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TRANSCRIPT
NASDAQ: CAPR
Transformative Therapies from Bench to Bedside
www.capricor.com
28th Annual ROTH Conference
March 15, 2016
2
Forward-Looking Statements
This presentation contains forward-looking statements and information that are based on the
beliefs of the management of Capricor Therapeutics, Inc. (Capricor) as well as assumptions made
by and information currently available to Capricor. All statements other than statements of
historical fact included in this presentation are forward-looking statements, including but not
limited to statements identified by the words “anticipates,” “believes,” “estimates,” and “expects”
and similar expressions. Such forward-looking statements also include any expectation of or
dates for commencement of clinical trials, IND filings, similar plans or projections and other
matters that do not relate strictly to historical facts. These statements reflect Capricor’s current
views with respect to future events, based on what we believe are reasonable assumptions;
however, the statements are subject to a number of risks, uncertainties and assumptions. 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 are set forth in Capricor's Annual Report on Form 10-K for
the year ended December 31, 2014, as filed with the Securities and Exchange Commission on
March 16, 2015, in its Registration Statement on Form S-3, as filed with the Securities and
Exchange Commission on September 28, 2015, and in its Quarterly Report on Form 10-Q for the
quarter ended September 30, 2015, as filed with the Securities and Exchange Commission on
November 13, 2015. Should one or more of these risks or uncertainties materialize, or should
underlying assumptions prove incorrect, actual results may vary materially from those in the
forward-looking statements. Further, Capricor’s management does not intend to update these
forward-looking statements and information after the date of this presentation.
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Changing the Paradigm
– Focus on cardiovascular indications
– Clinical programs in heart failure, Duchenne’s muscular dystrophy
– Innovative platforms: Regenerative Medicine, Exosomes
– Technology licensed from world-renowned academic institutions
4
Cardiosphere-Derived Cells
Exosomes Platform
Natriuretic Peptide
Capricor’s Platforms & Therapeutic Pipeline
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Cardiosphere-Derived Cells (CDCs)
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CDCs – Regenerative Medicine Platform
Cardiosphere-derived
cells (CDCs)
Cardiospheres
(CSps)
Explant-derived
cells (EDCs) Explants Cardiac Tissue
CDCs Function as a Local Drug Delivery System:
– Prevent cardiomyocyte apoptosis (programmed cell death)
– Promote cardiomyocyte proliferation (cell growth) and
angiogenesis (new blood vessel formation)
– Anti-fibrotic (anti-scarring)
– Attract endogenous stem cells (paracrine)
7
CADUCEUS: Proof-of-Concept Clinical Data
– One-time intracoronary delivery of CAP-1001 = autologous CDCs
– Patients with reduced ejection fraction (EF) following myocardial infarction (MI)
– 25 patients (17 active, 8 control)
– Sponsored by Cedars-Sinai Medical Center
Lancet, 2012, 21(6): 1121-1135.
Results showed that treatment with CDCs following a heart attack:
• reduced the amount of scar in the heart
• increased the amount of healthy heart muscle
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Scar size and myocardial reserve are
predictors of clinical outcome after heart attack
CDC Therapy with CAP-1001 Reduces
Scar Size & Increased Healthy Heart Muscle
Burns et al, JACC 2002;39:30-6.
Klem et al, JACC 2012;60:408-20.
Wu et al, Heart 2008;94:730-736.
Makkar et al, Lancet 2012;379:895-904.
