MYOHEART US Phase I Study Interim Analysis

1
MYOHEART US Phase I StudyInterim Analysis
January 17-19, 2007
Warren Sherman, M.D. Director,
Cell-Based Endovascular Therapies
2
MYOHEART Study Flow
First Cohort (n5)
2 injections (.25 cc)
25 x 10
cells
6
30
-
Day Safety
Evaluation
Second Cohort (n5)
6 injections (.25 cc)
75 x 10
cells
6
30
-
Day Safety
Evaluation
Third Cohort (n5)
18 injections (.25 cc)
225 x 10
cells
6
30
-
Day Safety
Evaluation
Fourth Cohort (n5)
27 injections (.50 cc)
675 x 10
cells
6
Clinical Sites Columbia Presbyterian, Cleveland
Clinic, Mayo Clinic, Minneapolis Heart, St.
Josephs / ACRI Core Lab Gentiae Clinical
Research
3
MYOHEART Objectives

• To assess the safety and feasibility of MyoCell
  (autologous myoblasts) following implantation
  into myocardial tissue of CHF subjects who
  experienced prior MI (gt 12 weeks),
• To assess the safety and feasibility of the
  MyoCath transendocardial needle-injection
  catheter as a system for delivering MyoCell into
  myocardial tissue, and
• To assess the effect on myocardial structure and
  function of MyoCath mediated MyoCell implantation.

4
MYOHEART Endpoints

• Safety Incidence and nature of serious
  adverse events (SAEs) up to 12 months
  (includes events related to vascular,
  cardiac, arrhythmic or device malfunction)
• Efficacy Changes from baseline, 1, 3, 6 and 12
  month intervals of regional and global LV
  wall thickness and function
• Independent database management performed by
  Gentiae Clinical Research. Responsibilities
  include core laboratory analysis (48-hour Holter,
  MUGA, PET Scan, Echocardiography and ECG
  analysis), adverse event reporting, case report
  form database, data management and data safety
  monitoring board.

5
MYOHEART Eligibility Criteria

• INCLUSION Criteria
• Prior MI involving anterior, lateral, posterior
  or inferior walls gt 12 weeks old at time of
  implant
• Patients with prior placement of an ICD gt 30 days
  prior to implant
• NYHA Class II III
• Age gt 30 and lt 80 years old
• Need for revascularization ruled out by coronary
  angiogram or noninvasive stress test within 6
  months of screening
• Target region wall thickness of gt 6 mm by
  echocardiography
• LVEF gt 20 and lt 40 by MUGA at screening
• Ability to walk at least 300 meters during
  6-minute walk test

• EXCLUSION Criteria
• MI within 12 weeks of scheduled implant
• NYHA class I or IV
• CABG within 3 months or PCI within 6 months of
  implant
• Any cardiac valve replacement
• Heart failure secondary to valvular disease
• Aortic stenosis greater than mild degree
• Severe tortuosity of aorta, iliac or femoral
  arteries
• Prior angiogenic therapy or myocardial laser
  therapy
• Active infectious disease
• Pregnant females

6
MYOHEART Study Flow
- ECG
Holter
Holter
Holter
Holter
Holter
Holter
- Holter
ICD
ICD
ICD
ICD
ICD
ICD
-ICD
QOL
QOL
QOL
QOL
QOL
ECG
ICD
Echo
Viral / CP
Echo
Echo
Echo
MUGA
MUGA
MUGA
implant
MUGA
PET
Echo
PET
Biopsy
-3w
1d
3d
7d
-1M
-4w
0
1M
3M
12M
6M
3 MFup
6MFup
12 MFup
SCREENING
INJECTION
1 MFup
ICD
7
MYOHEART Baseline Profile
Cohort 1
Cohort 2 Cohort 3
Cohort 4 ALL TOTAL
(25x106)
(75x106) (225x
106) (675x106)
Subjects
5 5
5 5
20 Age (yr)
Mean (SD) 51.4 (8.6)
63.4 (10.9) 61.0 (9.5)
57.0 (8.0) 58.3
(9.8) Median (Min, Max) 48.0
(44, 65) 59.0 (53, 77)
60.0 (47, 73) 57.0 (49, 65)
58.0 (44, 77)


Sex, Male () 5/5 (100)
5/5 (100) 5/5
(100) 5/5 (100)
20/20 (100) Race ()


Caucasian 3/5
(60.0) 5/5 (100)
4/5 (80.0) 4/5 (80.0)
16/20 (80.0) Black
0/5 (0)
0/5 (0) 0/5 (0)
1/5 (20.0) 1/20 (5.0)
Asian 1/5
(20.0) 0/5 (0)
0/5 (0) 0/5 (0)
1/20 (5.0) Hispanic
1/5 (20.0)
0/5 (0) 1/5 (20.0)
0/5 (0) 2/20 (10.0)
Medical History

Diabetes
3/5 (60.0)
1/5 (20.0) 1/5 (20.0)
3/5 (60.0) 8/20 (40.0)
Stroke
0/5 (0) 0/5 (0)
0/5 (0) 1/5 (20.0)
1/20 (5.0) Arrhythmia
3/5 (60.0)
1/5 (20.0) 4/5 (80.0)
2/5 (40.0) 10/20 (50.0)
NYHA Class

