Capricor Therapeutics, Inc. · NASDAQ:CAPR

Capricor Therapeutics — Technical Presentation (April 2020)

44 slides from Capricor Therapeutics's technical presentation, Apr 15, 2020

1. Slide 1: Cardiac Complications of Duchenne Muscular Dystrophy

   Key Opinion Leader Call – April 15, 2020 Cardiac Complications of Duchenne Muscular Dystrophy NASDAQ: CAPR Capricor Therapeutics, Inc. Developing Transformative Therapies from Bench to Bedside

2. Slide 2: Forward-Looking Statements

   Forward-Looking Statements Statements in this presentation release regarding the efficacy, safety, and intended utilization of Capricor's product candidates; the initiation, conduct, size, timing and results of discovery efforts and clinical trials; the pace of enrollment of clinical trials; plans r

3. Slide 3: Call Participants

   Call Participants Michael Taylor, M.D., Ph.D. – Director of cardiac MR at Cincinnati Children's Hospital Linda Marban, Ph.D. – Capricor CEO Capricor Therapeutics, Inc. Developing Transformative Therapies from Bench to Bedside 3

4. Slide 4: Duchenne muscular dystrophy and the heart

   Duchenne muscular dystrophy and the heart Michael D. Taylor, MD, PhD Director of cardiac MR 4

5. Slide 5: Duchenne muscular dystrophy and the heart

   Duchenne muscular dystrophy and the heart • Duchenne muscular dystrophy: Overview • Cardiomyopathy of DMD – Heart muscle – Electrical system – Natural history of DMD cardiomyopathy • Current evaluation and treatment paradigm • Novel approaches to cardiac therapy 5

6. Slide 6: Duchenne Muscular Dystrophy

   Duchenne Muscular Dystrophy • Dystrophin mutations • X-linked recessive • Muscle wasting disease • Patchy progressive fibrosis Skeletal myopathy Cardiomyopathy 6

7. Slide 7: Duchenne Muscular Dystrophy

   Duchenne Muscular Dystrophy • Dystrophin mutations • X-linked recessive • Muscle wasting disease • Patchy progressive fibrosis 7

8. Slide 8: Neuromuscular diseases with cardiomyopathy

   Neuromuscular diseases with cardiomyopathy Neuromuscular diseases • Duchenne muscular dystrophy • Becker muscular dystrophy • Other muscular dystrophies – Emery-Dreyfus – Myotonic dystrophy I 8

9. Slide 9: Neuromuscular diseases with cardiomyopathy

   Neuromuscular diseases with cardiomyopathy • Duchenne muscular dystrophy • Becker muscular dystrophy • Other muscular dystrophies – Emery-Dreyfus – Myotonic dystrophy I Circulation. 2017;136(13):e200-e231 9

10. Slide 10: Duchenne cardiomyopathy

    Duchenne cardiomyopathy • Affects 1 in 3500 males. • Caused by dystrophin gene mutations • Results in progressive skeletal muscle weakness. • Results in progressive heart cell death. • By 18, 70% have depressed heart function. Viollet, L. (2012) Am J Cardiol, 110(1), 98-102. 10

11. Slide 11: Multifocal degenerative changes

    “Multifocal degenerative changes” “Fibrosed adipose tissue” 11

12. Slide 12: D'Amario D, Heart. 2017;103(22):1770-1779.

    D'Amario D, Heart. 2017;103(22):1770-1779. 12

13. Slide 13: D'Amario D, Heart. 2017;103(22):1770-1779.

    D'Amario D, Heart. 2017;103(22):1770-1779. 13

14. Slide 14: D'Amario D, Heart. 2017;103(22):1770-1779.

    D'Amario D, Heart. 2017;103(22):1770-1779. 14

15. Slide 15: D'Amario D, Heart. 2017;103(22):1770-1779.

    D'Amario D, Heart. 2017;103(22):1770-1779. 15

16. Slide 16: Survival by era

    Survival by era Neuromuscular Disorders. 2002;12(10):926-929. **SS  spine surgery 16

17. Slide 17: Survival by era

    Survival by era Acta Myol. 2012 Oct; 31(2): 121–125 Neuromuscular Disorders. 2002;12(10):926-929. **SS  spine surgery 17

18. Slide 18: Survival by era

    Survival by era Acta Myol. 2012 Oct; 31(2): 121–125 50% ~27 y Neuromuscular Disorders. 2002;12(10):926-929. **SS  spine surgery Acta Myol. 2012 Oct; 31(2): 117–120 18

19. Slide 19: Created by Chet Villa, MD and Tom Ryan, MD CCHMC Neuromuscular Clinic (2019)

    Created by Chet Villa, MD and Tom Ryan, MD CCHMC Neuromuscular Clinic (2019) 19

20. Slide 20: % significant arrhythmias

    45 40 40 % significant arrhythmias 35 30 25 20 15 10 3 4 5 1 0 Total Normal function Mild - moderate Severe dysfunction dysfunction J Am Heart Assoc. 2015;5(1) 20

21. Slide 21: Why cardiac MR?

    Why cardiac MR ? Cincinnati changing the outcome together

22. Slide 22: Cardiac MR in Duchenne

    Cardiac MR in Duchenne • Replaces echocardiogram after age 6-8 • Patients undergo yearly exams • No sedation • Typical exam ~30 minutes • Abbreviated non-contrast version ~10 minutes • 2238 exams since 2004 22

