung volumes Cough assist / Airway clearance Poor airway clearance Nasal non-invasive ventilation Nocturnal hypoventilation Mouthpiece “Sip” ventilation Diurnal hypoventilation

51

• 1. Mayer OH, et al. US Neurology 2017;13:35–41; 2. Birnkrant DJ, et al. Lancet Neurol 2018;17:347-61. Key Learnings from Natural History in DMD

There is linkage of the timing of functional deterioration and loss of milestones with later disease course in DMD

52 Age at loss of ambulation is linked to age at loss of hand to mouth function

53 Age at Loss of Ambulation Predicts Age at Onset of 1 liter FVC (CINRG Data)

1.00 FVC < 1 liter increases 0.75 risk of death HR 4.1 Proportion 0.50 (95% CI) (1.3, 13.1) Reaching FVC of 1L

0.25 LOA 13 years or still walking LOA <10 years 0.00 0 10 20 30 Age (years) Number at Risk LOA <10 years 53 53 46 22 3 1 0 0 LOA 13 years or still walking 208 208 132 71 27 7 0 0 54 Ambulatory patients age 9-18 at study entry McDonald et al. Lancet, 2018 Median Absolute FVC (Liters) by Age and GC use. Peak in median FVC is shown and the point at which the median absolute FVC value drops below 1 liter.

55 McDonald et al. Neuromuscular Disorders, 2018 Steroid use and all-cause mortality in DMD

• Forty-five deaths occurred over almost 10 years of follow-up

• The odds ratio for death for those on GC treatment ≥ 1 year showed a reduced death risk by over 50%

• (odds ratio 0.47, 95% CI 0.22-1.00, p = 0.05).

56 McDonald et al. Lancet, 2018 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 up hands to mouth standardized arms to shoulder arms reach without a coin or but cannot raise a plastic cup with height simultaneously compensation drive a powered cup with a 200g 200g weight in it to simultaneously w/ above head only Chair weight in it to mouth using both or w/o by flexing the mouth hands if necessary compensation elbow

57 Primary Efficacy Endpoint: PrimaryPerformance Efficacy of Endpoint:the Upper PULLimb Assessment (PUL: v1.2) to to Assess 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 al, 2019; Pane et al, 2018 58 Static positioning leads to contractures in DMD

59 Scoliosis in DMD

Without steroids 80-90% require fusion

With steroids 20-30% require fusion

60 Cardiomyopathy in DMD

• Clinically significant cardiomyopathy rare before age 10; MRI changes common • Fibrosis posterior wall left ventricle • Myocardium exhibits abnormal contractility • Arrythmias

• Treatment: Early ACE Inhibitors; Evidence Class Ia • enalapril, lisinopril, perindopril • ARBs (Losartan) • Beta Blockers (metoprolol, carvedilol) • Aldosterone receptor antagonists (Spironolactone, eplerenone) • Diuretics (Furosemide, Thiazides)

61 Potential for Combination Treatments in DMDDevelopment of State-of-the-Art Combination Therapies for Duchenne Muscular Dystrophy

Replacement ‣ Six main categories for therapeutic of dystrophin/ targets for DMD utrophin Increasing Mitochondria muscle mass ‣ One addresses primary genetic dysfunction and defect; rest address downstream regeneration DMD aspects of the pathogenesis Therapeutic Development Correcting ‣ Targeting any single pathway may Decreasing perturbations be an approvable mono-therapy inflammation in Calcium and fibrosis handling Correcting ‣ Future treatment paradigm may blood flow involve targeting multiple pathways regulation to have greater patient impact

62 Potential for Combination Treatments in DMD ‣ NF-κB Is Chronically Activated in DMD ‣ Prednisone / Prednisolone Replacement of dystrophin/ ‣ Deflazacort (Emflaza, PTC) utrophin Increasing Mitochondria muscle mass dysfunction and ‣ Current Trials: regeneration DMD ‣ Vamorolone (ReveraGen) Therapeutic – Dissociative steroids (decreased Aes) Development Correcting Decreasing ‣ Edasalonexent (Catabasis) perturbations inflammation – covalently linked salicylic acid (ASA) and in Calcium and fibrosis docosahexaenoic acid (DHA), handling Correcting – synergistically leverages the ability of both blood flow compounds to intracellularly inhibit activated regulation NF-κB ‣ Givinostat (Italfarmaco) ‣ ? CAP 1002 63 Potential for Combination Treatments in DMD ‣ Therapeutics targeting dystrophin restoration Replacement of dystrophin/ ‣ Antisense Oligonucleotides utrophin Increasing PMOs Mitochondria muscle mass ‣ dysfunction and regeneration ‣ PPMOs DMD Therapeutic AAV microdystrophin gene Development ‣ Correcting Decreasing perturbations therapy inflammation in Calcium and fibrosis handling Correcting blood flow regulation

64 Potential for Combination Treatments in DMDDevelopment of State-of-the-Art Combination Therapies for Duchenne Muscular Dystrophy

Replacement of dystrophin/ ‣ Myostatin Inhibitors utrophin Increasing Mitochondria muscle mass Investigational dysfunction and ‣ regeneration DMD Therapeutic ‣ Pfizer (IV Q month) Development Correcting Decreasing perturbations inflammation in Calcium and fibrosis ‣ Roche (SQ Q week) handling Correcting blood flow regulation

65 Potential for Combination Treatments in DMD ‣ Therapeutics targeting mitochondrial health Replacement of dystrophin/ ‣ Idebenone (Santhera) utrophin Increasing PPAR agonist (Astellas) Mitochondria muscle mass ‣ dysfunction and regeneration ‣ (+)-epicatechin (Cardero) DMD 𝛅𝛅 Therapeutic Development Correcting Decreasing perturbations inflammation ‣ ? CAP-1002 in Calcium and fibrosis handling Correcting blood flow regulation

