1. Final Results of a Phase II-a, Randomized, Open-Label Trial to Evaluate Intramyocardial Autologous Skeletal Myoblast Transplantation in Congestive Heart Failure Patients: The SEISMIC Trial Patrick W. Serruys, MD PhD Eric J Duckers, MD PhD on behalf of the BIOHEART European SEISMIC study investigators American College of Cardiology Late-Breaking Clinical Trials April 1, 2008, 11:15 – 11:25 am

2. Patrick W. Serruys, MD PhD Declares no conflicts of interest relating to this presentation

3. – Phase II-a, open-label, 2:1 randomized, controlled, multi-center study – P.I.: Patrick W. Serruys – Sponsor: Bioheart, Inc. Sunrise, Florida, USA – Blinded analysis by core facilities – Health Decisions – Data Management / Statistics, CRO – Synarc – Echo, MUGA Core-Lab – Spacelabs – Holter Core-Lab – Pivotal – Haematology / Viral Core-Lab Percutaneous Intramyocardial Transplantation of Autologous Myoblasts: BIOHEART SEISMIC* Trial * Safety and Effects of Implanted (Autologous) Skeletal Myoblasts (MyoCell ® ) using an Injection Catheter = SEISMIC Trial

4. Overall Objective: To assess the safety and efficacy of MYOCELL ® therapy on myocardial function in CHF patients post MI(s). Primary Safety Endpoint –Defined Serious Adverse Events (SAEs) at 3 & 6 mos Bioheart EU Phase II-a Trial – SEISMIC Secondary Safety Endpoints –Holter monitoring, 12-lead ECG data, frequency of ventricular arrhythmias –Safety of the use of the MyoCath ® injection catheter by Adverse Event (AE) assessment –Number and mean length of stay for hospitalizations Relation between an adverse event and the test article was determined by the Investigator on the basis of his or her clinical judgment fatal or life-threatening events prolonged or required hospitalization sustained arrhythmia for > 30 seconds documented worsening of congestive heart failure resulting in permanent impairment or surgical intervention to preclude permanent impairment of a body function –Medical and scientific judgment by the DSMB committee was exercised when classifying events as serious

5. SEISMIC Significant Adverse Events Study protocol defines SAEs as any adverse events meeting one or more of the following: Fatal Life-threatening Requiring in-patient hospitalization not specifically required by the protocol or is elective Resulting in permanent impairment or surgical intervention to preclude permanent impairment of a body function Additionally, medical events that may not result in death, be life-threatening, or require hospitalization may be considered SAEs when they jeopardize the patient. Medical and scientific judgment by the DSMB committee is exercised when classifying events as serious Relation between an adverse event and the test article will be determined by the Investigator on the basis of his or her clinical judgment

6. Overall Objective: To assess the safety and efficacy of MYOCELL ® therapy on myocardial function in CHF patients post MI(s). Primary Efficacy Endpoint: –Change in LVEF at 3 & 6 mos. by MUGA compared with baseline Secondary Efficacy Endpoints: –QOL assessment, 6-min. walk, NYHA class –Hospitalization, readmissions or the need for medical treatment outside of hospitalizations –Global and regional contractility by contrast aided- Dobutamine Stress Echo and Tissue Doppler Imaging Bioheart EU Phase II-a Trial – SEISMIC

7. 47 Patients Randomized: ICD Patients: 31MyoCell ®, 16Standard Medical Therapy Treatment Arm (MyoCell ® 150-800 x 10 6 ) 26 ICD Patients Control Arm (Standard Medical Therapy) 14ICD 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.

8. 1.Pr. Patrick Serruys, Rotterdam, the Netherlands (PI) 2.Dr. Jozef Bartunek, Aalst, Belgium 3.Pr. Victor Legrand, Liege, Belgium 4.Dr. Walter Van Mieghem, Genk, Belgium 5.Pr. Christoph Nienaber, Rostock, Germany 6.Pr. Joachim Schofer, Hamburg, Germany 7.Pr. Christoph Hehrlein, Freiburg, Germany 8.Dr. Johannes Waltenberger, Maastricht, the Netherlands 9.Dr. Carlos Macaya, Madrid, Spain 10.Dr. Anthony Gershlick, Leicester, UK 11.Pr. Nicholas Peters, London, UK 12.Pr. Tomasz Siminiak, Poznan, Poland 13.Dr. Peter Smits, Rotterdam, the Netherlands SEISMIC Trial Investigators 13 investigative sites, 6 European countries Independent Data Safety & Monitoring Board –J. Tijssen, Chair – Amsterdam, The Netherlands –G. Steg – Paris, France –F. Verheugt – Nijmegen, The Netherlands –H. Wellens – Maastricht, The Netherlands SEISMIC Steering Committee –P.W. Serruys, Chair – Rotterdam, The Netherlands –J. Bartunek – Aalst, Belgium –A. Gershlick – Leicester, UK –N. Peters – London, United Kingdom

