A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but...

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NASDAQ: CAPR A Translational Medicine Company www.capricor.com Corporate Presentation July 2016

Transcript of A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but...

Page 1: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

NASDAQ: CAPR

A Translational Medicine Company

www.capricor.com

Corporate PresentationJuly 2016

Page 2: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

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This presentation contains forward-looking statements and information that are based on the beliefs of themanagement of Capricor Therapeutics, Inc. (Capricor) as well as assumptions made by and informationcurrently available to Capricor. All statements other than statements of historical fact included in thispresentation are forward-looking statements, including but not limited to statements identified by the words“anticipates,” “believes,” “estimates,” and “expects” and similar expressions. Such forward-lookingstatements also include any expectation of or dates for commencement of clinical trials, IND filings, similarplans or projections and other matters that do not relate strictly to historical facts. These statements reflectCapricor’s current views with respect to future events, based on what we believe are reasonableassumptions; however, the statements are subject to a number of risks, uncertainties andassumptions. There are a number of important factors that could cause actual results or events to differmaterially from those indicated by such forward-looking statements. More information about these and otherrisks that may impact Capricor's business are set forth in Capricor's Annual Report on Form 10-K for theyear ended December 31, 2015, as filed with the Securities and Exchange Commission on March 30, 2016,and in its Registration Statement on Form S-3, as filed with the Securities and Exchange Commission onSeptember 28, 2015 and in our Quarterly Report on Form 10-Q for the period ending March 31, 2016 asfiled with the Securities and Exchange Commission on May 13, 2016. Should one or more of these risks oruncertainties materialize, or should underlying assumptions prove incorrect, actual results may varymaterially from those in the forward-looking statements. Further, Capricor’s management does not intendto update these forward-looking statements and information after the date of this presentation.

Forward-Looking Statements

Page 3: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

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– Capricor harnesses the heart’s intrinsic regenerative machinery,which normally serves to offset the low rate of ‘wear-and-tear’ cellular loss

– Capricor science has been reported in >100 peer-reviewed publications,and has been a subject of >25 independent labs around the globe

– Therapeutic concept has been validated by clinical results

– Capricor is led by world-class scientific and executive teams

Capricor: Realizing the Promise of Therapeutic Regeneration

Page 4: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

4Leadership & Key Scientific Advisors

Frank Litvack, MDExecutive Chairman

Partner, Pura Vida InvestmentsFormer CEO, Conor Medsystems

Eduardo Marbán, MD PhDChairman, Scientific Advisory Board & Co-Founder

Director, Heart Institute, Cedars-Sinai Medical CenterFormer Chief of Cardiology, Johns Hopkins University

John Jefferies, MD MPH FAAP FACCCo-Director, Advanced Heart Failure and Cardiomyopathy

Cincinnati Children’s Hospital Medical CenterAssociate Professor, U. of Cincinnati Dep’t of Pediatrics

Jeff Karp, PhDAssociate Professor, Harvard Medical School

Principal Faculty at the Harvard Stem Cell InstituteMIT Technology Review - Top Innovator Under 35

David Sachs, MDRussell Professor of Surgery and Immunology,

Harvard Medical School and Director,Transplantation Biology Research Center, MGH

Timothy Henry, MDDirector, Division of Cardiology

Heart InstituteCedars-Sinai Medical Center

Raj Makkar, MDDirector, Interventional CardiologyAssociate Director, Heart Institute,

Cedars-Sinai Medical Center

Linda Marbán, PhDChief Executive Officer

Co-FounderLeland Gershell, MD PhDChief Financial Officer

Deborah Ascheim, MDChief Medical Officer

Page 5: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

5Capricor Investment Highlights

We are a clinical-stage regenerative medicine company developingtherapeutic products based on an allogeneic cell platform.

CAP-1002 (cardiac cell therapy) – in two Phase 2 programs

Duchenne heart disease – the leading cause of death in DMDTop-line results of HOPE trial expected in Q1 2017

Adult heart disease – the leading cause of death globallyDYNAMIC trial results illustrate benefit in sick populationExpect decision on Janssen Biotech license option following ALLSTAR trial results in H1 2017

CAP-2003 (cardiac exosomes) – cell-free, ‘next-gen’ technology to enter clinic in 2017

Secreted by CAP-1002 and are potent mediators of its biological actions

Page 6: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

6Regenerative Medicine for the Heart to Date

(hours~days) (days~weeks) (weeks~months)Heart Attack Infarct Expansion Chronic LV DilationThinning

Heart Failure

“adverse remodelling”

Therapeutic strategies aimed to correct the underlying disease in heart failure:– Have shown inconsistent functional benefit– Have shown no evidence of therapeutic regeneration, such as:

Reduction of scarGrowth of new cardiac tissueImprovement of function

Page 7: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

7Clinical Validation Provided by the CADUCEUS Trial

Lancet, 2012, 21(6): 1121-1135.

