Slide 1: Global Leader in Allogeneic Cellular Medicines for Inflammatory Diseases
mesoblast For personal use only Global Leader in Allogeneic Cellular Medicines for Inflammatory Diseases Corporate Presentation BIOTECH SHOWCASE 2022 JANUARY 2022 ASX: MSB; Nasdaq: MESO
Slide 2: Cautionary Note Regarding Forward-Looking Statements
For personal use only 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, le
Slide 3: Our Mission
For personal use only Our Mission Mesoblast is committed to bringing to market innovative cellular medicines to treat serious and life-threatening illnesses |3
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 For personal use only surface receptors, resulting in orchestration of an anti-inflammatory cascade IL-10 Breg TH1 Proliferation Mesenchymal Cytok
Slide 5: Late-Stage Clinical Pipeline
Late-Stage Clinical Pipeline For personal use only THERAPEUTIC AREA MID-STAGE LATE STAGE COMMERCIAL Phase 2 Phase 3 Acute Graft Versus Host Disease (aGVHD)1 steroid-refractory Acute Respiratory Distress Syndrome (ARDS) initially targeting COVID-19 Chronic Low Back Pain (CLBP)2 due to inflammatory de
Slide 6: Remestemcel-L: Acute Graft versus Host Disease
For personal use only Remestemcel-L Acute Graft versus Host Disease
Slide 7: Acute Graft Versus Host Disease (aGVHD)
Acute Graft versus Host Disease (aGVHD) Serious and Fatal Complication of Allogeneic Bone Marrow Transplantation (BMT) For personal use only PHASE 1 PHASE 2 PHASE 3 Host Tissue Damage Immune Cell Activation Inflammation and End Organ by BMT Conditioning & Cytokine Storm Damage Conditioning Activatio
Slide 8: Children with Steroid-Refractory Acute GVHD at High Risk of Treatment Failure and Death
Children with Steroid-Refractory Acute GVHD at High Risk of Treatment Failure and Death For personal use only 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 corticosteroi
Slide 9: 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 For personal use only • Remestemcel-L was used as first-line therapy in a randomized controlled Phase 3 trial of 260 patients, with SR-aGVHD, including 2
Slide 10: Remestemcel-L Improved Dismal Survival in Children with SR-aGVHD
Remestemcel-L Improved Dismal Survival in Children with SR-aGVHD For personal use only 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 st
Slide 11: Identifying Acute GVHD Patients at High Risk of Non-Response
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 For personal use only Major-Monfried H, et al. MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD. Bloo
Slide 12: 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 For personal use only Response by baseline MAP Survival by Baseline MAP 0.8 MAP > 0.29 0.8 MAP > 0.29 67% vs 10%, p = 0.01 64% vs 10%, p = 0.01
Slide 13: Remestemcel-L: Regulatory & Commercial Update for SR-aGVHD
Remestemcel-L: Regulatory & Commercial Update for SR-aGVHD • Met with the FDA’s OTAT November 2021 For personal use only • 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 mea
Slide 14: Continued Growth in Revenues from Sales of TEMCELL in Japan
Continued Growth in Revenues from Sales of TEMCELL in Japan for SR-aGVHD For personal use only ANNUAL REVENUE FROM TEMCELL ROYALTIES IN JAPAN US$m 8.0 • JCR Pharmaceuticals has exclusive rights to 7.0 Mesoblast’s MSC technology for acute GVHD in 7.2 Japan 6.0 6.6 • FY2021 revenue from TEMCELL® HS In
Slide 15: Remestemcel-L: ARDS due to COVID-19
For personal use only Remestemcel-L Acute Respiratory Distress Syndrome (ARDS) due to COVID-19
Slide 16: Greatest Mortality Reduction Seen in Treated Patients < 65 years
Greatest Mortality Reduction Improved ARDS Severity* Seen in Remestemcel-L Treated Patients < 65 years For personal use only Modified Intent to Treat (mITT) Patients < 65 years old (n=123) Treated Patients (mITT) < 65 years old (n=123) Remestemcel-L vs Control Remestemcel-L vs Control * Measured as
Slide 17: 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 For personal use only Treated Patients (mITT) < 65 years old on Treated Patients (mITT) < 65 years old on Dexamethasone (n=73) through 90-Days Dexamethasone
Slide 18: Regulatory Pathway to Potential EUA for COVID-19 ARDS
Remestemcel-L: Regulatory Pathway to Potential EUA for COVID-19 ARDS For personal use only • 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 mi
Slide 19: Rexlemestrocel-L: Chronic Low Back Pain due to DDD
For personal use only Rexlemestrocel-L Chronic Low Back Pain (CLBP) due to Degenerative Disc Disease (DDD)
Slide 20: A New Paradigm for Treatment of Chronic Low Back Pain due to DDD
Rexlemestrocel-L A New Paradigm for Treatment of Chronic Low Back Pain due to Degenerative Disc Disease For personal use only Burden Minimal Market of Illness Treatment Options Opportunity Healthy Back pain causes more disability Minimal treatment options for Over 7m patients are estimated to