9. INCLUSION Criteria Age > 18 and < 75 years old NYHA Class II – III Need for revascularization ruled out within 30 days of screening Optimal pharmacological therapy for > 60 days prior to screening Prior MI > 90 days Placement of ICD > 180 days prior to implant Target region wall thickness of > 5 mm by echocardiography LVEF > 20% and < 45% by MUGA EXCLUSION Criteria MI within 12 weeks of scheduled implant NYHA class I or IV CABG within 3 months or PCI within 6 months of cell implant Any cardiac valve replacement or significant aortic stenosis Heart failure secondary to valvular disease Severe tortuosity of aorta, iliac or femoral arteries Prior angiogenic therapy or myocardial laser therapy End stage renal disease SEISMIC Eligibility Criteria

10. SEISMIC Study Flow 3-M FU 6-M FU Holter ICD SCREENINGINJECTION 1-M FU ICD -3w7d14d21d-6M-4w 0 1M3M6M Holter ICD implant Holter ICD QOL Holter ICD ECG Echo Holter ICD QOL Biopsy Viral ECG QOL Echo MUGA Echo MUGA Holter ICD QOL Echo MUGA QOL comprises Minnesota Living with Heart Failure Questionnaire, NYHA Heart Failure Classification and 6-minute walk test. -2w -1w Holter

11. SEISMIC Baseline Characteristics 6-Month Analysis (n=40) MeanRangeMean Range Age (years)5932-7262 44-75 Years since last MI8.31-217.11-17 Years ICD in place1.91-52.61-5 Race: caucasian (%) 100 % 100 % Prior MI (%) 100 % 100% Male (%)92 % 71 % Prior history of VT (%) 69 % 64 % Diabetes type II (%)31 % 14 % NYHA class III (%)39 % 21 % LVEF (%) 30.9  9.219-5332.6 + 11.2 15-55 TREATMENT (n=26) CONTROL (n=14)

12. SEISMIC Skeletal Myoblasts Harvest and Culture Biopsy Weight (gr)9.1 ± 2.8 Cell harvest (x10 6 )888 ± 319 Cells injected (x10 6 )592 ± 184 Number of injections24 + 7 CD56 staining > 50%100% Volume of cell transplant (mL)11.8 ± 3.7 Number of cells injected based on infarct size; Non-ionic contrast media may be mixed with cells

13. Control Tx Myoblast Tx Probability Freedom from SAE / Death SEISMIC Kaplan Meier Survival Curve for Time to Onset First SAE or Death d5 VT term by ICD d6, d8, d9 VT term by ATP d11 VT term by ICD BB/ Amiodarone/ Flecainide  arrhythmia control 2 wks with status improvement 27-30 ddeterioration CHF death One patient died in the treatment arm (3.8%), no deaths in the control arm.

14. SEISMIC Serious Adverse Events Timing of the episodes of tachyarrhythmia on sequential holter monitoring (no. of patients and no. of episodes in brackets) MyoCell TxControl Tx periproc1/26 (3.8 %, 1 eps) < 1 wk2/26 (7.7 %, 3 eps)1/14 (7.1 %, 1 eps) 1-4 wks2/26 (7.7 %, 3 eps)3/14 (21.4 %, 10 eps) 1-6 mo2/26 (7.7 %, 3 eps)1/14 (7.1 %, 1 eps)

15. SEISMIC NYHA Heart Failure Class Myoblast Therapy Control Therapy N=26N=23N=22N=20 N=14N=9N=12N=13 BL1 mo3 mo6 mo BL1 mo3 mo6 mo

