Slide 1: Clinically Meaningful Outcome in Phase 2b Trial of MPC-150-IM in LVAD Recipients
Clinically Meaningful Outcome in Phase 2b Trial of MPC-150-IM in LVAD Recipients Provides Pathway for Regulatory Approval 12 November 2018 Nasdaq: MESO ASX: MSB
Slide 2: Cautionary Note Regarding Forward-Looking Statements
CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS This presentation includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, perf
Slide 3: MPC-150-IM for End-Stage Heart Failure for Patients Implanted with LVADs
MPC-150-IM for End-Stage Heart Failure for Patients Implanted with LVADs |3 |3
Slide 4: MPC-150-IM: Adjunctive Therapy to Improve Clinical Outcomes in LVAD Patients
MPC-150-IM: Adjunctive Therapy to Improve Clinical Outcomes in LVAD Patients In the USA, there are approximately 250,000–300,000 patients annually who Burden of suffer from advanced systolic heart failure (NYHA Class IIIb–IV). 1 Illness Despite optimal medical therapy (excluding mechanical assis
Slide 5: INTERMACS Adverse Event Rates in LVAD Patients
INTERMACS* Adverse Event Rates in LVAD Patients: Most Common Cause of Non-surgical Hospitalization is Major GI Bleeding1 *Interagency Registry for Mechanically Assisted Circulation (INTERMACS): Events per 100 Patient-Months in the First 12 Months Post-Implant, based on 7,286 patients with CF-LVADs b
Slide 6: Angiopoietin-2 Proposed Pathway of Angiogenesis and GI Bleeding During CF-LVAD
Proposed Pathway of Angiogenesis and Non-surgical GI Bleeding During CF-LVAD Altered Shear Stress vWF Degradation This image cannot currently be displayed. Angiopoietin-2 Factors (HIP) Inducible Hypoxia Hypoxia Angiogenesis Angiodysplasia Splanchnic Inflammation: Hypoperfusion IL-6, IL-1, TNFα An in
Slide 7: MPCs Reduced Major GI Bleeding in Patient Pilot Trial
MPCs Reduced Major GI Bleeding in 30 Patient Pilot Trial1 Cumulative Incidence for Control, 0.4 (95% CI, 0.10, 0.69) Cumulative Incidence for MPC, 0.1 (95% CI, 0.02, 0.28) Gray’s Test for Equality of CIF, P = 0.041 Readmitted Population Days to First Non-Surgical Major Bleeding Requiring Re-admissio
Slide 8: The 21st Century Cures Act (Cures Act)
The 21st Century Cures Act (Cures Act) Legislation for An Expedited Approval Path for Cellular Medicines Designated as Regenerative Medicine Advanced Therapies (RMAT) Cellular medicines may be designated as regenerative advanced therapies, if they are intended to treat, modify, reverse, or cure a
Slide 9: FDA Regulatory Interaction for MPC-150-IM using LVADs
FDA Regulatory Interaction for MPC-150-IM using LVADs December 2017 FDA grants RMAT designation for Mesoblast’s novel MPC therapy for the treatment of heart failure due left ventricular systolic dysfunction of either ischemic or non-ischemic etiology in patients with LVADs. Based on pilot trial data
Slide 10: Can MPCs Reduce GI Bleeding Complications in End-Stage Heart Failure Patients with LVADs?
