Mesoblast Limited · ASX:MSB
Mesoblast — American Heart Association Scientific Session 2011
24 slides from Mesoblast's conference presentation, Nov 15, 2011
Slide 1: Phase II Dose-Escalation Study of Allogeneic MPCs in Heart Failure
A Phase II Dose-Escalation Study of Allogeneic Mesenchymal Precursor For personal use only Cells in Patients With Ischemic and Nonischemic Heart Failure American Heart Association Scientific Session 2011 November 14, Orlando, Florida Emerson C. Perin MD, PhD
Slide 2: Study Sites, Investigators and Enrollment
Study Site PI Enrollment For personal use only Minneapolis Heart Institute Timothy Henry 20 Mercy Gilbert Medical Center Nabil Dib 19 Texas Heart Institute Emerson Perin 12 Univ. of California, San Diego Anthony DeMaria 5 University of Pittsburgh Oscar Marroquin 3 Swedish Medical Center Paul Huang 1
Slide 3: Background
Background 1. Most clinical trials in cell therapy have used autologous adult For personal use only stem cells in patients with chronic ischemic cardiomyopathy or refractory angina. 2. Autologous cell therapy may be limited by variability in cell quality due to host factors such as age and comorbidi
Slide 4: Mesenchymal Precursor Cells (MPCs)
Mesenchymal Precursor Cells (MPCs) Heart For personal use only muscle Cardiovascular Bone marrow + disease STRO-3+ antibody Blood therapies vessels Magnetic beads Pancreas Diabetes, immunologic/ MPC highly expandable inflammatory Immune system conditions Bone Culture- Orthopedic Isolated cells expan
Slide 5: Major Inclusion and Exclusion Criteria: Inclusion
Major Inclusion and Exclusion Criteria For personal use only Inclusion Criteria • NYHA II-IV • Age between 20 and 80 years • Cardiomyopathy of ischemic or non-ischemic etiology • LVEF 40% (Echo) • Not amenable to either CABG or PCI (CAD patients) • Maximal medical therapy • LV wall thickness ≥ 8 m
Slide 6: Major Inclusion and Exclusion Criteria: Exclusion
Major Inclusion and Exclusion Criteria For personal use only Exclusion Criteria • Atrial fibrillation, LV thrombus, severe AS • Stroke within 3 months of enrollment • Presence of bleeding diathesis • History of malignancy within 3 years • MI within 30 days, ACS, cardiogenic shock • ICD discharge wit
Slide 7: Study Design
Study Design Eligible n=151 Excluded (n=91) •Did not meet inclusion criteria (n=63) For personal use only •Refused to participate (n=6) •Other (n=22) Enrollment n=60 Treatment 25M MPCs 3:1 n=15 n=20 Aug 2008 - Dec 2008 Control n=5 Safety F/U up to 3y Treatment n=15 NYHA class, 75M MPCs 3:1 Echocardi
Slide 8: Study Design
Study Design Eligible n=151 Excluded (n=91) •Did not meet inclusion criteria (n=63) For personal use only •Refused to participate (n=6) •Other (n=22) Enrollment n=60 Treatment Ischemic 25M MPCs 3:1 n=15 n=15 n=20 Aug 2008 - Dec 2008 Control Ischemic n=5 n=2 Safety F/U up to 3y Treatment Ischemic n=1
Slide 9: Demographic and Baseline Characteristics
Demographic and Baseline Characteristics Pooled MPC For personal use only Control 25M MPCs 75M MPCs 150M MPCs Treatment (n=15) (n=15) (n=15) (n=15) (n=45) Age (years) 62.7 (11.2) 62.2 (10.3) 60.1 (8.8) 63.9 (11.5) 62.7 (10.8) Female 4 (26.7) 1 (2.2) * 0 0 1 (6.7) Previous PCI 10 (66.7) 33 (73.3) 12
Slide 10: Immunologic Monitoring Methods
Immunologic Monitoring Methods For personal use only • HLA antigens of the MPC were identified by serologic methods. • MPC HLA alloantigens could be immunogenic in recipients; therefore, we evaluated the antibody and cellular immune responsiveness of patients entered into the study. • Antibody speci
Slide 11: Immunologic Monitoring Results
