CELL THERAPY FOR THE

TREATEMENT OF SEVERE
HEART DISEASE
Using
Intracoronary & Intramyocardial
Injected ACPs
Clinical Trial in Angina pectoris
Patients
To determine the safety and
efficacy of intracoronary
injection of autologous
ACPs in relieving symptoms
of angina pectoris in
patients on maximal medical
therapy
First ACPs injection on August 2004
 Clinical Trial Safety Results
24 Patients - NO GVHD
No serious adverse events were attributed to the
injected cells
• 1 Death (unrelated)
• Very few adverse effects
• Rare events of transient arrhythmia (related to
catheterization)
Deaths Serious Adverse Events Adverse Events

• No
1 evidence
3 in of tumoregenesis
3 patients 10 in 7 patients
MI of an •Transient ventricular •Elevated Erythrocyte Sedimentation Rate
unrelated fibrillation during cell (2)
artery administration procedure (1) •Chest pain during cell administration (1)
[Stent •Transient ventricular •Hypoglycemia (1)
blockage] fibrillation during follow up •Upper respiratory tract infection (1)
procedure of catheterization •Oral paresthesia (1)
at 6 months after cell •Urticaria (2)
administration (2) •Hematoma at puncture site
•Leg Pain (1)
 Clinical Trial
3 and 6 months follow-up results
Angina Pectoris re
Patients fo
Be
Objective
parameters
Perfusion of heart
muscle
Work load capacity

Mostr of the effect

fte
achieved by 3
A
months after
treatment
 Clinical Trial
3 and 6 months follow-up results
Canadian Cardiovascular Society (CCS)
Angina Pectoris Patients Grading Scale
3

Subjective parameters P<0.001*

CCS (Angina score)

CCS Score
2

Exercise capacity – 6 minute walking P<0.001* P=0.426

test 1

2.2 1.0 1.1

Clinical Trial 1 Year Follow-up 0

Baseline 3 Months 6 Months

11 Patients Six Minutes Walking Test

No serious adverse events
460
P<0.001*
440

9/11 No chest pain at all

Distance (meters)
420

2/11 Rare episodes of chest pain 400 P=0.0018* P=0.05

380
1/11 PTCA 360

340

320

338 410 423

300

Baseline 3 Months 6 Months

 > 300 Out-of-Study Patients
Categorized by Procedures

350

300

250
317
200
Number

150

174
100
134

50
9

0
Procedures
Intramyocardial Intracoronary PAD Total
 Medical History
200 71% Intracoronary Intramyocardial
66%
180
16% 57%
160
(43) 32.5%
51%
(87)
140 46%
11% 24%
120 (28)
10% (63)
38%
Number

(27)
100 33%
16%
80 (43)
50%
(134) 22%
60 38.5% 40%
(60) 36% 14%
(103) (107) 33%
(95) (89)
40 22% 4%(11)
(59)
20 11% 10%
(28) (27)
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Patients also had

N
Patient Gender

Fem ale
10%

Male
90%
Patient Age Distribution
90-94 20-29
0.4% 1.1%

30-39
80-89 4%
6% 40-49
7%

70-79
25% 50-59
24%

60-69
33%
 Country of Origin
Singapore, U.A.E., 1%
1%
Canada, 1%

Myanmar, 2% Others
India, 2% 7%
Australia, 2%

Thailand
5%

U.S.A.
79%

Others : Azerbaijan, China, Germany, Indonesia, Israel, New Zealand, Abudhabi, England, Philippine, Italy,
Mexico, Netherland, Parkistan, and Span
 Results by
Treatment and Diagnosis
 NYHA, CCS score
Intracoronary delivery
(A) (B) New York Heart
Canadian Cardiovascular
Society (CCS), N = 87 Association (NYHA), N = 92
3
3
P=0.000 P=0.000*
2.5 * 2.5