Showed for the first time that heart regeneration is therapeutically possibleProvides hope for a curative approach vs. stabilization, palliation

– Randomized trial in 25 patients with reduced ejection fraction following heart attack– One-time intracoronary delivery of 25M autologous cardiosphere-derived cells (CDCs)– Sponsored by Cedars-Sinai Medical Center, with Johns Hopkins University

Page 8: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

8Heart Cells for Heart Disease

Capricor’s core technology is the cardiosphere-derived cell (CDC):– Does not act by ‘stemness’ – does not engraft into myocardium– Exerts favorable and durable effects on target cells via exosome signalling

– cardiomyogenic, anti-apoptotic, angiogenic, anti-fibrotic

CAP-1002 (allogeneic CDCs) is an “off the shelf” product– One donor heart can provide thousands of doses of CAP-1002– Product is packaged in Cryostor™, has 3-year frozen shelf life– Clinical material currently produced at Capricor facility via proprietary process– Commercial-scale process development in collaboration with Janssen

Record of immunological safety per cumulative clinical experience

IP licensed from Cedars-Sinai Medical Center, Johns Hopkins, U. of Rome

Page 9: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

9Manufacturing Overview

Page 10: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

10Pipeline Summary

Product Candidate Indication Preclinical Phase 1/2 Phase 2 Phase 3 Development Plans

CAP-1002

Duchenne Muscular Dystrophy

To complete HOPE enrollment in Q3:16 To report top-line HOPE results in Q1:17

Advanced Heart Failure

To present 12-month DYNAMIC results at scientific conference

Post Myocardial Infarction

Expect decision on Janssen license option in H1:17

CAP-2003 TBA To initiate clinical development in 2017

Cenderitide Heart Failure Potential out-license opportunity

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– CADUCEUS data attracted the interest of big pharma

– Capricor granted Janssen Biotech an exclusive option to enter into exclusive license agreement for worldwide rights to CAP-1002 for certain CV indications

– Expect decision on license option in H1:17

License fee and additional milestone payments totaling up to $325 millionLow double-digit royalties on product sales

– Collaboration with Janssen on manufacturing development since 2014

– Janssen paid $12.5 million upfront

Capricor Technology has been Validated by Janssen

Page 12: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

12Capricor – Portfolio at a Glance

CAP-1002

CAP-2003

NatriureticPeptides

AdultCardiac Conditions

PROGRAM

Phase I / II

Page 13: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

13ALLSTAR Trial Enrollment Anticipated to Complete in Q3:16

– Similar patient population as CADUCEUS yet using allogeneic cells

– Randomized, double-blind, placebo-controlled; 30-35 U.S. centers

– 120 subjects with recent (30 – 90 d) or chronic (91 – 365 d) STEMI or NSTEMILeft ventricular scar size ≥15% of LV massLeft ventricular ejection fraction ≤45%

– 25 million CDCs or saline infused one time into infarct-associated coronary arteryFollowed for 12 months post-dosing

– Efficacy evaluated by centrally-read cardiac MRI and other measures

– Expect decision on Janssen license option in H1:17

Page 14: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

14ALLSTAR Phase I Results:Showed Improvement in Scar Size

* by groups t-test # by paired t-test

– Results shown are from the “Phase II Equivalent” populationReceived high dose CAP-1002Lacked donor-specific antibodies (DSAs)

DSA = donor-specific antibody

p < 0.05 #p < 0.05 *

n=8 n=8 n=7

Infa

rct S

ize

Infa

rct S

ize

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– >5 million U.S. patients estimated to have heart failureHeart disease is the #1 cause of death in the U.S.>$300 billion in direct and indirect annual costs associated with CV disease and stroke

– Current treatments largely fail to address the progressive underlying disease

– In a preclinical model of non-ischemic dilated cardiomyopathy,CDCs were shown to: reverse abnormalities in cell signaling

prevent adverse remodellingimprove survival

– In the recent DYNAMIC trial in patients with advanced heart failure, CAP-1002demonstrated concordant improvements in: functional status

quality-of-lifeleft ventricular function and size

CAP-1002’s Opportunity in Advanced Heart Failure

Page 16: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

16Design of DYNAMIC I Clinical Trial of CAP-1002

– Open-label, dose-escalation clinical trial in heart failure patientsConducted at Cedars-Sinai Medical Center