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CADUCEUS Provides Evidence for Several Groundbreaking Therapeutic Concepts
– Therapeutic regeneration
– Reversibility of “irreversible” injury
– Curative approach vs. stabilization & palliation
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ALLSTAR
CAP-1002 is Next-Generation CDCs
DYNAMIC
HOPE-Duchenne
Population
Allogeneic cells – would provide for “off-the-shelf” product
Heart failure
(post-MI)
Heart failure
(advanced)
DMD-associated
cardiomyopathy
Status
Ph. II – to report Q1 2017
Ph. I – reported
Ph. II – to report Q1 2017
6-month data reported
12-month data pending
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ALLSTAR
Janssen Biotech (J&J)
collaboration
CIRM loan award
Phase II
Phase II enrolling
Data expected Q1 2017
Evaluate safety & POC
in HF post-MI
with ALLO cells
CAP-1002 Clinical Development
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ALLSTAR Phase I results: Showed Improvement in Scar Size
P<0.05*
n=4
14
16
18
20
22
24
26
28
IS (
% L
V)
Infarct Size
Baseline
12 Months
14
16
18
20
22
24
26
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Baseline 12 Months
IS (
% L
V)
Infarct Size
P<0.05#
“Phase II Equivalent” Population = High Dose, w/o DSAs
*by groups t-test # by paired t-test
13
ALLSTAR Phase I results: Showed Improvement in Cardiac Function
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ALLSTAR
Janssen Biotech (J&J)
collaboration
CIRM loan award
Phase II
Phase II enrolling
Data expected Q1 2017
Evaluate safety & POC
in HF post-MI
with ALLO cells
CAP-1002 Clinical Development
Phase I / II
Evaluate safety & POC
in advanced HF
with ALLO cells
6-month data at AHA 2015
12-month data pending
DYNAMIC
NIH grant – $3M
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Overall Cardiac Status Improved in DYNAMIC
AHA, November 2015
6 month data for 2 subjects pending
NYHA Class Physical Activity
I No limitation
II Slight limitation
III Marked limitation
Of the 12 Class III patients who started the trial and were evaluable at
six months for this analysis, 11 (92%) improved by at least one NYHA class.
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Other Clinical Improvements Observed in DYNAMIC
AHA, November 2015
6 Minute Walk Test
& VO2 Max
Quality of Life
6 month data for 2 subjects pending
less is better
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Key Heart Measures Improved in DYNAMIC
Left Ventricular Dynamics & Dimensions
AHA, November 2015
Measurements assessed by echocardiography
6 month data for 2 subjects pending
less is better
DYNAMIC demonstrated an efficacy signal with concordant improvements
in functional status, quality-of-life, and left ventricular function and size.
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ALLSTAR
Janssen Biotech (J&J)
collaboration
CIRM loan award
Phase II
Phase II enrolling
Data expected Q1 2017
Evaluate safety & POC
in HF post-MI
with ALLO cells
CAP-1002 Clinical Development
Phase I / II
Evaluate safety & POC
in advanced HF
with ALLO cells
6-month data at AHA 2015
12-month data pending
DYNAMIC
NIH grant – $3M
Phase I / II
Evaluate safety & POC
in DMD-cardiomyopathy
with ALLO cells
FDA Orphan designation
CIRM grant* – $3.4M
Enrolling
Data expected Q1 2017
HOPE-Duchenne
*pending final approval
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CAP-1002 in Development for Heart Disease
Associated with DMD
– CAP-1002 is orthogonal to dystrophin-correcting therapies
in development, which target skeletal muscle
Expected to be complementary to other DMD therapies
No evidence for other DMD therapies to provide cardiac benefit
FDA Orphan status
Currently being evaluated in a Phase I / II clinical trial
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30
40
50
60
70
80
Baseline Wk3 M2 M3 Wk3 M2 M3
Mdx+CDC
Mdx+Vehicle
ISEV, April 2015
AHA, November 2014
CAP-1002 Improves Cardiac Function and
Exercise Capacity in DMD Model
*** p<0.001 * p<0.05
100160220280340400460520580640700760820
3 4 5 6
CTL
Mdx + CDC
Mdx + vehicle
Week
* *
*** * *
1st injection
EF
(%
)
Repeat Dosing
Me
ters
2nd injection
n=12 Mdx + CDC
n=12 Mdx + vehicle
n=5 CTL (wild-type)
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HOPE-Duchenne Trial Underway
– Phase I / II clinical trial
– Randomized, open label multi-center study (3-4 sites)
12 boys randomized to CAP-1002 infusion
12 boys randomized to ‘usual care’
– Delivered by triple vessel intra-coronary infusion
– Actively enrolling patients
– Preliminary efficacy to be assessed at 6 and 12 months
Halt cardiomyOPathy progrEssion in Duchenne
22
Exosomes:
Next-Generation Regenerative Medicine Platform
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Exosomes are an Emerging Class of Therapeutics
with Broad Potential
– Cell-free technology
– Nanometer-sized vesicles
– Secreted by nearly all cell types
– Rich in RNAs and proteins
– Readily cross cell membranes
– Cell signaling modality
– Capricor has exclusive WW
license to exosomes technology
originating from CDCs from
Cedars-Sinai
Camussi et al, Kidney Int 2010;78:838–848.
