Transformative Therapies from Bench to Bedside

(1)

NASDAQ: CAPR

Corporate Presentation

May 2015

Transformative Therapies

from Bench to Bedside

(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 our business are set forth in our 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

our Registration Statement on Form S-1, as filed with the Securities and Exchange Commission on March 6, 2015

and in our Form 10-Q for the quarter ended March 31, 2015, as filed with the Securities and Exchange

Commission on May 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.

(3)

Capricor Therapeutics Overview

Clinical-stage biotechnology company with a diversified

pipeline focusing on cardiovascular diseases including orphan

indications

Peptide

therapy for

heart failure

(Cenderitide)

Cardiac-derived stem

cells (CDCs)

Micro-RNA

Platform

(Exosomes)

3

(4)

Capricor Therapeutics Pipeline

Products

Indication

Preclinical

Phase I/II

Phase II

Phase III

CDCs (CAP-1002)

Cenderitide

CU-NP

Exosomes

Natriuretic Peptides

Micro-RNA Technology

Cell Therapy

Post Myocardial Infarction

Advanced Heart Failure

(Class III and ambulatory Class IV)

Duchenne Muscular Dystrophy

Advanced Heart Failure

(Class III and ambulatory Class IV)

Cardiovascular

(5)

Capricor: Key Metrics

Select Data

(approximate)

As of 3.31.15

Cash

(Includes restricted cash and marketable securities)

$24.5M

Publicly traded: NASDAQ

CAPR

52 week range

$3.05-$10.68

Shares outstanding

16.2M

Fully diluted shares outstanding

23M

Cash through

~Q3 2016

Non-dilutive capital funding to date

$39.5M

Exclusive Licenses

Johns Hopkins University, Cedars-Sinai Medical Center, Mayo

Foundation for Medical Education and Research and The

University of Rome

Headquarters

Los Angeles, CA

Employees

32

(6)

Development of Ischemic Heart Failure

Konstam et al.,

JACC

, 2011

Heart

Failure

(

hours~days

)

Infarct expansion

(weeks~months)

Chronic LV dilation

(days~weeks)

Thinning

(7)

(8)

Lead Product: CDCs (CAP-1002)

Cardiosphere-derived

cells (CDCs)

Cardiospheres

(CSps)

Explant-derived

cells (EDCs)

Explants

Cardiac Tissue

Features

Cardiosphere-Derived Cells (CDCs)

Cell Type

Human cardiac derived stem cell

Characteristics

Panel of cellular markers and secreted factors

Clinical Trials

CADUCEUS

– completed autologous Phase I (n=25), showed regeneration in CDC-treated

post-MI patients

(sponsored by CSMC)

ALLSTAR

– completed Phase I (n=14), now in Phase II with allogeneic CDCs in post-MI patients

DYNAMIC

– ongoing study of allogeneic CDCs in heart failure patients

MOA

Largely paracrine:



Prevent cardiomyocyte apoptosis

(programmed cell death)



Promote cardiomyocyte proliferation and angiogenesis

(cell growth and blood vessel

formation)



Attract endogenous stem cells

(9)

CADUCEUS - Positive First-in-Man Data



Published in Lancet, 2012



Autologous CDCs - 25M cells



Patients with reduced ejection fraction following MI



Sponsored by Cedars-Sinai with Johns Hopkins



Intracoronary delivery



25 patients



17 CDCs



8 Controls

(10)

Makkar et al, Lancet, 2012.

CDC patients had a significant reduction in infarct size.

We hypothesize improvement in clinical outcomes.

CDC Therapy Reduced Scar Size & Increased

Healthy Heart Muscle in the CADUCEUS study

(11)

Effect of Infarct (Scar) Size on Events

Wu, E. et al. Heart 94, 730-736 (2008).

(12)

ALLSTAR Clinical Trial

Collaboration with

Janssen Biotech (J&J),

funded in part by CIRM

Phase II

14 patient trial

Enrolling

Data anticipated:

~Q4 2016-Q1 2017

IND

submitted

Post myocardial

infarction (30 days –

1 year after MI)

NYHA Class III or

ambulatory Class IV heart

failure

Duchenne muscular

dystrophy-related

cardiomyopathy

Orphan designation

granted

Enrollment complete

Data anticipated:

~Q4 2015

Targeting trial initiation:

2H 2015

DYNAMIC Clinical Trial

HOPE Clinical Trial

Funded in part by the NIH

In

d

ica

tio

n

Clin

ical

D

ev

elopm

ent

Sta

tu

s

CDCs: Clinical Development

(13)

ALLSTAR Phase I – 12 month MRI Analysis



ALLSTAR Phase I



Met safety endpoint (1 month)