16. SEISMIC MUGA Global LV Ejection Fraction Treatment N=26N=23 Control N=14N=13N=14 30.9 %31.2 % 32.6 %32.5 %

17. SEISMIC +60.3 m + 54.1 -0.2 m ± 177.1 Treatment N=26 N=21 N=19 Control N=14 N=12 N=13 448 m441 m 406 m466 m 6-Minute Walk Test Difference Between Baseline and 6 Months

18. SEISMIC Minnesota Living With Heart Failure QOL Score Baseline3-month6-month N=26N=14N=21N=12N=19N=13

19. 58%94%31%84%57%67%50%56% 42%6%69%16%43%33%50%44% NYHA HF LVEF6MWT Improved or or No Change Worsened control SEISMIC Response to Treatment NYHA HF / 6MWT / MLFQ / LVEF myoblast MLFQ control myoblast control myoblast control myoblast

20. – The SEISMIC trial is a phase II-a, open-label, placebo- controlled, randomized, multi-center study. – Primary Safety Endpoint: In this heart failure population previously fitted with an ICD, myoblast cell therapy was not associated with an increased incidence of arrhythmia, as documented by holter tape and ICD recordings, and appeared to be safe. – Primary Efficacy Endpoint: The MUGA global LVEF remained unchanged, without overall sign of deterioration. Percutaneous Intramyocardial Transplantation of Autologous Myoblasts: BIOHEART SEISMIC Trial

21. – Secondary Efficacy Endpoint: 6-minute walk test showed an improvement not seen in the control group, which was corroborated by a change in NYHA classification, while further deterioration in these parameters was observed in the control group. – However, none of these changes were statistically significant, and may be the result of a placebo effect in the absence of a true blind placebo- control group with sham treatment. – Further investigation in double-blind (sham treatment), placebo-controlled studies to evaluate autologous myoblasts in patients with CHF is warranted (MARVEL, CAUSMIC II). Percutaneous Intramyocardial Transplantation of Autologous Myoblasts: BIOHEART SEISMIC Trial

23. SEISMIC Serial Echocardiographic Analysis of Dimension in the Myoblast Treated Group (n=26) N=22N=15 LVESDLVEDD 54.651.764.464.1

24. 31%84%58%94%50%56% 69%16%42%6%50%44% 6MWTLVEF NYHA HF Improved or or No Change Worsened control SEISMIC Response to Treatment 6 MWT / NYHA HF / LVEF myoblast control myoblast control myoblast

25. 31%84%57%67%50%56% 69%16%43%33%50%44% 6MWT LVEFMLHFQ Improved or or No Change Worsened control SEISMIC Response to Treatment – 6 MWT / QoL / LVEF myoblast control myoblast control myoblast

26. Secondary efficacy end point: 6 min walking test shows an improvement not seen in the control group, corroborated by a change in the NYHA classification in the cell-treated group, while a further deterioration was seen in the control group. However, none of these changes were statistically significant, and may be the result of a placebo effect in the absence of a true blind placebo control group with sham treatment. Percutaneous Intramyocardial Transplantation of Autologous Myoblasts: BIOHEART SEISMIC Trial

27. However, these clinical benefits could not be substantiated by echocardiography and MUGA LVEF Placebo effect ? Appropriate surrogate end point markers ? (regional wall motion by MRI/ TTE, PV loop analysis) Technical issues Is this the correct target population for cell therapy per se? arrhythmia prone, irreversible CMP Validity of efficacy end points Placebo effect is a confounding factor, therefore double blind, placebo-control with sham treatment, adequately powered studies are warranted (Causmic II, Marvel) Percutaneous Intramyocardial Transplantation of Autologous Myoblasts: BIOHEART SEISMIC Trial

28. SEISMIC Patient Selection Primary Inclusion Criteria: –Prior MI > 90 days with region of myocardial dysfunction involving the anterior, lateral, posterior or inferior walls –Placement of ICD 6 months prior to study entry –LVEF at screening of ≥ 20% ≤ 45% (by MUGA scan) –New York Heart Association (NYHA) Class II or III –Patients on optimal pharmacological therapy for at least 2 months prior to study entry –Need or feasibility for re-vascularization has been ruled out within 30 days of screening –Minimum myocardial wall thickness of 5mm –Age ≥ 18 and ≤ 75 years old