23. Slide 23: Cardiac MR findings

    Cardiac MR findings Cardiac function – advanced disease Late gadolinium enhancement (“LGE”) 23

24. Slide 24: DMD cardiomyopathy – natural history

    DMD cardiomyopathy – natural history Hor, K. N., et al. (2013). JCMR, 15(1), 107. Neuromuscul Disord. 2018;28(11):910-913. 24

25. Slide 25: DMD cardiomyopathy – natural history

    DMD cardiomyopathy – natural history Normal function Abnormal function Neuromuscul Disord. 2018;28(11):910-913. Cardiac MR Hor, K. N., et al. (2013). JCMR, 15(1), 107. 25

26. Slide 26: Tandon, A., et al. (2015). Journal of the American Heart Association, 4(4),

    Tandon, A., et al. (2015). Journal of the American Heart Association, 4(4), 26

27. Slide 27: Created by Chet Villa, MD and Tom Ryan, MD CCHMC Neuromuscular Clinic (2019)

    Created by Chet Villa, MD and Tom Ryan, MD CCHMC Neuromuscular Clinic (2019) 27

28. Slide 28: Therapies – current evidence

    Therapies – current evidence J Am Coll Cardiol. 2016;67(21):2533-2546. 28

29. Slide 29: Therapies – current evidence

    Therapies – current evidence Steroids Lancet. 2018;391(10119):451-461. doi:10.1016/S0140-6736(17)32160-8. J Am Coll Cardiol. 2016;67(21):2533-2546. 29

30. Slide 30: Therapies – current evidence

    Therapies – current evidence Steroids J Am Coll Cardiol. 2016;67(21):2533-2546. J Am Coll Cardiol. 2013;61(9):948-954. 30

31. Slide 31: Therapies – current evidence

    Therapies – current evidence ACE inhibitors J Am Coll Cardiol. 2016;67(21):2533-2546. Am J Cardiol. 2006;98(6):825-827 31

32. Slide 32: Therapies – current evidence

    Therapies – current evidence Mineralcorticoid receptor antagonists J Am Coll Cardiol. 2016;67(21):2533-2546. Lancet Neurology (2014) 14(2), 1–9. 32

33. Slide 33: Lancet Neurology (2014) 14(2), 1–9.

    Lancet Neurology (2014) 14(2), 1–9. 33

34. Slide 34: 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 • Mechanism: cells secrete exosomes: – Contain miRNA, non-coding RNAs and

35. Slide 35: 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 sca

36. Slide 36: HOPE-Duchenne: Reduced Cardiac Scar and Improved PUL

    HOPE-Duchenne: Reduced Cardiac Scar and Improved PUL Scar INFERIOR IMPROVEMENT WALL 36 Taylor M, Jefferies J, Byrne B, et al. Cardiac and skeletal muscle effects in theR.G. randomized Victor et al.,HOPE-Duchenne trial. AHA LBCT 2017; M. Neurology. Taylor et al., submitted 2019;92(8):e866-e878. *p-va

37. Slide 37: 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)

38. Slide 38: Advanced heart failure therapies

    Advanced heart failure therapies • 2019 study of 43 DMD patients with severe dysfunction • Ventricular assist device – 4 • Heart transplant – 1 Prog Pediatr Cardiol. 2019;53:11-14. 38

39. Slide 39: Therapeutic strategies

    Therapeutic strategies Courtesy of Craig McDonald, MD 39

40. Slide 40: Summary

    Summary • Duchenne associated cardiomyopathy is an inexorably progressive disease with variable onset. • Current therapies provide marginal therapeutic benefit. • These patients need a transformative therapy that prevents the replacement of cardiac muscle cells or provides new muscle cells. 40

41. Slide 41: Thank you

    Thank you Question and Answers info@capricor.com NASDAQ: CAPR 41

42. Slide 42: Cardiac magnetic resonance group

    Cardiac magnetic resonance group Cardiology Michael Taylor, MD, PhD Tarek Alsaied, MD Sean Lang, MD Ryan Moore, MD Justin Tretter, MD Radiology Eric Crotty, MD Rob Fleck, MD Manu Rattan, MD Physics Amol Pednekar, PhD 42 Jean Tkach, PhD

43. Slide 43: LGE – What is it really showing?

    LGE  What is it really showing? • Collagen replacement • Gross fibrosis • Protein infiltration • Myocardial disarray • Fine interstitial fibrosis without disarray Moon, J. C. C., et al. (2004).. JACC, 43(12), 2260–2264. 43

44. Slide 44: Circumferential Strain Analysis in Duchenne Muscular Dystrophy

    Circumferential Strain Analysis Identifies Strata of Cardiomyopathy in Duchenne Muscular Dystrophy A Cardiac Magnetic Resonance Tagging Study Kan N. Hor, MD,* Janaka Wansapura, PHD,f Larry W. Markham, MD,+ Wojciech Mazur, MD,§ Linda H. Cripe, MD,* Robert Fleck, MD,+ D. Woodrow Benson, MD, PHD,* Will

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