Download - Bioheart (OTC: BHRT; Twitter: $BHRT)

1

BIOHEART INC.April 2011

OTC: BHRT.OB

2

Forward-Looking Statement

Except for historical matters contained herein, statements made in this presentation are forward-looking and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Without limiting the generality of the foregoing, words such as “may”, “will”, “to”, “plan”, “expect”, “believe”, “anticipate”, “intend”, “could”, “would”, “estimate”, or “continue” or the negative other variations thereof or comparable terminology are intended to identify forward-looking statements.

Investors and others are cautioned that a variety of factors, including certain risks, may affect our business and cause actual results to differ materially from those set forth in the forward-looking statements. These risk factors include, without limitation, (i) our ability to obtain additional financing; (ii) our ability to control and reduce our expenses; (iii) our ability to establish a distribution network for and commence distribution of certain products for which we have acquired distribution rights; (iv) our ability to timely and successfully complete our clinical trials; (v) the occurrence of any unacceptable side effects during or after preclinical and clinical testing of our product candidates; (vi) the timing of and our ability to obtain and maintain regulatory approvals for our product candidates; (vii) our dependence on the success of our lead product candidate; (viii) our inability to predict the extent of our future losses or if or when we will become profitable; (ix) our ability to protect our intellectual property rights; and (x) intense competition. The Company is also subject to the risks and uncertainties described in its filings with the Securities and Exchange Commission, including the section entitled "Risk Factors" in its Annual Report on Form 10-K for the year ended December 31, 2010.

3

Company Thesis

Bioheart is dedicated to the discovery and development of myoblast and stem cell therapies for heart damage:MyoCell ®

An autologous cell therapy comprised of muscle derived stem cells for congestive heart failure.

MyoCell ® SDF-1

An autologous cell and gene therapy comprised of muscle derived stem cells transduced to express the protein stromal derived factor – 1 for congestive heart failure.

4

Heart Disease is the Leading Cause of Death Worldwide According to the American Heart Association,

approximately 5.7 million Americans suffer from congestive heart failure (CHF).

The cost of hospitalization and treatment for heart failure is twice that of all forms of cancer combined.

Treatment with drugs and devices is available but not all patients return to a normal lifestyle.

Myoblasts represent the most advanced cell therapy that can effectively be targeted to this patient population.

5

MyoCell® Cell Therapy Overview Muscle stem cell-based therapy designed to

treat heart damage by growing new muscle in damaged heart tissue.

Uses myoblasts (muscle stem cells)

• Patient-derived; reduces risk of tissue rejection

• Committed to forming muscle, will not differentiate into other cell types or over-proliferate

• Tolerates low-oxygen conditions present in scar tissue

Large potential savings in healthcare costs

6

Myoblast Engraftment Post-Transplantation

Contractile muscle tissue growing in the scarred portion of the heart following treatment with myoblast injections.

Human Heart, Proof of Concept

* Hagege et al., Viability and Differentiation of Autologous Skeletal Myoblast Grafts in Ischemic Cardiomyopathy, Lancet, Vol. 361, 2003: 491-492

7

MyoCell: Heart Failure Treatment Process

Scar tissue following heart

attack

Injection of skeletal myoblasts into scar

tissue using deflecting-tip

catheter

Cell manufacturing following thigh muscle biopsy

1

3

2

8

Trial# of

PatientsStatus Primary Endpoints

EU Phase I/II 5 Phase I15 Phase I/II

CompletedQ2 2003

• Serious adverse events• Global ventricular function

MYOHEART(US, Phase I)

20

CompletedFinal Patient

TreatedQ4 2006

• Serious adverse events

SEISMIC(EU, Phase II-a with Control)

40(14 control)

CompletedFinal Patient

TreatedQ3 2007

• Serious adverse events• LVEF

MARVEL Trial(N. Am./EU: Phase II/III, Double-blind, Placebo-controlled)

150 anticipated

(50 controls)

Stage 1 Results AnnouncedFirst Patient Enrolled and

TreatedQ4 2007

• Serious adverse events• 6-minute walk test• Quality of life score

Bioheart Has Addressed CHF with Myocell

Including third-party studies, myoblasts have been evaluated in at least 11 clinical trials involving more than 345 enrollees and

more than 255 treated patients

9

36%

41%

45%

30

32

34

36

38

40

42

44

Baseline 3 month 6 month

Journal of the American College of Cardiology, Vol. 42, No. 12, 2003, Serruys, Smits et al. Study sponsored by Bioheart, Inc.

