Slide 1: Global Leader in Allogeneic Cellular Medicines for Inflammatory Diseases
mesoblast Global Leader in Allogeneic Cellular Medicines for Inflammatory Diseases Operational Highlights & Financial Results for the Period Ended December 31, 2021 February 2022 ASX: MSB; Nasdaq: MESO
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: Our Mission
Our Mission Mesoblast is committed to bringing to market innovative cellular medicines to treat serious and life-threatening illnesses
Slide 4: Platform Technology – Mechanism of Action
Platform Technology – Mechanism of Action Our mesenchymal precursor/stromal cells respond to and are activated by multiple inflammatory cytokines through surface receptors, resulting in orchestration of an anti-inflammatory cascade IL-10 Breg TH1 Proliferation Proliferation Mesenchymal Precursor / C
Slide 5: Late-Stage Clinical Pipeline
Late-Stage Clinical Pipeline MID-STAGE LATE STAGE THERAPEUTIC AREA Phase 2 Phase 3 COMMERCIAL Acute Graft Versus Host Disease (aGVHD)1 steroid-refractory Acute Respiratory Distress Syndrome (ARDS) initially targeting COVID-19 Inflammatory Bowel Disease (IBD) biologic refractory Crohn’s & ulcerative
Slide 6: Financial Results
Rexlemestrocel-L Financial Results Chronic Low Back Pain (CLBP) due to Degenerative Disc Disease (DDD) Commercialization – Market Overview Manufacturing Remestemcel-L 6 mesoblast © Lonza, reproduced with permission
Slide 7: Financial Highlights
Financial Highlights ❑ Revenues in the quarter were US$2.4 million, primarily from TEMCELL® HS Inj.1 royalties on sales for SR-aGvHD in Japan, which increased 7% on the comparative quarter last year ❑ Cash on hand at the end of the quarter was US$94.8 million, with up to an additional US$40 million
Slide 8: Reduction in R&D Spend; Steady Investment in Manufacturing
Reduction in R&D Spend; Steady Investment in Manufacturing Dec 31, Dec 31, P&L for the 3 months ended 2021 2020 (US$m) (2nd Qtr (2nd Qtr FY2022) FY2021) Commercialization revenue 2.4 2.2 ❑ Decreased R&D Spend: Total Revenue 28% reduction ($4.0m) predominantly due to reduced spend on 2.4 2.2 clinical
Slide 9: Remestemcel-L: Acute Graft Versus Host Disease (aGVHD)
Remestemcel-L Acute Graft Versus Host Disease (aGVHD) Rexlemestrocel-L Chronic Low Back Pain (CLBP) due to Degenerative Disc Disease (DDD) Commercialization – Market Overview 9 mesoblast
Slide 10: Acute Graft Versus Host Disease (aGVHD)
Acute Graft Versus Host Disease (aGVHD) Serious and Fatal Complication of Allogeneic Bone Marrow Transplantation (BMT) PHASE 1 PHASE 2 PHASE 3 Host Tissue Damage Immune Cell Activation Inflammation and End Organ by BMT Conditioning & Cytokine Storm Damage Conditioning regimen, Activation of CD4 & CD
Slide 11: Acute Graft Versus Host Disease (aGVHD)
Acute Graft Versus Host Disease (aGVHD) Serious and Fatal Complication of Allogeneic Bone Marrow Transplantation (BMT) Extremely high unmet medical need ❑ More than 2,000 allogeneic BMTs in children and adolescents in US1 ❑ Despite prophylaxis, ~50% will develop aGVHD2 ❑ First-line treatment is cort
Slide 12: Remestemcel-L: Prior Clinical Data in Children with SR-aGVHD
Remestemcel-L: Prior Clinical Data in Children with SR-aGVHD Consistent Efficacy and Safety Outcomes in a Total of 309 Children from Three Studies Remestemcel-L was used as first-line therapy in a randomized controlled Phase 3 trial of 260 patients, with SR-aGVHD, including 27 children Remestemcel-L