29. SEISMIC Patient Selection Primary Exclusion Criteria: –CABG within 180 days OR PCI within 90 days prior to scheduled MyoCell™ implantation –Aortic valve replacement –Exposure to any investigational drug or procedure within 1 month prior to study entry or enrolled in any concurrent study that could confound the data –ICDs implanted less than 180 days or reprogrammed less than 90 days prior to cellular implantation –Patients fitted with Bi-V pacers –Patients unable to take anti-arrhythmic medications –Evidence of left ventricular mural thrombus

30. SEISMIC Study Flow Days 1-2 Days 7-8 Days 14-15 Days 21-22 Day 28(±2) Day 35(Implantation) 30 Days (±2 days) post implantation 90 Days (±2 days) post implantation 180 Days (±2 days) post implantation Visit 1 Screening ICF Biopsy Request Form HX/Med Review PE ECG NYHA Class 6-min walk Min QOL MUGA DSE TDI ICD Review Amiodarone Pivitol Core Lab · Viral Screen · Serum Chemistry · Hematology · Coagulants Local Lab · Urinalysis · CardiacPanel Screening 24 hr Holter Monitoring # 1 Screening 24 hr Holter Monitoring # 2 Visit2 Biopsy/Assessment HX/Med Review PE AE Assessment ECG ICD Review Amiodarone Cont. HolterMonitoringWeekly Pivitol · Serum Chem · Hematology · Coags Local Lab · Urinalysis · Cardiac Panel Treatment Group Muscle Biopsy Visit4 1 Month Follow-up HX/Med Review PE ECG NYHA Class 6-min walk Min QOL ICD Review HolterMonitoring Monthly amiodarone D/C’d Pivitol · Serum Chem · Hematology · Coags Local Lab · Urinalysis · Cardiac Panel Visit6 6 Month Follow-up HX/Med Review PE ECG NYHA Class 6-min walk Min QOL MUGA DSE TDI ICD Review Pivitol · Serum Chem · Hematology · Coags Local Lab · Urinalysis · Cardiac Panel Screening 24 hr Holter Monitoring # 3 Screening 24 hr Holter Monitoring # 4 Randomization Visit3 Treatment - Implantation Pre-Procedure PE AE Assessment ECG ICD Review Resting Echo (prior) ICD Review Local Lab · Cardiac Panel(6 hrs prior) Post-Procedure Telemetry(8 hrs inhospital) Local Lab · Cardiac Panel (6 hrs post) Resting ECHO (6 hrs post) 72 hrHolter Monitoring Discharge Instructions amiodaroneCont. Frequent Telephone Contacts ICD Review Weekly Holter Monitoring Weekly Visit3 Control- Assessment HX/Med Review PE AE Assessment ECG ICD Review amiodaroneCont. 72 hr Holter Monitoring HolterMonitoringWeekly Pivitol · Serum Chem · Hematology · Coags Local Lab · Urinalysis · Cardiac Panel Visit5 3 Month Follow-up HX/Med Review PE ECG NYHA Class 6-min walk Min QOL MUGA DSE TDI ICD Review HolterMonitoring Monthly Pivitol · Serum Chem · Hematology · Coags Local Lab · Urinalysis · Cardiac Panel Visit 2a Re-Biopsy (if needed) Vital Signs AE Assessment ICD Review Amiodarone Cont. Muscle Biopsy

31. SEISMIC Committees Independent Data Safety & Monitoring Board –J. Tijssen, Chair – Amsterdam, The Netherlands –G. Steg – Paris, France –F. Verheugt – Nijmegen, The Netherlands –H. Wellens, EP – Maastricht, The Netherlands SEISMIC Steering Committee –P.W. Serruys, Chair – Rotterdam, The Netherlands –J. Bartunek – Aalst, Belgium –A. Gershlick – Leicester, UK –N. Peters, EP – London, United Kingdom

32. Biopsy Culture Delivery SEISMIC MyoCell™ Production

33. MyoCell™ Specifications Skeletal myoblasts suspended in organ transport media 30 ml bag is sterilized prior to filling with cells and handled aseptically thereafter Concentration: 25 million cells /.50 cc Temperature controlled delivery Cell viability: 4-days from harvest

34. MyoCath™ Specifications Sheath Compatibility – 8f Usable Catheter Length – 115 cm Core Needle Diameter – 25 gauge Core Needle “dead space” – 0.5cc Adjustable Needle Length 3mm – 6mm Syringe Compatibility – 1cc Luer Lock Curve Size – Medium and Large