LVEF Measured via LAO LV Angio. 3 month, p=0.009; 6 month, p=0.23. N = 5.

Percutaneous Intramyocardial Transplantation of Autologous Myoblasts: Bioheart First-In-Man Experience

LVEF

(%)

10

Percutaneous Intramyocardial Transplantation of Autologous Myoblasts – BIOHEART Phase I/II Trial

Results for these trials were not statistically significant due, in part, to the limited number of patients treated.

I31%

II52%

III8%

IV9%

Baseline 6 Months 12 Months

I0%

II31%

III54%

IV15%

I38%

II62%

III0%

IV0%

NYHA Class Improvement

N = 13 N = 13 N = 13

LVEF: Mean Baseline = 34.4% + 7.4 Mean 12-Month Follow-up = 36.6% + 9.6

11

Measurements via PV Loop, n=5.

Absolute Improvement (%)

25

30

35

40

45

p = .09

Baseline 6 - Month

LVEF CO LVESV

Absolute Improvement (mL)

100

120

140

160

180

200

p = .04

Baseline 6 - Month

33

41190

150

Absolute Improvement (L/min.)

4

4.5

5

5.5

6

p = .05

Baseline 6 - Month

4.6

5.6

Percutaneous Intramyocardial Transplantation of Autologous Myoblasts – BIOHEART Phase I/II Trial

12

Bioheart Percutaneously Delivered Myoblasts Clinical Trial Data Summary

EU FIM, Phase I/II Adjudicated Data (n = 5+15)

Safety• 2 patient deaths (10%)

Efficacy

• 4/5 of patients improved one heart failure class

• 1/3 of patients improved two heart failure classes

• 1/3 of patients experience ~ 35% relative improvement in LVEF

• 15.3% improvement in Wall

Motion Score Index via stress echo

• 13% reduction of LVED volume

• 7 arrhythmic events reported• 5 possibly related to cell therapy (25%)• All occurred during first 3 mos. post implant• Anti-arrhythmic medication not prophylactically prescribed

• PVCs peaked at 3-weeks but were reduced from 1.89% at baseline to 0.04% at 12 mo. follow-up

Bioheart Phase I/II Trial (005/006).

13

47 Patients Randomized:

ICD Patients: 31 MyoCell®, 16 Standard Medical Therapy

Treatment Arm (MyoCell ® 150-800 x 10

6)

26 ICD Patients

Control Arm(Standard Medical Therapy)

14 ICD Patients

Baseline Evaluation

Screening: 62 ICD Patients

15 Screen Fails

5 Withdrawals* 2 Withdrawals**

* All 5 treated patients withdrew due to changes in German biopsy regulations.** Both control patients withdrew after knowledge of randomization allocation.

Bioheart Percutaneously Delivered Myoblasts EU Phase II Trial (SEISMIC)

14

SEISMIC NYHA heart failure class

Improvement

Myoblast therapy

Control therapy

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

N=26 N=23 N=22 N=20

N=14 N=9 N=12 N=13

BL 1 mo 3 mo 6 mo

BL 1 mo 3 mo 6 mo

15

SEISMIC

+60.3 m + 54.1

-0.2 m ± 177.1

Treatment

N=26 N=21 N=19

ControlControl

N=14 N=12 N=13

448 m 441 m

406 m 466 m

6-Minute Walk Test Improvement

Difference BetweenBaseline and 6 Months

16

SEISMIC Response to Treatment NYHA HF / 6MWT / MLFQ / LVEF

17

MYOHEART US Phase I Study Flow

Clinical Sites: Columbia Presbyterian, Cleveland Clinic, Mayo Clinic,

Minneapolis Heart, St. Joseph’s / ACRI

Core Lab: Gentiae Clinical Research

2 injections(.25 cc)