Slide 13: Remestemcel-L Improved Dismal Survival in Children with SR-aGVHD
Remestemcel-L Improved Dismal Survival in Children with SR-aGVHD 2 Steroid Refractory – Remestemcel-L Steroid Refractory – Best Available Therapies 1. Adapted and redrawn from Figure 2 of MacMillan, M.L. et al. Pediatric acute GVHD: clinical phenotype and response to upfront steroids. Bone Marrow Tr
Slide 14: Identifying Acute GVHD Patients at High Risk of Non-Response and Death
Identifying Acute GVHD Patients at High Risk of Non-Response to Treatment and Death MAGIC Algorithm Probability Biomarker Score (MBS, MAP) > 0.29 is a Validated Threshold MAGIC MAGIC MAGIC Test Cohort Validation Cohort 1 Validation Cohort 2 14 Major-Monfried H, et al. MAGIC biomarkers predict long-t
Slide 15: Remestemcel-L Treatment Outcomes
Remestemcel-L Treatment Outcomes Significantly Greater Day 28 Overall Responses and Day 180 Survival in Steroid-Refractory Patients with Baseline MAP ≥ 0.29 Response by Baseline MAP Survival by Baseline MAP Response by baseline MAP Survival by Baseline MAP 0.8 0.8 MAP > 0.29 0.8 0.8 MAP > 0.29 Remes
Slide 16: Remestemcel-L: Regulatory & Commercial Update for SR-aGVHD
Remestemcel-L: Regulatory & Commercial Update for SR-aGVHD Met with the FDA’s OTAT November 2021 OTAT indicated that Mesoblast’s approach to address the outstanding CMC items is reasonable OTAT indicated that the in vitro immunomodulatory activity Mesoblast intends to measure for potency is a reason
Slide 17: Remestemcel-L: ARDS due to COVID-19
Remestemcel-L Acute Respiratory Distress Syndrome (ARDS) Rexlemestrocel-L due to COVID-19 Chronic Low Back Pain (CLBP) due to Degenerative Disc Disease (DDD) Commercialization – Market Overview 17 mesoblast
Slide 18: Remestemcel-L: ARDS due to COVID-19
Remestemcel-L: Acute Respiratory Distress Syndrome (ARDS) due to COVID-19 Clinical Need for Therapeutic Remains High ❑ COVID-19 is a respiratory virus with a high mortality due to a severe inflammatory condition of the lungs called acute respiratory disease syndrome (ARDS) ❑ ARDS is caused by cytoki
Slide 19: Greatest Mortality Reduction & Improved ARDS Severity in Patients < 65
Greatest Mortality Reduction & Improved ARDS Severity* seen in Remestemcel-L Treated Patients < 65 years Modified Intent to Treat (mITT) Patients < 65 years Treated Patients (mITT) < 65 years old (n=123) old (n=123) Remestemcel-L vs Control Remestemcel-L vs Control * Measured as resolution and/or im
Slide 20: Remestemcel-L Plus Dexamethasone Shows Synergy in Mortality Reduction
Remestemcel-L Plus Dexamethasone Shows Synergy in Mortality Reduction and Improvement in ARDS Severity* in Exploratory Population < 65 years old Treated Patients (mITT) < 65 years old on Treated Patients (mITT) < 65 years old on Dexamethasone (n=73) through 90-Days Dexamethasone (n=73) * Measured as
Slide 21: Remestemcel-L: Regulatory Pathway to Potential EUA for COVID-19 ARDS
Remestemcel-L: Regulatory Pathway to Potential EUA for COVID-19 ARDS The FDA has advised Mesoblast that an additional clinical study in COVID ARDS, if statistically positive, could provide a dataset in conjunction with the recently completed 222 patient clinical study that might be sufficient to sup
