from Bench to Bedside · Capricor: Key Metrics Select Data (approximate) As of 3.31.15 Cash...

NASDAQ: CAPR

Corporate Presentation

June 2015

Transformative Therapies

from Bench to Bedside

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.

2

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

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

4

CELL THERAPY TECHNOLOGY

Lead Product: CDCs (CAP-1002)

Cardiosphere-derived

cells (CDCs)

Cardiospheres

(CSps)

Explant-derived

cells (EDCs)ExplantsCardiac 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

Anti-fibrotic (anti-scarring)

6

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

7

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

8

Advantages of Allogeneic CDCs

Donors pre-screened by organ procurement organizations

Single donor permits manufacturing of many doses

Freezing permits off-the shelf product availability

COGS reduced by 10X compared to autologous cells

Patient Dose of CAP-1002

9

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

Indic

ation

Clinic

al

Develo

pm

ent

Sta

tus

CDCs: Clinical Development

10

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

11

Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy

Prevalence: 1 in 3,500 male births worldwide

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

DMD is 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

Reference: McNeil et. al, Muscle & Nerve, 2010

13

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 14

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

Reference: Cedars-Sinai Heart Institute

15

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)


Presented at AHA - November 2014, Chicago, IL

* *

30

40

50

60

70

80

Baseline Wk3 M2 M3 Wk3 M2 M3

Mdx+CDC

Mdx+Vehicle

*** * *

1st injection 2nd injection

EF(%

)

Presented at ISEV - April 2015, Washington DC

Repeat DosingSingle Dose

16

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

Dis

tance

(m)

** ** ** **

n = 6-11



17

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



18

Natriuretic Peptide Technology

Cenderitide: A Unique Protein Drug

-S-S-

K

L

L

DR I G

S

M

S

G

LGGF

C C

K

G

S

L

G

NH2

P

S

L

R

D

P

R

P

N

A

P

S

T

S

A

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 treated20

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 StartApply the Pod Fill the Pod

21

Cenderitide’s Development

The Opportunity

+1st Phase II clinical

trial complete

K

L

L

DR I G

S

M

S

G

LGGF

C C

K

G

S

L

G

P

S

L

R

D

P

R

P

N

A

P

S

T

S

A

22

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

23

Exosomes: Micro-RNA Platform

Technology

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

25

CDCs Release Bioactive Exosomes that Recapitulate

their Therapeutic Effects in Cardiac Injury

CTRLSkin-ExosomesCDC-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

***

26

CDC Exosomes: Isolation Methods

and Phenotype

BATCH ANALYSIS REPORTNanoparticle Tracking Analysis (NTA) Version 2.3 Build 0034

0 100 200 300 400 500 600 700 800 900 1000

Size (nm)

Co

nce

ntr

atio

n (

E6

part

icle

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)

Co

nce

ntr

atio

n (

E6

part

icle

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

3.06Pa

rtic

le #

(1

08)/

mL

155


0 100 200 300 400 500 600 700 800 900 1000

Size (nm)

Co

nce

ntr

atio

n (

E6

part

icle

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


0 100 200 300 400 500 600 700 800 900 1000

Size (nm)

Co

nce

ntr

atio

n (

E6

part

icle

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






Mode: 134 +/- 4.4 nm

SD: 69 +/- 3.7 nm

D10: 96 +/- 2.2 nm

D50: 153 +/- 4.0 nm

D90: 255 +/- 9.8 nm





CAPTURE SETTINGS

Camera Type: sCMOS

Shutter length: Varied


Camera gain: 253

Frame rate: Varied

ANALYSIS SETTINGS



Blur: AUTO



Temperature: 25.0, 25.0, 25.1, 25.1, 25.1 oC

Viscosity: 0.89, 0.89, 0.89, 0.89, 0.89 cP

WARNINGS

4.99

220


0 100 200 300 400 500 600 700 800 900 1000

Size (nm)

Co

nce

ntr

atio

n (

E6

part

icle

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


0 100 200 300 400 500 600 700 800 900 1000

Size (nm)

Co

nce

ntr

atio

n (

E6

part

icle

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






Mode: 125 +/- 6.6 nm

SD: 59 +/- 2.0 nm

D10: 94 +/- 1.0 nm

D50: 142 +/- 2.2 nm

D90: 243 +/- 4.1 nm





CAPTURE SETTINGS

Camera Type: sCMOS

Shutter length: Varied


Camera gain: 169

Frame rate: Varied

ANALYSIS SETTINGS



Blur: AUTO



Temperature: 23.1, 23.2, 23.3, 23.4, 23.4 oC

Viscosity: 0.93, 0.93, 0.92, 0.92, 0.92 cP

WARNINGS

Vibration detected during analysis

3.48

inert

10

0

20

03

00

40

0

50

0

Particle Size (nm)

Nanosight

10

0

20

03

00

40

0

50

0

10

0

20

03

00

40

0

50

0

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)

Exoso

som

al

Mark

ers

155 220

CD105 (~80kDa)CD

C

Mark

er


Presented at ISEV - April 2015, Washington DC

3.48

27

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

28

Capricor Investment Opportunity

Ongoing Phase II clinical trials with 2 product candidates

IND for Duchenne Muscular Dystrophy Indication under review

New cell free regenerative medicine platform

technology

Operational leverage - $39.5M of non-dilutive capital since

inception

License Option and Development Collaboration with

Johnson and Johnson

Deep scientific and clinical expertise in target markets

~16-18 months cash on hand29

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 1st indication for exosomes 30

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)

31

Date post:	24-Jul-2020
Category:	Documents
Upload:	others
View:	3 times
Download:	0 times

from Bench to Bedside · Capricor: Key Metrics Select Data (approximate) As of 3.31.15 Cash...

Documents