First Cohort (n=5)25 x 106 cells

30-Day Safety Evaluation

Second Cohort (n=5)75 x 106 cells


Third Cohort (n=5)225 x 106 cells


Fourth Cohort (n=5)675 x 106 cells


18

MYOHEART 6MWT

Average 6 Minute Walk Test – All CohortsAverage 6 Minute Walk Test – All Cohorts

350

400

450

500Baseline 3-Month 6-Month 12-Month

6MW

T

(me

ters

)

N=20

422

474471

N=18 N=15

0

25

50

75

100 Change BL:3-MonthChange BL:6-MonthChange BL:12-Month

4736

N=15

6MW

T

(me

ters

)

N=18

All PatientsAll Patients Paired AnalysisPaired Analysis

p = .0074p = .0074 p = .2126p = .2126

474

N=17

42

p = .1367p = .1367

N=17

19

MYOHEART MLHFQ

Average Minnesota Living with Heart Failure ScoreAverage Minnesota Living with Heart Failure ScoreAll CohortsAll Cohorts

20

40

60

80Baseline 3-Month 6-Month 12-Month

ML

HF

S

co

re

N=20

51

34 33

N=19 N=18

-25

-20

-15

-10

-5

0

5

10Change BL:3-MonthChange BL:6-MonthChange BL:12-Month

-14-16

N=19N=18

All PatientsAll Patients Paired AnalysisPaired Analysis

p = .0016p = .0016 p = .0004p = .0004

ML

HF

S

co

re

30

N=18N=18

-18

p = .0006p = .0006

20

Bioheart MARVEL Program

Unique Features and Goals

21

MARVEL Program Study Objectives / End Points

Overall objective• Assess the safety and efficacy of MyoCell® in

CHF patients post myocardial infarction(s) using the MyoStar® and NOGA XP®

Primary safety end point• Incidence of SAEs at 3 and 6 months post

implantation.

Co-Primary efficacy end point• Changes in 6-minute walk distance or quality

of life.

Secondary efficacy end points• Changes in LVEF, LV volume, wall motion

indices, BNP, NYHA class, and frequency and nature of re-hospitalizations.

22

p=0.50

MARVEL-1: Mean Change in 6-Minute Walk Distance (meters)

n=6 n=7 n=6

23

MARVEL-1 Arrhythmia Analysis: Myocell® Patients

Myocell® Txt

14 Patients

No Amiodarone Txtn= 7

4 Patients4 Episodes VT

Amiodarone Started at Implant or

Stoppedn=3

Amiodarone Started at Bx

n=4



0 Episodes VT1 Patient

1 Episode VT

Amiodarone started

Amiodarone continued

24

Competitive Advantage1. Time to market

Bioheart’s technology is authorized for Phase II/III US trials

2. Bioheart has Intellectual Property and technological exclusivity that protects freedom of operation Extensive Patent portfolio and 10+ years of

development of proprietary methods3. Bioheart’s product focuses on a unique

mechanism of action Myoblasts have been shown to be the only

effective cell-based therapy to grow new muscle for treatment of CHF

25

Competition – Congestive Heart Failure

Company Cell Type Development Phase Delivery Method Bioheart, Inc. Myoblasts Phase II/III – initiated;

150 patients Intramyocardial delivery

Advanced Cell Technology

Myoblasts Phase II - trial auth by FDA; 120 patients

Intramyocardial delivery

Aastrom Biosciences Bone Marrow- derived Cells

Phase II – enrollment complete; 40 patients


Angioblast/Mesoblast Systems

Allogeneic Mesenchymal Precursor Cells

Phase II - not recruiting; 60 patients


Cardio3 BioSciences Bone Marrow-derived Mesenchymal Cardiopoietic Cells

Phase II – enrollment complete; 45 patients


Miltenyi Biotec CD133+ Marrow Cells

Phase II – recruiting; 142 patients

Surgical delivery during CABG

Theravitae Angiogenic Cell Precursors

Phase I – recruiting Surgical delivery during CABG

Aldagen ALDH Bright Marrow-derived Cells

Phase I – Complete; 20 patients


Geron Embryonic Stem Cells

Preclinical N/A

26

Myoblast – Cell culture Process Development

2002 Q1 2002 Q2 2002 Q3 2002 Q4 2003 Q1 2003 Q2 2003 Q3 2003 Q4 2006 Q12004 Q1 2004 Q2 2004 Q3 2004 Q4 2005 Q1 2005 Q42005 Q32005 Q2Developed scaled up procedure in Roller Bottles