Can MPCs Reduce GI Bleeding Complications in End-Stage Heart Failure Patients with LVADs? Rationale Intra-myocardial injections of allogeneic MPCs may reduce myocardial and systemic inflammation MPCs improve coronary and systemic artery endothelial dysfunction in ovine systemic inflammation MP
Slide 11: 2018 American Heart Association Scientific Sessions - Late Breaking
2018 American Heart Association Scientific Sessions - Late Breaking | 11 | 11
Slide 12: Objective and Target Population
Objective and Target Population Objective : To assess whether one-time injections of high dose MPCs into the native myocardium of LVAD recipients is safe and improves cardiac recovery Inclusion Criteria Exclusion Criteria Adults with advanced HF Percutaneous LVAD or BV support − Ischemic Plann
Slide 13: Trial Design
Trial Design Assessed for eligibility (n=637) Excluded (N=478) • Did not meet inclusion criteria (N=276) • Refused to participate (N=150) • Other (N=52) Randomized (N=159) Allocation MPC (150M) Sham Control (N=106) 2:1 (N=53) Follow-up at 6 Months • Withdrew (N=0) • Withdrew (N=2) • Death (N=10) • D
Slide 14: Mucosal Bleeding at 6 Months
Mucosal Bleeding at 6 Months Rate of GI/Epistaxis Bleeding MPC (n = 106) Control (n = 53) P-value Event Rate Event Rate (100-Pt-Months) (100-Pt-Months) 3.8 15.9 <0.001 | 14
Slide 15: Serious AEs & Hospitalizations at 6 Months
Serious AEs & Hospitalizations at 6 Months MPC Control Neurological dysfunction 4.4 3.3 Rate per 100 pt-months Hospitalizations Right heart failure 3.6 100 pt-months 5.3 (p=0.03) 0.07 Rate per Major infections 9.1 GI Bleeding 10.2 0.21 Major device malfunction 3.5 3 7.7 0.68 All arrhythmias 6.6 All
Slide 16: Successful Temporary Weans from LVAD Support
Successful Temporary Weans from LVAD Support Average proportion of successful 70 66% 62%62% temporary weans: 59%58% − 61% in MPC vs. 58% in control 60 53% Proportion of Successful − RR=1.08 (95% CI 0.83-1.41; p=0.55) 50 Posterior probability that MPC 40 Weans increased likelihood of successful 3
Slide 17: Limitations
Limitations High rate of pump thrombosis reduced number of evaluable wean attempts Enrolled heterogeneous study population − Ischemic/non-ischemic HF, BTT/DT, 2 types of devices − Increased variability may have reduced likelihood of detecting Rx effect Although all bleeding events & transfusio
Slide 18: Exploratory Subgroup Analyses
Exploratory Subgroup Analyses Interaction of Rx and Pre-determined Subgroups on Wean Success Rate over 6 Months | 18
Slide 19: Primary Safety Endpoint & Sensitization
Primary Safety Endpoint & Sensitization No patients developed a primary safety stopping event Allosensitization to Class I HLA antigens − 26% MPC vs 9.4% Control − Between-group difference: 16.5% (95% CI: 5 to 28%) Allosensitization to Class II HLA antigens − Similar in control and MPC patient
Slide 20: Conclusions
Conclusions Succeeded in achieving the FDA identified clinically meaningful outcome of reduction in GI bleeding and related hospitalization Results confirm the previous pilot trial, which also demonstrated significant reduction in GI bleeding and related hospitalization in MPC treated LVAD patie
Slide 21: Acknowledgements
Acknowledgements This trial was supported by a cooperative agreement (U01-HL088942) funded by NHLBI and NINDS, of the National Institutes of Health (NIH), and the Canadian Institutes for Health Research (CIHR) Mesoblast provided MPCs and cryoprotective medium We would like to thank the patient
Slide 22: Questions & Answers
Questions & Answers | 22 | 22
Slide 23: Appendix
Appendix | 23 | 23
Slide 24: Roles of Angiopoietin-2 in Exacerbating Cardiac Hypoxia and Inflammation
Roles of Angiopoietin-2 in Exacerbating Cardiac Hypoxia and Inflammation in Association with Myocardial Ischemia • Disintegration of endothelial Myocardial tissue cell (EC) barrier ischemia and hypoxia • Abnormal vascular remodeling • Robust inflammatory response • Extracellular matrix disorganizati
Slide 25: Effects of CF-LVAD on TNF-α, ANG-2 and ANG-1 on GI Bleeding
Effects of CF-LVAD on TNF-α, ANG-2 and ANG-1 on GI Bleeding TNF-α in CF-LVAD Patients1 Low TNF-α Non-surgical Bleeding Elevated TNF-α level is a key regulator of Freedom from altered angiogenesis, pericyte apoptosis and expression of tissue factor High TNF-α High TNF-α levels are associated with
Slide 26: MPCs Improve Coronary Artery Endothelial Dysfunction In A Sheep Model
MPCs Improve Coronary Artery Endothelial Dysfunction In A Sheep Model of Systemic Inflammation Source: Dooley et al. Effect of MPCs on the systemic inflammatory response and endothelial dysfunction in an ovine model of collagen-induced arthritis. PLOS One, May 7, 2015. | 26
Slide 27: MPCs Improve Digital Artery Endothelial Dysfunction In A Sheep Model
MPCs Improve Digital Artery Endothelial Dysfunction In A Sheep Model of Systemic Inflammation Source: Dooley et al. Effect of MPCs on the systemic inflammatory response and endothelial dysfunction in an ovine model of collagen-induced arthritis. PLOS One, May 7, 2015. | 27