– Enrollment was open to subjects with dilated cardiomyopathyNYHA Class III or ambulatory Class IVIschemic or non-ischemic origin

– Baseline LV EF <40% by cardiac CT

– One-time triple coronary infusion at one of four doses37.5, 50, 62.5, or 75 million cells

– Six- and 12-month follow-up

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NYHA Class Physical ActivityI No limitation

II Slight limitation

III Marked limitation

IV Severe limitation

* N=14; two subjects lost to follow-up.

6-Month DYNAMIC Results on CAP-1002 For Advanced HF Presented at the American Heart Association Annual Meeting, November 2015*

– Of the 12 evaluable Class III patients at six months,11 (92%) improved by at least one class (p=0.006)

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Left Ventricular Dynamics & Dimensions

less is better

* N=14; two subjects lost to follow-up; measurements assessed by echocardiography; AHA Annual Meeting, November 2015.

6-Month DYNAMIC Results on CAP-1002 For Advanced HF Presented at the American Heart Association Annual Meeting, November 2015*

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1912-Month DYNAMIC Data Indicate Sustained Benefit

Efficacy signal continued to be observed at 12 monthsLVEF +17.5% (median) from baseline (p=0.02)

Page 20: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

20Capricor – Portfolio at a Glance

CAP-1002

CAP-2003

NatriureticPeptides

DuchenneMuscular Dystrophy

PROGRAM

Phase II

Page 21: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

21DMD Cardiomyopathy is #1 Cause of Death in DMD

– DMD results from mutation in dystrophin gene– 1 per 3,500 male births

– Lack of functional dystrophin in heart leads to: inflammationcardiomyocyte deathprogressive cardiac fibrosis

– Hearts become dilated and non-compliant, and eventually fail

– No approved therapies for heart disease associated with DMD

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Menon et al, Pediatr Cardiol 2014;35:1279-85.

Heart Failure is the End Result of Progressive Scarring

Tandon et al, J Am Heart Assoc 2015;4:e001338.

– In DMD, myocardial fibrosis (scar):

– Independently predicts adverse cardiac remodeling, ventricular arrhythmia, death– Increases linearly with age and strongly correlates with LV ejection fraction

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30

40

50

60

70

80

Mdx + CAP-1002Mdx + Vehicle

*** p < 0.001 *p < 0.05

100200300400500600700800

3 4 5 6

CTL

Mdx + CAP-1002

Mdx + vehicle

Week

***

1st injection

EF (%

)

Repeat Dosing

Met

ers

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Mdx mice + CDC, n=12 Mdx mice + vehicle, n=12 CTL (wild-type), n=5

CAP-1002 Improves Cardiac Function andExercise Capacity in DMD Mouse Model

ISEV, April 2015; AHA, November 2014

* *

* *

Page 24: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

24CDCs Restore Mitochondrial Ultrastructure in DMD ModelMdx+Vehicle Mdx+CDCCTL(WT)

A

10

15

20

25

30

35

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45

50

* <0.005920

970

1020

1070

1120

1170

1220

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20

30

40

50

60

70*

MITOCHONDRIAL LENGTHn=350 per group

CRISTAE/MITOn=100 per group

* **

ROUNDED CRISTAEn=100 per group

B

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25CDCs Augment Cardiomyogenesis in DMD Model

00.0010.0020.0030.0040.0050.0060.0070.0080.009

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– Boys with cardiomyopathy secondary to DMD

– N=24, parallel-group study (3-4 sites)1:1 randomization to one-time CAP-1002 (75 million cells)or ‘usual care’

Randomize

Usual Care

M12W2 W6 M3 M630 d

Randomized Phase I / II HOPE-Duchenne Trial Ongoing

Screen

* FDA Draft Guidance, June 2015.

CAP-1002Infusion

– Expect to report six-month top-line data in Q1 2017Structural (cardiac MRI)* and functional endpoints Quality of Life endpoints

Passed interimDSMB safety review

Success in HOPE may enable Capricor to discuss a BLA with FDA by late 2017.