Developed specialized proprietary media

Established scaled up procedures using cell factories - reduced labor time, less manipulations

Developed Transport media to preserve biopsy and cells shipped to patient

Semi-closed system with luer locks

Developed specialized enzymes

Growth Factor improvement

Full serum screen - Establish best lot for optimal growth of cells

Improved QC release testing for Myoblast Identity

Developed closed system with sterile welding

Optimized mincing technique - reduced fibroblast contamination

Optimized seeding density

Optimized confluence harvest times

Developed improved proprietary media - Reduced cell culture failure due to donor variability

Reduced cell culture time and increased cell yield and quality

Optimized growth factors in media

Developed quantitative release tests for identity and potency of myoblasts

Reduced animal derived raw materials used in process

Validated specialized shipping containers for maintaining product temperature

Manufacturing process is protected, scalable and reliable

27

Myoblasts vs. Bone Marrow Stem Cells for Cardiac

• Characteristic of the bone marrow cells (mainly MSCs):– cells in contact with bone tend towards differentiating

into bone…when cells transplanted into chronic myocardial infarct, tend towards differentiating into fibrosis.

– “it is hard to believe that bone marrow cells could recolonize the chronically infarcted myocardium with new cardiac muscle fibers.”

Combined Transplantation of Skeletal Myoblasts and Mesenchymal Cells (Cocultivation) in Ventricular Dysfunction After Myocardial Infarction. Souza et al., Arg Bras Cardiol. 2004 Oct; 83(4):294-9; 288-93.

•“The transplantation of skeletal myoblasts has proved to be effective in the infarcted myocardium, because those cells can differentiate into viable muscle amidst myocardial fibrosis.”

28

Bone Marrow Mesenchymal Stem Cell Study

• “The labeled MSC population trapped within the implantation site surrounded by fibrous tissue appeared poorly differentiated, with high nucleus/cytoplasm ratio.”

• “Within the scar, they (MSC’s) appeared unorganized and had fibroblast-like morphology.”

• “cells appeared to have differentiated into fibroblasts, cardiomyocytes, endothelial cells and even adipocytes.”

– Ray Chiu, M.D., Ph.D.

29

Bone Marrow Stem Cells Do Not Convert to Muscle

•"Our studies show that only the satellite cells, located near muscle fibers, can give rise to new muscle cells. Contrary to previous studies, precursor cells from bone marrow or other blood-forming tissues did not change their destiny to become muscle cells." •“The results show that adult stem cells that are committed to the blood lineage do not normally differentiate into muscle cells.” •“The only cells that had full potential to generate muscle cells were derived from muscle, not from transplanted bone-marrow or blood-forming stem cells.”Amy J. Wagers, Ph.D., Investigator in the Developmental and Stem Cell Biology Research Section at Joslin Diabetes Center and Assistant Professor of Pathology at Harvard Medical School. November 11, 2004.

30

Bioheart: The FDA Approved REGEN Trial

Next Generation: MyoCell® SDF-1

Increased muscle formation Increased blood vessel supply

Endogenous circulating stem cells attracted to injury by chemokine

proteins

Damaged area secretes chemokine

proteins

Adult stem

cells

SDF-1 Cells

Four years of sponsored animal studies have demonstrated that 2nd generation MyoCell ® SDF-1 provides significantly higher levels of improvement than the first

generation MyoCell ® composition.

31

REGEN Trial – MyoCell SDF-1 Preclinical testing in animals has been both safe

and efficacious with double the improvement over MyoCell

FDA clearance received for a 15 patient, 3 center Phase I study– Dose Escalation – 3 cohorts: 200 million, 400 million and

800 million cells

First ever approval for a combination gene and cell therapy for the treatment of cardiovascular disease.

32

Manufacturing MyoCell

Currently at Bioheart’s Headquarters in Florida Current facility sufficient for next two years and able to

be expanded Capacity

• One Shift: 15 patients/month• Two Shifts: 25 patients/month• Three Shifts: 30-60 patients/month

Ability to add capacity in Florida if expanded with additional suites

Other Locations to be Ramped Up as OUS business grows Korea The Netherlands

37

BIOHEART INC.April 2011

OTC: BHRT.OB