66 Acknowledgments

UC Davis Neuromuscular Medicine & Rehabilitation Research Center and CINRG Network

67 Linda Marbán, Ph.D. Capricor CEO

68 Treatment Options for DMD are Limited

Challenges . . EXONDYS 51 –13% of Exon Skipping DMD population . Immunomodulatory . Gene therapy . Gene therapy . Anti-fibrotic . Utrophin . Steroids have adverse side-effects . Pro-regenerative . NF-kB . NF-kB inhibition may . Cellular Energy . Steroids not be enough

We believe CAP-1002 may be used synergistically with other therapeutics aimed to treat DMD

69 Capricor’s Regulatory Designations - DMD

. Goal: to facilitate efficient development and expedite review of a drug Rare Pediatric Disease . Similar to breakthrough therapy designation: Designation . RMAT provides benefits that include more frequent meetings with FDA to discuss the development plan for the product candidate RMAT . eligibility for rolling review and priority review . Products may also be eligible for accelerated Designation approval . on the basis of a surrogate or intermediate endpoint reasonably likely to predict long-term Orphan Drug clinical benefit Designation . reliance upon data obtained from a meaningful number of sites

70 December 2018 RMAT Meeting Summary

. Interdisciplinary meeting with FDA (CBER)

. FDA suggested using PUL v2.0 as primary efficacy endpoint – Interim analysis was positive for PUL 2.0

. FDA stated that the trial would need to show: – Evidence of clinically meaningful changes in the PUL – Stabilization or improvement in other measures of skeletal, respiratory and/or cardiac function . Interim analysis for HOPE-2 shows all of these improving in treated patients over placebo

. FDA advised CAPR to request an end of phase meeting after completion of the trial to determine whether HOPE-2 could serve as the registration study. – Discussions with FDA are ongoing regarding CAP-1002 and DMD

71 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 proteins  Internalized by target cells  Stimulate diverse and lasting changes in cellular behavior  3 known miRNAs drive CAP-1002 potency

. CAP-1002 has been investigated in multiple independent clinical trials and more than 150 human subjects

72 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 Biotech focused on chemistry, manufacturing and controls (CMC)

73 HOPE-2 Clinical Trial 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 every 3 months . Delivery: Intravenous infusion . Sites: approximately 9 sites (USA)

https://www.clinicaltrials.gov/ct2/show/study/NCT03406780 74 HOPE-2 Interim Analysis Safety Results

. A total of 57 infusions were performed in HOPE-2 as of July 31, 2019 . With the exception of two serious adverse events1,2 in the form of immediate allergic reactions, no safety signals were identified . To reduce the risk of future adverse events, Capricor initiated a commonly used pre-medication regimen including oral steroids and antihistamines . Since initiation of the pre-treatment regimen, approximately 40 infusions of CAP-1002 or placebo have been administered with only one serious adverse event1 reported that required an overnight observation of the patient.

1Assessed as related to either CAP-1002 or placebo administration 2One SAE each in HOPE-2 and HOPE-OLE 75 HOPE-2 Interim Analysis Data Summary

. Skeletal: . Mid-Level PUL 2.0 at 6 months (p=0.0612) . Shoulder + Mid + Distal Level PUL 2.0 at 6 months (p=0.0299) and strong signal at 3 months (p=0.0549) . Mid + Distal Level PUL 2.0 at 6 months (p=0.0177) . Tip to Tip strength (independent skeletal measure) at 6 months (p=0.0111) . Respiratory . Trends towards improvements in PEF (% predicted) and IFR (absolute) . Cardiac . Improvements in wall thickening (similar to positive changes seen in HOPE-Duchenne) . LV myocardium mass

76 Improvements in PUL 2.0 Observed Mid + Distal

‒ Δ 1.6 difference in CAP-1002 vs. placebo at 6-months p= 0.0177 ‒ Skeletal muscle function

improved in non-ambulant n=8 n=6 patients with DMD n=10 ‒ Could help patients maintain n=8 independence if function is improved or decline attenuated

Comparisons treated vs. placebo using mixed model repeated measures ANOVA with covariates Analysis done in Sept. ITT Population Colored boxes heights, either positive or negative, represent mean change from baseline Bars represent ± one standard deviation from the mean P-values are nominal without adjustment for multiple testing or claims of statistical significance

77 Conclusions and Future Directions

Conclusions: Moving Forward:

. First placebo-controlled trial . Meet with FDA to determine if in DMD to use PUL 2.0 for CAP-1002 potentially qualifies for evaluation of efficacy accelerated approval based on . First placebo-controlled trial RMAT standards showing upper limb – Based on Guidance for functional improvements in Industry: Expedited Programs non-ambulant DMD for Regenerative Medicine patients Therapies for Serious . Directionally consistent Conditions improvements in function, strength, pulmonary and cardiac endpoints

78 Duchenne Market Statistics and 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 = $600,000

Revenue Projections* . Est. Annual Revenue (10% market penetration): $450M . Est. Annual Revenue (50% market penetration): $2.25B

*Based on internal projections and estimates 79 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 Children's Hospital (USA)

John Jefferies, M.D. Cincinnati Children's Hospital Medical Center (USA)

Oscar Henry Mayer, M.D. Children's Hospital of Philadelphia (USA)

Eugenio Mercuri, M.D., Ph.D. Catholic University of the Sacred Heart (Italy)

Francesco Muntoni, M.D. University College London (UK)

Thomas Voit, M.D. University College London (UK)

Lee Sweeney, Ph.D. University of Florida (USA)

Michael Taylor, M.D., Ph.D. Cincinnati Children's Hospital Medical Center (USA)

80 Thank you

Questions and Answer

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