Slide 21: Current Patient Treatment Journey for Discogenic CLBP
Current Patient Treatment Journey (US/EU) for Discogenic CLBP Rexlemestrocel-L (MPC-06-ID) Potential for First-Line DCLBP Refractory to Conservative Treatment For personal use only Rexlemestrocel-L (MPC-06-ID) targeting moderate-to-severe DCLBP Conservative treatments Opioid analgesics Interventiona
Slide 22: Inflammation is at the Core of Degenerative Disc Disease
Chronic Low Back Pain Inflammation is at the Core of Degenerative Disc Disease For personal use only McCann MR and Seguin CA. Notochord Cells in Intervertebral Disc Development and Degeneration. J. Dev. Biol. 2016, 4(1), 3 | 22
Slide 23: Results of 404-Patient Randomized Controlled Phase 3 Trial in CLBP
Results of 404-Patient Randomized Controlled Phase 3 Trial in CLBP: Single Injection of Rexlemestrocel-L + HA Results in >2 Years of Pain Reduction For personal use only Positive results from a single injection of MPC + Hyaluronic Acid (HA) carrier include: Achievement of significant and durable
Slide 24: LS Mean Change in Low Back Pain from Baseline - Entire Study
LS Mean Change in Low Back Pain from Baseline - Entire Study (n=391) For personal use only * = nominal p value < 0.05 MPC+HA vs. Placebo -10 P = MPC + HA vs. Placebo * * LS Mean of Change from Baseline (95% CI) Absence of Non-fatal Ischemic MACE -15 -20 -25 -30 Month 1 Month 3 Month 6 Month 12 Month
Slide 25: LS Mean VAS Change in Low Back Pain - Duration CLBP < Median
LS Mean VAS Change in Low Back Pain from Baseline - Duration CLBP < 68 Month Median (n=194) For personal use only Nominal p-values * = p < 0.05; ** = p < 0.01; *** = p < 0.001 MPC+HA vs. Placebo * * ** *** *** *** *** -10 Absence of Non-fatal Ischemic MACE LS Mean of Change from Baseline (95% CI) -2
Slide 26: Subjects with Minimal to No Pain (VAS ≤ 20)
Subjects with Minimal to No Pain (VAS ≤ 20) MPC + HA Increased Proportion of Patients with Minimal/No Pain (VAS <20) at 12 and 24 Months For personal use only in those with Pain Duration < Median Phase 3 MSB-DR003: Minimal to No Pain – CLBP Duration < Median * = nominal p-value < 0.05 MPC+HA vs. Pla
Slide 27: LS Mean VAS Change in Low Back Pain - Opioid Users
LS Mean VAS Change in Low Back Pain from Baseline - Opioid Users (n=168) For personal use only * = nominal p-value < 0.05 MPC+HA vs. Placebo * * * * * * * 0 Absence of Non-fatal Ischemic MACE LS Mean of Change from Baseline (95% CI) -10 -20 -30 Month 1 Month 3 Month 6 Month 12 Month 18 Month 24 Mont
Slide 28: Pain Medication in Opioid Users
Pain Medication in Opioid Users MPC + HA Increased the Proportion of Patients with Baseline Opioid Use Who Came Off Opioids For personal use only Through 36 Months * = nominal p-value < 0.05 MPC+HA vs. Placebo * * | 28
Slide 29: Next Steps for Rexlemestrocel-L in Chronic Low Back Pain
Next Steps for Rexlemestrocel-L in Chronic Low Back Pain For personal use only 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 endpoin
Slide 30: Rexlemestrocel-L: Chronic Heart Failure with Reduced Ejection Fraction
For personal use only Rexlemestrocel-L Chronic Heart Failure with Reduced Ejection Fraction (HFrEF)
Slide 31: Proposed Mechanism of Action of Intra-Cardiac MPC Administration
Proposed Mechanism of Action of Intra-Cardiac MPC Administration in Treatment of both Heart Failure & Large Vessel Atherosclerosis For personal use only Mesenchymal precursor cells (MPC) Cardiomyocyte key mechanisms of action thought to Survival beneficially impact the heart and the NFkB systemic va
Slide 32: Rexlemestrocel-L Reduced Incidence of 3-Point Composite MACE
Rexlemestrocel-L Reduced Incidence of 3-Point Composite MACE (CV Death, MI or Stroke) Compared to Controls Across All 537 Treated Patients For personal use only Time-to-First-Event for Cardiovascular Death or Non-fatal MI or Non-fatal Stroke Kaplan-Meier log rank statistics | 32
Slide 33: Composite 3-Point MACE and Inflammation
Composite 3-Point MACE and Inflammation For personal use only 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 Rexlemestrocel-L Myocardial Ischemia &/or Diabetes by 37% Reduced Risk of T
Slide 34: Investigational Agents Evaluated for Cardiovascular Risk Reduction: Comparison
Investigational Agents Evaluated for Cardiovascular Risk Reduction Using 3-Point IMM MACE*: Comparison With Rexlemestrocel-L in Patients With Myocardial Ischemia &/or Diabetes For personal use only * TTFE Composite for Cardiovascular Death or Non-fatal MI or Non-fatal Stroke Wang CCL et al. Circulat
Slide 35: Rexlemestrocel-L: Conclusion & Key Next Steps for HFrEF
Rexlemestrocel-L: Conclusion & Key Next Steps for HFrEF For personal use only 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
Slide 36: Thank You
For personal use only Thank You mesoblast