Class II
4/5 (80.0)
3/5 (60.0) 1/5 (20.0)
3/5 (60.0) 11/20 (55.0)
Class III 1/5
(20.0) 2/5 (40.0)
4/5 (80.0) 2/5 (40.0)
9/20 (45.0) LVEF MUGA () 5
5 5 2
17 Mean (SD) 22.4 (2.0)
27.0 (8.1)
22.4 (2.1) 24.5 (6.3)
24.0 (5.0) Median (Min, Max)
23.0 (20, 25) 28.0 (14, 36)
22.0 (22, 28) 24.5 (20, 29)
23.0 (14, 36)
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MYOHEART Cell Product and Delivery
9
MYOHEART Clinical Outcomes

Cohort I
Cohort II Cohort III
Cohort IV
(N 5)
(N 5)
(N 5) (N
5)
Pts Events
Pts Events Pts Events
Pts Events Overall
2/5 5
1/5 3
3/5 4 2/5
4 Death 0 0
1/5 1 0
0 1/5 1 Cardiac
disorders 2/5 2
1/5 2
1/5 1 2/5
3 Progressive HF
0 0 0
0 0 0
1/5 1 NSVT
1/5 1
0 0
0 0
1/5 1 Ventricular arrhythmia
0 0 1/5
2 1/5 1
1/5 1 Atrial
arrhythmia 1/5 1
0 0
0 0 0
0 Incision site Hemorrhage 1/5
1 0 0
0 0
0 0 Skeletal Tissue
Disorders 1/5 2
0 0 0
0 0 0


Arthralgia
1/5 1
0 0 0
0 0 0
Osteoarthritis
1/5 1 0
0 0 0
0 0 Nervous System
Disorders 0 0
0 0 1/5
1 0 0
Dizziness
0 0 0
0 1/5 1
0 0 Respiratory,
Thoracic Disorders 0 0
0 0 1/5
2 0 0


Pleural effusion
0 0
0 0
1/5 2 0
0
10
MYOHEART Arrhythmia

• 6 patients experienced arrhythmias
• Adjudicated by Investigator as Not Related to
  Therapy
• Patient 506 intermittent VT 278 days
  post-procedure resolved with single ICD firing.
  Full resolution.
• Patient 902 atrial fibrillation with single ICD
  firing. Firing deemed inappropriate, anti-
  atrial fibrillation medication provided with full
  resolution.
• Adjudicated by Investigator as Possibly Related
  to Therapy
• Patient 701 2 ICD firings at days 52 and 72 post
  procedure. Second event of sustained VT not
  resolved and patient expired.
• Patient 911 runs of NSVT through first week
  post-procedure. No ICD firing. Amiodarone
  provided, full resolution.
• Patient 912 runs of NSVT through first two weeks
  post-procedure. Amiodarone provided, full
  resolution. No ICD firing.
• Patient 914 multiple ICD firings 7 days post
  implant. Patient hospitalized, provided with
  Amiodarone, arrhythmias resolved. Patient
  expired approximately 5 months post-procedure due
  to progressive heart failure.

11
MYOHEART MUGA
N17
N14
N14
N10
N17
N14
N14
N10
MEAN ()
MEAN ()
26.9
26.4
26.1
24.0
N/A
N/A
p n/s
12
MYOHEART 6 minute walk
Absolute Improvement (m)
Relative Improvement ()
22
20
10
6
Cohort 1
Cohort 2
Cohort 3
Cohort 4
N5
N4
N5
N1
N5
N4
N5
N1
p n/s
13
MYOHEART QOL
21 QOL Questions Each Question Relates to Degree
HF Limits the Patient Physically and
Emotionally. Range 0 (no impact) 5 (highest
impact). Lower is Better.
N18
N16
N12
N7
N18
N16
N12
N7
MLHFQ Score
MLHFQ Score
54.8
43.1
42.0
29.3
N/A
N/A
p n/s
14
What have we learned?

• Safety strongly suggested in this small study
• Clinical efficacy suggested re. QOL, exercise
  capacity
• Learning curves inherent in an early phase trial
• Optimization of cell processing
• Modifications Injection technique

15
Subject 19 Benefit of cell labeling
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What have we learned?

• In combination with results from other
  non-randomized and randomized (MAGIC, SEISMIC) we
  have sufficient justification to proceed to a
  pivotal, clinical end-point trial
• Randomized, double-blinded, placebo-controlled
  study
• Unique design features
• Serial injections 2 sessions, 4 weeks apart
• Cross-over
• First dose placebo controlled
• Second dose both groups treated

17
Contributors

• Investigators
• Steve Ellis
• Tim Henry
• Nic Chronos
• David Holmes

• Bioheart
• Richard Spencer
• Howard Leonhardt
• Doug Owens

18
MYOHEART US Phase I StudyInterim Analysis
January 17-19, 2007
Warren Sherman, M.D. Director,
Cell-Based Endovascular Therapies