For personal use only Immunologic Monitoring Results Donor-Specific Anti-HLA Antibody Response 6 of 45 (13%) MPC-treated patients developed DSA. Anti-HLA antibodies produced transiently (< 1 month): • 4 of 45 (9%) total MPC-treated Anti-HLA antibodies persisting > 1 month: • 2 of 45 (4%) total MPC-t
Slide 12: Changes in LV Ejection Fraction
For personal use only Changes in LV Ejection Fraction P=0.184 P=0.188 P=0.704 n=15 n=43 n=13 n=44 n=14 n=42 %
Slide 13: Changes in LV Ejection Fraction
Changes in LV Ejection Fraction 16 14 P=0.925 For personal use only P=0.638 12 P=0.008 3 months 10 P=0.184 P=0.188 P=0.704 8 n=15 n=14 n=14 n=15 % n=1 n=4 n=1 n=4 n=1 n=4 % 6 5 3 3 4 4 2 4 7 2 0 -0.2 -1.9 -1.9 -2 Control 25M 75M 150M -4 16 16 14 P=0.273 14 P=0.469 12 P=0.472 12 P=0.672 P=0.232 P=0.3
Slide 14: Changes in LV End Systolic Volume
For personal use only Changes in LV End Systolic Volume P=0.413 P=0.151 P=0.764 n=14 n=42 n=12 n=43 n=13 n=41 ml
Slide 15: Changes in LV End Systolic Volume
Changes in LV End Systolic Volume P=0.964 For personal usemlonly P=0.646 P=0.413 P=0.151 P=0.764 P=0.070 3 months n=14 n=42 n=12 n=43 n=13 n=41 n=14 n=14 n=13 n=15 ml P=0.015 P=0.126 P=0.156 P=0.664 P=0.809 P=0.394 6 months 12 months n=12 n=15 n=13 n=15 n=13 n=14 n=13 n=14 ml ml
Slide 16: Delta 6-minute Walk
For personal use only Delta 6-minute Walk P=0.181 P=0.723 P=0.227 n=14 n=43 n=13 n=44 n=13 n=42 m
Slide 17: Delta 6-minute Walk
Delta 6-minute Walk P=0.241 For personal usemonly P=0.057 P=0.181 P=0.723 P=0.227 P=0.600 3 months n=14 n=43 n=13 n=44 n=13 n=42 n=14 n=14 n=13 n=15 m P=0.329 P=0.062 P=0.208 P=0.920 P=0.288 P=0.323 6 months 12 months n=13 n=14 n=15 n=15 n=13 n=14 n=14 n=14 ml m
Slide 18: MACE Free Survival: All Subjects
MACE Free Survival All Subjects For personal use only 100 MACE-Free Survival Probability 80 MPC 60 Control 40 20 Log-rank Log RankPP-value value=0.036 = 0.036 0 0 10 20 30 40 TimeTo Time to MACE MACE (months) (Months) MACE: Cardiac Death, Revascularization, MI
Slide 19: MACE Free Survival: Ischemic Subjects
MACE Free Survival Ischemic Subjects For personal use only 100 MACE-Free Survival Probability 80 MPC 60 Control 40 20 P-value = 0.024 Log-rank P value = 0.024 0 0 10 20 30 40 Time toToMACE MACE(months) (Months) MACE: Cardiac Death, Revascularization, MI
Slide 20: Cardiac Death Free Survival: All Subjects
Cardiac Death Free Survival All Subjects For personal use only 100 Cardiac Survival Probability 80 MPC 60 Control 40 20 Log-rank P value = 0.020 Log Rank P-value = 0.020 0 0 10 20 30 40 Time Timeto Cardiac Death To Cardiac (months) Death
Slide 21: Natural History of the Chronic Heart Failure Patient
Natural History of the Chronic Heart Failure Patient Heart Viability Normal Heart k————> Chronic Heart Failure ———+» Death myocardial injury \ / Hospital —— Admissions for ees Decompensated Heart Failure Time
Slide 22: Event Free Rate
Event Free Rate Kaplan-Meier Plot of Time to First Event (Cardiac Death, HF Hosp, Resuscitated VFib) 1.00; 275) 2.60) 225 i —— T 200 400 600 800 1000 Days to Onset STRATA: — mdgpt=Actve OCensored mdgpt=Actve mdgrp "Placebo Censored mdgrpt =Piacebo
Slide 23: Time to First Event By Treatment Group
Time to First Event By Treatment Group Event Free Rate (Cardiac Death, HF Hosp, Resuscitated VFib) —rT HO 68 0 | High Dose | —T ! Hl —) | | I } Low Dose + pee oom | | H o—26-2 2— | aed Placebo Mid Dose | | | | | \ | \ | | | | \ | | | | | | I 1 1 1 t 200 400 600 800 1000 Days to Onset STRATA ——RNOGRP
Slide 24: Conclusions
Conclusions For personal use only 1. Transendocardial injection of MPCs in patients with chronic heart failure was safe and feasible. 2. Treatment of patients in this study with allogeneic MPCs was not associated with a clinically significant immune response. 3. There was a significant early improve
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