Page 27: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

27Capricor – Portfolio at a Glance

Diseases of Inflammationand Fibrosis

CAP-1002

CAP-2003

NatriureticPeptides

PROGRAM

Preclinical

Page 28: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

28Exosomes: Next-Generation Regenerative Medicine Platform

Camussi et al, Kidney Int 2010;78:838–848.

– Exosomes are extracellular vesicles secreted by CDCs that mediate their regenerative and cardioprotective effects

Discovered in the course of elucidatingCDCs’ mechanism of action

– CDC Exosomes (CAP-2003) represent a potential cell-free regenerative medicine technology

– Capricor has demonstrated evidence of biological effect in several preclinical models:

CardiacDermatologicOphthalmologic

– Exclusive WW license to CDC Exosomes technology from Cedars-Sinai Medical Center

Page 29: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

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ControlCAP-2003(low-dose)

CAP-2003(high-dose)

– Keratoconjunctivitis induced in rabbits (wound followed by LPS application)

– After development of severe inflammation, eyes were treated with a single administration of CAP-2003 or control, then followed for three days

– Day three data show that CAP-2003 can rapidly improve:– corneal wound injury– ocular surface inflammation– conjunctivitis– corneal edema

LPS = lipopolysaccharide

CAP-2003 Provides Rapid and Dose-Dependent Improvement in Ocular Inflammation Model

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Cash, cash equivalents, and marketable securitiesreported at March 31, 2016 $14.3 million

Net cash used in operations in 2015 $10.8 million

Shares outstanding (May 12, 2016) 18.0 million

Cash Runway Through Early 2017 Data Readouts

Page 31: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

31Recent and Upcoming Milestones

CAP-1002 in Duchenne Heart Disease Passed HOPE interim DSMB review in April 2016 Expect to report six-month top-line results of HOPE trial in Q1:17

CAP-1002 in Adult Heart Disease Reported positive 12-month DYNAMIC clinical data in June 2016 Expect Janssen decision on license option in H1:17

CAP-2003 Demonstrated evidence of activity in several pre-clinical disease models Expect to submit IND application for initial clinical indication in H1:17

Page 32: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

NASDAQ: CAPR

A Translational Medicine Company

www.capricor.com

8840 Wilshire Boulevard – 2nd floorBeverly Hills, CA 90211(310) 358-3200

Page 33: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

33Appendix

Page 34: A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but not limited to statementsidentified by the words “anticipates,” “believes,”

34Properties of CDCs

– CD105+/CD45- cells1,2 of intrinsic cardiac origin3

– <25% CD90+ (unlike MSCs)1

– <2% DDR2+/SMA+ (unlike fibroblasts or myofibroblasts)– TnI/TnT/MHC/α-SA- (unlike cardiomyocytes)4

– Shrink scar and increase viable myocardium1,2,4-8

– Functionally superior to other clinically-applied cells5

– Multipotent & clonogenic,4 but long-term engraftment & differentiation not necessary for benefit6-8

– ~20μ diameter (max safe dose i.c. = 350,000 CDCs/kg)9

1. RR Smith et al, Circ 2007; 2. Makkar et al., Lancet 2012; 3. A White et al., EHJ 2011; 4. D Davis PLoS One 2010; 5. T-S Li et al, JACC 2012; 6. I. Chimenti et al, Circ Res 2010; 7. K. Malliaras et al, Circ 2012; 8. K. Malliaras et al., EMBO Mol Med 2012; 9. P Johnston et al, Circ 2010

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Ibrahim et al, Stem Cell Reports 2014;2:606-19.

Effects not observed withexosomes from other cell types

CDC Exosomes Significantly Improve Cardiac Structure and Function in Preclinical Studies

0

5

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CTRL NHDF-XO MSC-XO CDC-XO

Scar

Mas

s (m

g)D

ay 3

0

*****

25

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1 15 30

EF (%

)

Days post MI

ControlCDC-XONHDF-XOMSC-XO * **

Control NHDF-Exosomes

MSC-Exosomes CDC-Exosomes

**p < 0.01*p < 0.05

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36Cenderitide (CD-NP) – For Potential OutlicenseDual Natriuretic Peptide Receptor Activator for Cardio-Renal Disease States

– Provides a first-in-class product licensing opportunityPositioned to address a large heart failuremarket segment lacking in therapeutic options

– Proof-of-concept for chronic patch pump deliveryTwo Phase II PK/PD studies have been completedWell-tolerated at pharmacologically-active levelsFlexible dosing for individual dose titration

– Designed for outpatient management of heart failure

OmniPod®

(Insulet)