Slide 22: Remestemcel-L: Inflammatory Bowel Disease
Remestemcel-L Inflammatory Bowel Disease Ulcerative Colitis & Crohn’s Disease mesoblast
Slide 23: Remestemcel-L: Inflammatory Bowel Disease
Remestemcel-L: Inflammatory Bowel Disease Potential Localized Treatment for Ulcerative Colitis & Crohn’s Colitis Refractory to Biologics - High Unmet Need Treatment Options Burden of Illness Market Opportunity Despite recent advances, Up to 80% of patients with More than three million approximately
Slide 24: Remestemcel-L: Ulcerative Colitis & Crohn's Colitis
Remestemcel-L: Ulcerative Colitis & Crohn’s Colitis Results of First Patient Cohort from Randomized Controlled Study Presented at Congress of European Crohn’s and Colitis Organisation (ECCO) ❑ The immunomodulatory effects of remestemcel-L on GI inflammation is being further evaluated in a randomized
Slide 25: Remestemcel-L: Ulcerative Colitis & Crohn's Colitis
Remestemcel-L: Ulcerative Colitis & Crohn’s Colitis Results of First Patient Cohort from Randomized Controlled Study Presented at Congress of European Crohn’s and Colitis Organisation (ECCO) ❑ Key results of the interim analysis performed in the first 12 enrolled patients were as follows: ➢ All UC p
Slide 26: Rexlemestrocel-L: Chronic Low Back Pain due to DDD
Rexlemestrocel-L Chronic Low Back Pain (CLBP) due to Degenerative Disc Disease (DDD) mesoblast
Slide 27: Rexlemestrocel-L: New Paradigm for Chronic Low Back Pain
Rexlemestrocel-L A New Paradigm for Treatment of Chronic Low Back Pain due to Degenerative Disc Disease Burden of Illness Treatment Options Market Opportunity • Back pain causes more • Minimal treatment options for • Over 7m patients are Healthy disability than any other patients with chronic low ba
Slide 28: The Patient Treatment Journey
The Patient Treatment Journey Rexlemestrocel-L Potential for First-Line CLBP associated with DDD, Refractory to Conservative Treatment Rexlemestrocel-L targeting moderate-to-severe DCLBP Conservative Interventional Opioid Surgery Treatments Therapies Analgesics ❑ NSAIDs ❑ Epidural steroid injections
Slide 29: Chronic Low Back Pain: Inflammation Core of Degenerative Disc Disease
Chronic Low Back Pain Inflammation is at the Core of Degenerative Disc Disease McCann MR and Seguin CA. Notochord Cells in Intervertebral Disc Development and Degeneration. J. Dev. Biol. 2016, 4(1), 3 29 mesoblast
Slide 30: Technology Platform – Mesenchymal Precursor Cells (MPC)
Technology Platform – Mesenchymal Precursor Cells (MPC) Potential Mechanisms of Action in Treating Inflammatory Disc Disease Rexlemestrocel-L M1 M1 M1 Mesenchymal precursor cells (MPC) beneficially act in the inflamed disc: TNFα TNFα IL-1β M1 IL-1𝛃 IL-6 1 Reduce neurite ingrowth Rexlemestrocel-L…
Slide 31: Phase 3 Trial Outcomes – Rexlemestrocel-L for Chronic Low Back Pain
Phase 3 Trial Outcomes – Rexlemestrocel-L for Chronic Low Back Pain Single Injection of Rexlemestrocel-L + HA Results in >Three Years of Pain Reduction Positive results from a single injection of MPC + Hyaluronic Acid (HA) carrier include: No appreciable differences in the safety profile of subjects
Slide 32: Phase 3 Trial: Outcome – Entire Study
Phase 3 Trial: Outcome LS Mean Change in Low Back Pain from Baseline - Entire Study (n=404) * = nominal p-value < 0.05 MPC+HA vs. Placebo P = MPC + HA vs. Placebo CI)CI) -10 -10 * * (95% Baseline (95% Absence of Non-fatal Ischemic MACE fromBaseline -15 -15 All Subjects Rexlemestrocel-L+HA -20 -20 fr