24
CDC Exosomes Significantly Improve Cardiac
Structure and Function
0
2
4
6
8
10
12
14
16
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CTRL NHDF-XO MSC-XO CDC-XO
Scar
Mas
s (m
g)
** **
*
Control NHDF-Exosomes
MSC-Exosomes CDC-Exosomes
25
30
35
40
45
50
1 15 30
EF (%
)
Days post MI
Control
CDC-XO
NHDF-XO
MSC-XO
** *
Ibrahim et al, Stem Cell Reports 2014;2:606-619.
Effects not observed with exosomes from other cell types
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Capricor’s CAP-2003 moving into the clinic
– Proof-of-principle has been demonstrated
– CDC exosomes appear to possess regenerative capabilities
– Capricor plans to announce the first indication for its CDC exosome
technology in 1H 2016 (eyes, skin, cancer are in consideration)
– Capricor expects to meet with FDA to discuss clinical development
in 2Q 2016, and to file an IND by YE 2016
26
Cenderitide (CD-NP): A Dual Natriuretic Peptide Receptor Activator
-S-S-
K
L
L
D R I G
S
M
S
G
L G G F
C C
K
G
S
L
G
pGC-B agonist
Anti-fibrotic
Anti-inflammatory
Endothelial regenerating P
S
L
R
D
P
R
P
N
A
P
S
T
S
A
pGC-A agonist
Enhances renal function
Suppresses aldosterone
Promotes cell survival
Resistant to NEP degradation
CNP DNP (C-terminus)
27
Cenderitide is administered via
continuous SC pump
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Cenderitide for Outpatient
and Ambulatory Heart Failure
Target Indication
Prevention of re-hospitalization in patients with a recent acute heart failure admission
– Phase IIa PK/PD Trial
1st arm - 14 patients treated, enrollment complete
Patients with stable chronic heart failure
Trial assessed the safety and tolerability, pharmacokinetics profiles, and pharmacodynamic response to increasing dose levels of Cenderitide
No significant issues with safety or Insulet pump delivery
Early results suggest tolerability and physiologic effect
– Initiated a second study to further assess higher doses
– First portion has completed
– To announce further plans following results
29
Financial Summary
Cash, cash equivalents, and marketable securities
reported at September 30, 2015 $17.2 million
Cash used in operations
in the nine months ended September 30, 2015 $7.2 million
Shares outstanding (November 12, 2015) 16.3 million
30
Senior Management
AJ Bergmann, MBA VP of Finance
Leland Gershell, MD PhD Chief Financial Officer
Deborah Ascheim, MD Chief Medical Officer
Karen Krasney, JD EVP & General Counsel
Rachel Smith, PhD VP of Finance
Houman Hemmati, MD PhD VP of New Therapy Development
Luis Rodriguez-Borlado, PhD VP of Regenerative Therapies
Linda Marbán, PhD Chief Executive Officer
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Board of Directors
Louis Grasmick Founding Investor Linda Marbán, PhD – PRESIDENT
Excigen
George Dunbar, Jr. Aastrom Biosciences
Arboretum Ventures
Earl M. (Duke) Collier, Jr. Genzyme
Joshua Kazam Two River
Kite Pharmaceuticals
Louis Manzo Founding Investor
Gregory Schafer Aduro Pharmaceuticals
Onyx Pharmaceuticals
Frank Litvack, MD – EXECUTIVE CHAIRMAN Conor Medsystems, Savacor
David Musket ProMed Partners
32
Upcoming Milestones
2016 2017
Meet with FDA on exosomes clinical development
Q2
Announce first indication in exosomes program
Complete enrollment in HOPE-Duchenne trial Q3
Report data from Phase I / II HOPE-Duchenne trial
Q1
Report data from Phase II ALLSTAR trial
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Transformative Therapies from Bench to Bedside