2 2

NYHA Scale
CCS Scale

1.5 1.5
2.58 2.69
1 1 2.02
1.64
0.5 0.5

0 0
Baseline 2-4 Months Baseline 2-4 Months

Statistical Method : Wilcoxon Signed Ranks Test

* Significant improvement (p<0.001)
 Ejection Fraction
Intracoronary delivery
(E) Stress EF(%) by Tc 99m
Sesta MIBI / SPECT
50
P=0.046
45
40
35

EF% 30
25
46
20
35
15
10
5
0
Baseline 2-4 Months

Statistical Method : Paired T-test

* Patients number from whom tests results were sent by the physicians, N=12
 Result
Intramyocardial delivery
(A) NYHA Classification (B) Brain Natriuretic Peptide (BNP) (C) 6 Minute Walking Test
N = 90 N = 22 N = 22
3 4000 800
P=0.000* P=0.020 P=0.166
3500 700
2.5
3000 600
2

BNP (pg/ml)
2500 500
NYHA Scale

Meter(s)
1.5 2000 400
2.7 751
3,384
1500 300
1 1.9
1000 200
1,542 357
0.5
500 100

0 0 0
Baseline 2-4 Months Baseline 2-4 Months Baseline 2-4 Months

Statistical Method : Wilcoxon Signed Ranks Test Statistical Method : Paired T-test
* Significant improvement (p<0.001) * Significant improvement (p<0.02)
 Ischemic CHF
(A) NYHA Classification ( B) R e s t EF(%) b y Ec h o c a r d io g r a p h y, (C) Rest EF(% ) by C-MRI/
N = 76 N = 54 SPECT/ Sesta MIBI, N = 13
3 40
P=0.000* 40 P=0.731
P =0.35 1
35
2.5 35
30 30
2
25 25
NYHA Scale

35

EF(%)

EF(%)
1.5 2.6 20 3 1 .4 20
15 3 0 .3 15
33.4
1 2.0
10 10
0.5 5
5
0
0 0
Baseline 2-6 Months
B a s e lin e 2 - 6 M o n th s Baseline 2-6 Months

Statistical Method : Wilcoxon Signed Ranks Test Statistical Method : Paired T-test
* Significant improvement (p<0.001)
 Ischemic CHF
(D) BNP (pg/ml) (E) 6 Minute Walking Test
N = 10 N = 10
3000 1400
P=0.116 P=0.163
2500 1200

1000
2000
BNP (pg/ml)

Meter(s)
800
1500
2,601 600 1,247
1000
400

500 1,105
200 361

0 0
Baseline 2-6 Months Baseline 2-6 Months

Statistical Method : Paired T-test

 Non-ischemic Cardiomyopathy
(C) NY HA C las s ific atio n (D) BNP (pg/ml) (E) 6 M inute Walking T est
N = 76 N = 13 N = 12
3 4500 1200
P=0.000* P=0.015 P=0.246
4000
2.5 1000
3500
2 3000 800

BNP (pg/ml)
NYHA Scale

2500

Meter(s)
1.5 2.6 600
2000 3,870 972
1 1.9 1500 400
1000
0.5 200 361
500 1,153
0 0 0
Baseline 2-6 Months Baseline 2-6 Months Bas eline 2-6 Months

Statistical Method : Wilcoxon Signed Ranks Test Statistical Method : Paired T-test

* Significant improvement (p<0.001)

 Clinical Experience
SF-36 V2TM Health Survey
Comparison between Pre-SC Tx and 3-6 Months Post-SC
100 (N=96)
Tx Pre-SC Tx 3-6 Months Post SC Tx

77.75
80 74.58
Definition 69.42
72.14
69.41

PF Physical Function 60.91

64.24

57.58 57.96 58.55

60
0-100 Score

52.04 52.45
RP Role Physical
BP Bodily Pain 36.15 36.25
40 35.31
32.1
GH General Health
VT Vitality
20
SF Social Function
RE Role Emotional
0
MH Mental Health PF RP BP GH VT SF RE MH