Slide 33: Phase 3 Trial: Outcome – Duration Below Median
Phase 3 Trial: Outcome LS Mean VAS Change in Low Back Pain from Baseline - Duration CLBP < 68 Month Median Baseline Duration (n=202) Nominal p-values * = p < 0.05; ** = p < 0.01; *** = p < 0.001 MPC+HA vs. Placebo CI) (95%CI) * * ** *** *** *** *** -10 -10 (95% Baseline Baseline -20 -20 from from Du
Slide 34: Phase 3 Trial: Outcome – Opioid Use
Phase 3 Trial: Outcome Rexlemestrocel-L + HA Increased the Proportion of Patients with Baseline Opioid Use Who Were Not Taking an Opioid at 36 Months Baseline Opioid Users Achieving No Opioid Use * = p < 0.05 MPC+HA vs. Placebo 30.0% * * 25.0% 20.0% Opioid Users 15.0% Rexlemestrocel-L+HA Significant
Slide 35: Next Steps for Rexlemestrocel-L in Chronic Low Back Pain
Next Steps for Rexlemestrocel-L in Chronic Low Back Pain Recently received feedback from the FDA Office of Tissues and Advanced Therapies (OTAT) on the Phase 3 program OTAT agreed with Mesoblast’s proposal for mean pain reduction at 12 months to serve as the primary endpoint of the next trial, with
Slide 36: Rexlemestrocel-L: Chronic Heart Failure with Reduced Ejection Fraction
Rexlemestrocel-L Chronic Heart Failure with Reduced Ejection Fraction (HFrEF) Rexlemestrocel-L Chronic Low Back Pain (CLBP) due to Degenerative Disc Disease (DDD) Commercialization – Market Overview 36 mesoblast
Slide 37: Rexlemestrocel-L: Proposed Mechanism of Action
Rexlemestrocel-L: Proposed Mechanism of Action Intra-Cardiac Administration in Treatment of both Heart Failure & Large Vessel Atherosclerosis NFkB Mesenchymal precursor cells (MPC) beneficially act the heart and the Cardiomyocyte Survival systemic vasculature: M1 M2 M2M2 M1 PDGF M1 IL-6 IL-1β TNFα S
Slide 38: DREAM-HF Phase 3 Trial in HFrEF
DREAM-HF Phase 3 Trial in HFrEF Rexlemestrocel-L Reduced Incidence of 3-Point Composite MACE - CV Death, MI or Stroke - Compared to Controls Across All 537 Treated Patients Time-to-First-Event (TTFE) for Cardiovascular Death or Non-fatal MI or Non-fatal Stroke MACE=Major Adverse Cardiovascular Event
Slide 39: DREAM-HF: 3-Point Composite MACE, High-Risk Patients, Inflammation
DREAM-HF Phase 3 Trial in HFrEF 3-Point Composite MACE, High-Risk Patients (Myocardial Ischemia &/or Diabetes), and Inflammation Rexlemestrocel-L Reduced Risk of 3-Point TTFE In Patients with Myocardial Ischemia and/or Composite IMM MACE in High-Risk Patients with Diabetes with hsCRP≥2 mg/L Rexlemes
Slide 40: Investigational Agents Evaluated for Cardiovascular Risk Reduction
Investigational Agents Evaluated for Cardiovascular Risk Reduction Using 3-Point IMM MACE* Comparison With Rexlemestrocel-L in Patients With Myocardial Ischemia &/or Diabetes * TTFE Composite for non-fatal MI, or non-fatal stroke, or cardiovascular death Wang CCL, et al. Circulation; 2019; 139: 1741
Slide 41: Rexlemestrocel-L: Conclusions & Key Next Steps in HFrEF
Rexlemestrocel-L: Conclusions & Key Next Steps in HFrEF 1 Transendocardial delivery of 150 million allogeneic MPCs (rexlemestrocel-L) was safe and did not elicit any clinically meaningful immune-related responses 2 Over a mean follow-up of 30 months, a single rexlemestrocel-L dose on top of maximal
Slide 42: Thank You
mesoblast Thank You