A Translational Medicine Company - Capricorpresentation are forward-looking statements,including but...
Transcript of 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 PresentationJuly 2016
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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
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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
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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
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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
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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
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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
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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
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9Manufacturing Overview
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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
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12Capricor – Portfolio at a Glance
CAP-1002
CAP-2003
NatriureticPeptides
AdultCardiac Conditions
PROGRAM
Phase I / II
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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
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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
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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)
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20Capricor – Portfolio at a Glance
CAP-1002
CAP-2003
NatriureticPeptides
DuchenneMuscular Dystrophy
PROGRAM
Phase II
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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
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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
2nd injection
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
* *
* *
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24CDCs Restore Mitochondrial Ultrastructure in DMD ModelMdx+Vehicle Mdx+CDCCTL(WT)
A
10
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* <0.005920
970
1020
1070
1120
1170
1220
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10
20
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40
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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.
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27Capricor – Portfolio at a Glance
Diseases of Inflammationand Fibrosis
CAP-1002
CAP-2003
NatriureticPeptides
PROGRAM
Preclinical
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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
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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
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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
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NASDAQ: CAPR
A Translational Medicine Company
www.capricor.com
8840 Wilshire Boulevard – 2nd floorBeverly Hills, CA 90211(310) 358-3200
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33Appendix
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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
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CTRL NHDF-XO MSC-XO CDC-XO
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ay 3
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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)