SF-36v2TM Health Survey@1996,2000 by Quality Metric Incorporated and Medical Outcomes Trust-All Rights Reserved
SF-36 is a registered trademark of Medical Outcomes Trust
(SF-36 v2 Standard ,US Version 2.0)
 Clinical Experience
SF-36 V2TM Health Survey
Comparison between Pre-SC Tx and 1 Year Post-SC Tx
100
Pre-SC Tx 1 Year Post SC Tx (N=46)

77.54
Definition 80 75.22
71.2
67.04
PF Physical Function 64.22
67.78

60.33 61.78
RP Role Physical 60 54.89 55.57
54.07
50.41
0-100 Score

BP Bodily Pain
42.72 41.58 43.42
39.17
GH General Health
40
VT Vitality
SF Social Function
20
RE Role Emotional
MH Mental Health
0
PF RP BP GH VT SF RE MH

SF-36v2TM Health Survey@1996,2000 by Quality Metric Incorporated and Medical Outcomes Trust-All Rights Reserved
SF-36 is a registered trademark of Medical Outcomes Trust
(SF-36 v2 Standard ,US Version 2.0)
 Safety
> 300 Out-of-study Patients
Death
Average follow up period = 5.5+1 month Death
Range follow up period = 1-24 month
9%
Intracoronary (10):
- 3 Cardiac arrest

- 3 Heart Failure

- 1 Septic Shock S/P pneumonia

- 1 Ac. Renal shut down with MOF Alive

91%
- 1 Aneurysm with metastasis pancreas cancer

- 1 Suicide

Intramyocardial (19):
- 7 Cardiac arrest

- 3 Heart Failure

- 6 Unknown cause (Post SC Tx >6months)

- 2 Ac. Renal failure

- 1 End stage CA

• No deaths or SAEs can be directly attributed to the stem cells injection

• Completed absence of tumoregenesis evidence.
• No GVHD
 Safety
> 300 Out-of-study Patients
Serious Adverse Events (SAEs)
Intracoronary Intramyocardial
• Recurrent CHF (12) • Temporary recurrent PVCs (6)

• Priaprism (1) • Ventricular Fibrillation (twice in 1 pt)

• Pneumonia/ Pleural effusion (5) • Ventricular Tachycardia (3)

• Repeated MI (2) • Atrial Fibrillation (5)

• Defibrillator implantation (2) • Unspecified Arrhythmia (1)

• Ac. Renal failure (1) • Cardiac arrest (twice in 1 pt)

• GI Bleeding (1) • Recurrent CHF (10)

• Hemodialysis (3) • Peumonia/ Pleural effusion (6)

• Heart transplantation (2) • Defibrillator misfiring (2)

• Embolic stroke (1) • Ac.Renal failure (2)

• Bronchitis (1) • Episode of TIA (S/P gall bladder) (1)

• Influenza (1) • Gout attack (1)

• Hyperglycemia (1) • Hemodialysis (5)

• Hyponatremia (1) • Influenza (1)

• Prolong hospitalization (2)

• Pericardial effusion (1)

34 (10.7%) 48 (15.1%)
 Conclusion
Intracoronary & Intramyocardial injection

• Intracoronary & Intramyocardial ACPs implantation is safe and

effective.

• Significant improvement of the CCS, NYHA and the quality of

life in both intracoronary and intramyocardial approach.

• The CCS, NYHA, BNP, 6MW and the LVEF% function had
improved in Ischemic CHF, CHF with Angina, and Non-
ischemic cardiomyopathy
 Clinical Experience
Peripheral Arterial Disease
First patient treated on April 11,2006
 Clinical Experience
Diabetic PAD Treatment
Injection Two days later
 Clinical Trial - PAD
Pre-Operation Day 17 Day 33 Day 90

Pre- 5
Operation Months