No control group



Preliminary 12 month MRI analysis on Phase II equivalent

population (defined by tissue type compatibility)



Ejection fraction improved by 5.2%



Relative reduction in scar size of 20.7%



Measurements of viable mass and regional function

also showed quantifiable improvements

(14)

DYNAMIC Clinical Trial

Study Overview



Patient criteria



Ischemic or non-ischemic DCM with LVEF ≤ 35%



NYHA Class III or ambulatory Class IV heart failure



Delivery: Non-occlusive intracoronary infusion in 3 vessels



Trial Design



Feasibility Study - open-label (N=14, single center)



Enrollment complete



Top-line data expected Q4 2015

D

ilated cardiom

Y

opathy i

N

tervention with

A

llogeneic

M

yocard

I

ally-regenerative

C

ells

(15)

(16)

Duchenne Muscular Dystrophy



Prevalence: 1 in 3,500 male births worldwide



~20,000 male children affected in the US (~275,000 worldwide)



DMD is usually fatal; a majority of deaths occur due to

cardiomyopathy



Compelling preclinical data presented at AHA in November 2014



IND submitted 1H 2015



HOPE clinical trial planned for 2H 2015



Intent to complement other dystrophin-correcting therapies for skeletal

muscle



Orphan disease – presents potential billion dollar market opportunity

(17)

Rationale for CDCs Use in DMD



Anti-oxidative



Anti-inflammatory



Anti-apoptotic



Anti-remodeling



Regenerative

CDCs

DMD

pathophysiology



Oxidative/Nitrosative stress



Inflammation



Apoptosis



Remodeling

CDC administration may be beneficial in DMD

cardiomyopathy

Tested in

mdx

mouse model

(18)

mdx

Mouse Model of Duchenne

Muscular Dystrophy



Mimics the target indication, DMD



Aged to the point at which cardiac dysfunction becomes

evident: ≥10 months old

(19)

EF(

%)

***

*

***

p<0.001

*

p<0.05

n=12 Mdx+CDC, Mdx+vehicle

n=5 CTL(WT)

Global Cardiac Function is Improved in

mdx

Mice

50

55

60

65

70

75

Baseline Wk3

M2

M3

Mdx+CDC

Mdx+Vehicle

CTL(WT)

Reference: Cedars-Sinai Heart Institute

Presented at AHA - November 2014, Chicago, IL

*

30

40

50

60

70

80

Baseline Wk3

M2

M3

Wk3

M2

M3

Mdx+CDC

Mdx+Vehicle

***

*

1

st

injection

2

nd

injection

EF(%

)

Presented at ISEV - April 2015, Washington DC

Repeat Dosing

Single Dose

(20)

100

160

220

280

340

400

460

520

580

640

700

760

820

wk3

wk4

wk5

wk6

CTL

Mdx+CDC

Mdx+Vehicle

CDCs Increased Maximal Exercise Capacity

Dista

nc

e(m)

**

n = 6-11

Presented at AHA - November 2014, Chicago, IL

(21)

Duchenne Cardiomyopathy and CDCs



Injection of CDCs into

mdx

hearts



Improves global function



Decreases fibrosis



Improves exercise capacity



Exerts potent anti-oxidant effects



Reverses abnormalities in mitochondrial

abundance, structure and function



Increases cardiomyocyte proliferation and

activation/recruitment of endogenous repair

Presented at AHA - November 2014, Chicago, IL

(22)

Capricor’s CDCs Are Unique

Capricor’s CDCs

are the only

allogeneic,

intracoronary

delivered,

cardiac-derived

stem cells

CDCs

(23)

(24)

Cenderitide: A Unique Protein Drug

-S-S-K

L

D

R I

G

S

M

S

G

L

G

F

C

K

G

S

L

G

NH

2

P

S

L

R

D

P

R

P

N

A

P

S

T

S

CD-NP



Developed by scientists at the Mayo

Clinic and derived from the venom

of the green mamba snake



Cenderitide

:



Cardiac unloading



Renal function preserved



Aldosterone suppressing



Anti-fibrotic, apoptotic, and

hypertrophic



270 patients with acute

decompensated heart failure have

been treated

(25)

Continuous Subcutaneous Infusion Using

the Insulet Omnipod

®

Technology



Current pump delivery systems are robust, simple, and well

tolerated



In use by more than 300,000 patients worldwide



Pump use is simple for all types of patients, not just diabetics



Continuous delivery is ideal for worry-free dosing throughout the

day and night

Sample shown: Omnipod®

Press Start

Apply the Pod

Fill the Pod

(26)