35. SEISMIC Injection Guide Non-ionic contrast media may be mixed with the cells Confirm accuracy of injections under fluoroscopy Contrast media approved for use: Visipaque®, Optiray® Create grid pattern with 1 cm spacing

36. Apical Basal A B Epi EndoInjections Cell Implant Procedure (From Animal Training)

37. SEISMIC Enrollment By Site

38. SEISMIC 6 Minute Walk Test N=26 N=14N=21N=12N=19N=13 Treatment change BL – 6 months: 60.3 m + 54.1 Control change BL – 6 months: -0.2 m + 177.1

39. SEISMIC Dobutamine Stress Echocardiography N=22N=7N=15N=4N=13N=6 LVESD LVEDD N=22N=7N=15N=4N=15N=6

40. SEISMIC Serial echocardiographic analysis of dimension in the myoblast treated group (n=26) N=22N=15 N=13 N=22N=15 LVESD LVEDD

41. SEISMIC Dobutamine Stress Echocardiography – LVEDD Treatment N=22N=15 Control N=7N=4N=6

42. SEISMIC change of NYHA heart failure class distribution 0 - 1 mo0 - 3 mo0 - 6 mo0 - 1 mo0 - 3 mo0 - 6 mo N= Myoblast therapyControl therapy

43. SEISMIC MUGA global LV ejection fraction N=26N=14N=23N=13N=23N=14

44. SEISMIC Dobutamine Stress Echocardiography – LVESD Control N=7N=4N=6 Treatment N=22N=15 N=13

45. SEISMIC Serious Adverse Events Timing of the episodes of tachyarrhythmia on sequential holter monitoring (no. of patients and no. of episodes in brackets) MyoCell TxControl Tx periproc1/26 (3.8 %, 1 eps) < 1 wk2/26 (7.7 %, 3 eps)1/16 (6.3 %, 1 eps) 1-4 wks2/26 (7.7 %, 3 eps)3/16 (18.8 %, 10 eps) 1-6 mo2/26 (7.7 %, 3 eps)1/16 (6.3 %, 1 eps) Relation between all adverse event and study therapy (no of episodes) MyoCell TxControl Tx Possible3/10 (30.0 %) Probable7/10 (70.0 %) Definite 0/10 ( 0.0 %) * Peri-procedural arrhythmia were not adjudicated as (S)AE

46. SEISMIC Minnesota Living With Heart Failure QOL Score Control N=14 Treatment N=25 N=23 N=24

47. Seismic A Phase IIa, Multi-Center, Open Label, 23%84%57%67%50%30% 8%0%0%0%0%26% 69%16%43%33%50%44% 6MWT LVEFMLHFQ Improved No Change Worsened Treated Pts. BL:6-Months Control Pts. BL:6-Months Treated Pts. BL:6-Months Control Pts. BL:6-Months Treated Pts. BL:6-Months Control Pts. BL:6-Months

48. Bioheart Clinical Experience MYOHEART US Phase I Completed 2007 SEISMIC EU Phase II-a Completed 2008 FIM EU Phase I Completed 2002 005/006 EU Phase I/II Completed 2003 BH-TVI* Single-Site Registry Discontinued* * 3 patients enrolled. Trial discontinued following acquisition of TransVascular inc. by Medtronic Inc. n = 5 n = 3n = 15 n = 20n = 40

49. Overall Objective: To assess the safety and efficacy of MYOCELL™ therapy on myocardial function in CHF patients post MI(s). Primary Safety Endpoint –Defined Serious Adverse Events (SAEs) at 3 & 6 mos Bioheart EU Phase II-a Trial – SEISMIC Secondary Safety Endpoints –Holter monitoring, 12-lead ECG data, frequency of ventricular arrhythmias –Safety of the use of the MyoCath™ injection catheter by Adverse Event (AE) assessment –Number and mean length of stay for hospitalizations fatal or life-threatening events prolonged or required hospitalization sustained arrhythmia for > 30 seconds documented worsening of congestive heart failure Resulting in permanent impairment or surgical intervention to preclude permanent impairment of a body function –Medical and scientific judgment by the DSMB committee was exercised when classifying events as serious