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Bioheart (OTC: BHRT; Twitter: $BHRT) seeks to be the "go to technology partner for heart failure specialists and their patients".
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BIOHEART INC.April 2011
OTC: BHRT.OB
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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.
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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.
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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.
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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
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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
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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
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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
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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
(%)
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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
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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
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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).
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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)
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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
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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
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SEISMIC Response to Treatment NYHA HF / 6MWT / MLFQ / LVEF
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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)
6 injections(.25 cc)
18 injections(.25 cc)
First Cohort (n=5)25 x 106 cells
30-Day Safety Evaluation
Second Cohort (n=5)75 x 106 cells
30-Day Safety Evaluation
Third Cohort (n=5)225 x 106 cells
30-Day Safety Evaluation
Fourth Cohort (n=5)675 x 106 cells
27 injections(.50 cc)
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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
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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
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N=18N=18
-18
p = .0006p = .0006
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Bioheart MARVEL Program
Unique Features and Goals
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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.
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p=0.50
MARVEL-1: Mean Change in 6-Minute Walk Distance (meters)
n=6 n=7 n=6
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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
2 Patients2 Episodes VT
0 Patients0 Episodes VT
0 Episodes VT1 Patient
1 Episode VT
Amiodarone started
Amiodarone continued
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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
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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
Intramyocardial delivery
Angioblast/Mesoblast Systems
Allogeneic Mesenchymal Precursor Cells
Phase II - not recruiting; 60 patients
Intramyocardial delivery
Cardio3 BioSciences Bone Marrow-derived Mesenchymal Cardiopoietic Cells
Phase II – enrollment complete; 45 patients
Intramyocardial delivery
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
Intramyocardial delivery
Geron Embryonic Stem Cells
Preclinical N/A
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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
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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.”
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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.
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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.
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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.
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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.
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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
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BIOHEART INC.April 2011
OTC: BHRT.OB