Cenderitide’s Development

The Opportunity

+

1

st

Phase II clinical

trial complete

K

L

D

R I G S

M

S

G

L

G

F

C

K

G

S

L

G

P

S

L

R

D

P

R

P

N

A

P

S

T

S

A

(27)

Cenderitide

for Outpatient

and Ambulatory Heart Failure

Target

Indication

Prevention of re-hospitalization in patients with a

recent acute heart failure admission as well as

other potential indications

Phase II Trial enrollment complete



14 patients treated



Patients with stable chronic heart failure



Trial assessing the safety and tolerability, pharmacokinetics

profiles, and pharmacodynamic response to increasing dose

levels of Cenderitide



Early results suggest tolerability and physiologic effect



Will announce further plans in late 2015, early 2016

(28)

Exosomes: Micro-RNA Platform

Technology

(29)

Exosomes: Micro-RNA Platform Technology



Nanometer-sized lipid-bilayer

vesicles



Rich in miRNAs



Present in virtually all body

fluids



Released by nearly all cell

types



Potential for broad therapeutic

applicability

(30)

CDCs Release Bioactive Exosomes that Recapitulate

their Therapeutic Effects in Cardiac Injury

CTRL

Skin-Exosomes

CDC-Exosomes

Ibrahim et al.,

Stem Cell Reports

, 2014

25

30

35

40

45

50

1

15

30

EF

(%)

Days post MI

Control

CDC-XO

Skin-XO

**

*

(31)

CDC Exosomes: Isolation Methods

and Phenotype

BATCH ANALYSIS REPORT

Nanoparticle Tracking Analysis (NTA) Version 2.3 Build 0034

0 100 200 300 400 500 600 700 800 900 1000 Size (nm) C o n c e n tr a ti o n ( E 6 p a rt ic le s /m l) ____ 155_10x Media_07231401 ____ 155_10x Media_07231402 ____ 155_10x Media_07231403 ____ 155_10x Media_07231404 ____ 155_10x Media_07231405 3.77 Size / Concentration 0 100 200 300 400 500 600 700 800 900 1000 Size (nm) C o n c e n tr a ti o n ( E 6 p a rt ic le s /m l) 3.56

Averaged Size / Concentration

Red error bars indicate +/- 1 standard error of the mean

Operator: GEA

Sample: CDCs CD63 20ul

Included files: 155_10x Media_07231401

155_10x Media_07231402 155_10x Media_07231403 155_10x Media_07231404 155_10x Media_07231405 Date/Time of Report 23/07/2014 12:07:08 Dispersant/Diluent: PBS Concentration: 1:100 PBS

BATCH AVERAGE RESULTS:

Size Distribution: Mean: 165 +/- 9.7 nm Mode: 121 +/- 3.4 nm SD: 75 +/- 15.8 nm D10: 90 +/- 2.9 nm D50: 146 +/- 2.2 nm D90: 265 +/- 31.9 nm Total Concentration: 19.27 +/- 0.41 particles/frame

4.07 +/- 0.08 E8 particles/ml Total Completed Tracks: 3851

Average Drift Velocity: 1557 nm/s

CAPTURE SETTINGS

Camera Type: sCMOS

Shutter length: 37.3899 ms

Shutter setting: 1495

Camera gain: Varied

Frame rate: Varied

ANALYSIS SETTINGS

Background Extract: On

Detection Threshold: 10 - Multi

Blur: AUTO

Min track length: AUTO

Min expected size: AUTO

Temperature: 24.6, 24.7, 24.8, 24.8, 24.8 oC Viscosity: 0.90, 0.89, 0.89, 0.89, 0.89 cP

WARNINGS

Vibration detected during analysis

3.06

Par

tic

le

#

(1

0

8

)/mL

155

BATCH ANALYSIS REPORT

0 100 200 300 400 500 600 700 800 900 1000 Size (nm) C o n c e n tr a ti o n ( E 6 p a rt ic le s /m l) ____ 220_10x Media_07231401 ____ 220_10x Media_07231402 ____ 220_10x Media_07231403 ____ 220_10x Media_07231404 ____ 220_10x Media_07231405 5.84 Size / Concentration 0 100 200 300 400 500 600 700 800 900 1000 Size (nm) C o n c e n tr a ti o n ( E 6 p a rt ic le s /m l) 4.99

Operator: GEA

Included files: 220_10x Media_07231401

220_10x Media_07231402 220_10x Media_07231403 220_10x Media_07231404 220_10x Media_07231405 Date/Time of Report 23/07/2014 12:23:39 Dispersant/Diluent: PBS Concentration: 1:100 PBS

BATCH AVERAGE RESULTS:

CAPTURE SETTINGS

Camera Type: sCMOS

Shutter length: Varied

Camera gain: 253

Frame rate: Varied

Blur: AUTO

WARNINGS

4.99

220

BATCH ANALYSIS REPORT

0 100 200 300 400 500 600 700 800 900 1000 Size (nm) C o n c e n tr a ti o n ( E 6 p a rt ic le s /m l) ____ HT_10x d15 Med_07241401 ____ HT_10x d15 Med_07241402 ____ HT_10x d15 Med_07241403 ____ HT_10x d15 Med_07241404 ____ HT_10x d15 Med_07241405 3.80 Size / Concentration 0 100 200 300 400 500 600 700 800 900 1000 Size (nm) C o n c e n tr a ti o n ( E 6 p a rt ic le s /m l) 3.48

Operator: GEA

Included files: HT_10x d15 Med_07241401

HT_10x d15 Med_07241402 HT_10x d15 Med_07241403 HT_10x d15 Med_07241404 HT_10x d15 Med_07241405 Date/Time of Report 24/07/2014 09:45:49 Dispersant/Diluent: PBS Concentration: 1:100 PBS

BATCH AVERAGE RESULTS:

CAPTURE SETTINGS

Camera Type: sCMOS

Shutter length: Varied

Camera gain: 169

Frame rate: Varied

Blur: AUTO

WARNINGS

Vibration detected during analysis

3.48

iner

t

100

200

300

400

500

Particle Size (nm)

Nanosight

100

200

300

400

500

100

200

300

400

500

CDCs (lines 155 or 220) or inert

NHDFs (dermal fibroblasts)

Culture in SF Media

(15 days)

Collect Conditioned

Media



Precipitate by ExoQuick (

in

vivo

studies)



Isolate by ultracentrifugation

(

in vitro

studies in iPS cells)

Exosome Isolation

CD63

(~53kDa)

CD9

(~28kDa)

HSP70

(~70kDa)

CD81

(~26kDa)

Ex

os

omal

Ma

rke

rs

155 220

CD105

(~80kDa)

C

D

C

Ma

rke

r

Reference: Cedars-Sinai Heart Institute

Presented at ISEV - April 2015, Washington DC

3.48

(32)

EL Andaloussi et. Al. Nat Rev Drug Discov. 2013 May;12(5):347–57.

Advantages for Exosomes for

Tissue Repair



Novel delivery vehicle reproducing the beneficial

effects of living cells



Natural capacity to protect their bioactive cargo



Potential for simple manufacturing protocols



Reduced immunogenicity

(33)

Exosomes

as a Potential New Therapeutic

Product

Description

Product

Function

Product

Development

Clinical

Status

Ongoing pre-clinical work, developing

manufacturing and pre-commercial scale up

Promotes similar paracrine effects of CDCs;

prevent apoptosis, proliferation, angiogenesis,

anti-fibrotic

Released by nearly all cell types and body fluids,

these are nanometer sized lipid-bilayer vesicles

rich in miRNAs

Targeting IND in 2016

(34)

2015 Targeted Milestones



1H 2015



Complete DYNAMIC trial enrollment –

completed



Complete Cenderitide Phase II enrollment –

completed



Receive Orphan Designation for DMD –

completed



Submit IND for DMD-associated cardiomyopathy –

completed



2H 2015



Initiate HOPE-DUCHENNE trial



Report initial DYNAMIC results



Report initial Cenderitide results



Announce development program for natriuretic peptides



Announce 1

st

indication for exosomes

(35)

Senior Management & Board of Directors

Senior Management



Chief Executive Officer

Linda Marbán, Ph.D. (Founder)



Scientific Advisory Board Chairman

Dr. Eduardo Marbán (Founder, JHU,

Cedars-Sinai)



VP of Research and Development

Rachel Smith, Ph.D. (Johns Hopkins)



EVP & General Counsel

Karen Krasney, J.D. (Biosensors)



VP of Medical Affairs

Andrew Hamer, M.D. (Chairman –

New Zealand Cardiac Network)



VP of Clinical Operations

Shane Smith (Nektar, Genentech)

Board of Directors



Executive Chairman

Frank Litvack, M.D. (ConorMed)



Linda Marbán, Ph.D.



Dave Musket (ProMed Partners)



Earl M. (Duke) Collier, Jr.

(Genzyme)



George W. Dunbar, Jr.

(Aastrom)



Joshua Kazam (Kite, Two-River)



Gregory Schafer (Aduro,

Onyx)



Louis Manzo (Investor)



Louis J. Grasmick (Investor)