MESOBLAST LTD — Investor Presentation 2021

Dec 5, 2021

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meso blast

DREAM HF Trial: Rexlemestrocel-L (MPCs) in the Treatment of Heart Failure with Reduced Ejection Fraction (HFrEF) Presentation at the 18th Global CardioVascular Clinical Trialists Forum (CVCT), Washington DC

DECEMBER 2021

ASX: MSB; Nasdaq: MESO

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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, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forwardlooking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. All statements other than statements of historical facts contained in this presentation are forward-looking statements. Words such as, but not limited to, “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “targets,” “likely,” “will,” “would,” “could,” and similar expressions or phrases identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and future events , recent changes in regulatory laws, and financial trends that we believe may affect our financial condition, results of operation, business strategy and financial needs. These statements may relate to, but are not limited to: expectations regarding the safety or efficacy of, or potential applications for, Mesoblast's adult stem cell technologies; expectations regarding the strength of Mesoblast's intellectual property, the timeline for Mesoblast's regulatory approval process, and the scalability and efficiency of manufacturing processes; expectations about Mesoblast's ability to grow its business and statements regarding its relationships with current and potential future business partners and future benefits of those relationships; statements concerning Mesoblast's share price or potential market capitalization; and statements concerning Mesoblast's capital requirements and ability to raise future capital, among others. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. You should read this presentation together with our financial statements and the notes related thereto, as well as the risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblast's actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, include, without limitation: risks inherent in the development and commercialization of potential products; uncertainty of clinical trial results or regulatory approvals or clearances; government regulation; the need for future capital; dependence upon collaborators; and protection of our intellectual property rights, among others. Accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise.

Our Mission

Mesoblast is committed to bringing to market innovative cellular medicines to treat serious and life-threatening illnesses

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Chronic Heart Failure: Rising Incidence & High Mortality

• Cardiovascular disease (CVD) remains the leading cause of death in the United States[1]

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• Heart failure affects 6.5 million patients in the US and 26 million patients globally. As populations age, the prevalence is increasing[2]

• Chronic heart failure is a progressive disease with a high mortality that approaches 50% at 5 years[2,3] , and at least 75% after an initial hospitalization[4]

• Patients with heart failure are also at high risk of recurrent major adverse cardiac events involving large vessels (heart attacks / strokes)

New therapies for chronic heart failure reduce recurrent hospitalizations due to cardiac decompensation, however they do not materially improve cardiac mortality or major ischemic events (heart attacks/strokes)

1. Muntner BEJ, et al. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. Feb 19, 2019. 2. United States Food & Drug Administration. Treatment for Heart Failure: Endpoints for Drug Development. Draft Guidance. June 2019. 3. Taylor CJ, et al. Trends in survival after a diagnosis of heart failure in the United Kingdom 2000-2017: population-based cohort study. BMJ. 2019;364:I223. 4. Shah KS, et al. Heart Failure with Preserve, Borderline, and Reduced Ejection Fraction; 5-Year Outcomes. JACC . 2017;Nov12.

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Proposed Mechanism of Action of Intra-Cardiac MPC Administration in Treatment of both Heart Failure & Large Vessel Atherosclerosis

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Mesenchymal precursor cells (MPC) key mechanisms of action thought to beneficially impact the heart and the systemic vasculature:

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• Reduction in cardiac and systemic inflammation

• Reversal of endothelial dysfunction

• Induction of microvascular network within viable heart muscle

• Reduction in heart muscle death

hs-CRP synthesized in the liver is the systemic consequence of intracardiac IL-6 production

Modified from Borow KM, Yaroshinsky A, Greenberg B, Perin E. Phase 3 DREAM-HF Trial of Mesenchymal Precursor Cells in Chronic Heart Failure: A Review of Biological Plausibility and Implementation of Flexible Clinical Trial Design. Circ Res. 2019;125:265-281

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DREAM-HF Trial: Overview

• 18 to ≤80 years of age

• NYHA class II / III, LVEF ≤ 40%

• Receiving optimal medical therapies for heart failure at stable and tolerated doses for at least 1 month before study intervention

• No option for percutaneous coronary intervention or coronary artery bypass graft surgery

• Enrichment criteria:

• At least 1 heart failure hospitalization or outpatient visit requiring intravenous diuretic, vasodilator, and/or positive inotropic therapy >1 month but ≤9 months before initiation of screening procedures and/or

• Plasma levels of NT-pro-BNP >1000 pg/mL (>1200 pg/mL for patients with atrial fibrillation)

• Prospective, randomized, double-blind, sham controlled

• 1:1 randomization: Single administration procedure of 150 million allogeneic MPC delivered by transendocardial image-guided injection vs sham-control procedure

• All medical therapies for heart failure continued for all patients

• 565 randomized patients; 537 received treatment

• Mean patient follow-up 30 months

• Prospective adjudication by treatment-blinded independent Clinical Endpoints Committee (CEC) of all Major Adverse Cardiovascular Events (MACE) including potential Cardiovascular death, cardiac deaths or non-cardiac vascular deaths

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Clinically Significant Endpoints in Persistent HFrEF

Pre-Specified Endpoints

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• 3-Point Composite MACE Endpoint

1. Mortality (cardiovascular death, all-cause cardiac death, cardiac death from pump failure)

2. Irreversible Morbidity (non-fatal myocardial infarction, non-fatal cerebrovascular accident)

4. Irreversible Morbidity or Mortality: IMM (cardiovascular/cardiac death, or non-fatal MI, or non-fatal stroke)

3. Non-fatal Decompensated HFrEF Morbidity Events (non-fatal hospitalization or urgent care treatment for decompensated HFrEF &/or successfully resuscitated cardiac death associated with high-grade ventricular arrythmias)

NOTE: Adjudication of all deaths in DREAM-HF trial (including CV, all-cause cardiac, or non-cardiac) was prospectively performed by the treatment-blinded independent Clinical Endpoints Committee (CEC) at the Brigham & Women’s Hospital using pre-specified causal categories, defined in the study’s Adjudication Operations Manual.

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Rexlemestrocel-L Did Not Further Reduce Frequency of Hospitalization for Worsening HF Symptoms Over Maximal Standard of Care

All Patients (n=537) HR: 1.2 p=0.4

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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 for Cardiovascular Death or Non-fatal MI or Non-fatal Stroke

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Evaluation of Rexlemestrocel-L on 3-Point IMM MACE in Pre-Specified Patient Populations With Reproducibly High-Risk for Poor Outcomes:

Greatest Treatment Effect in Patients with Micro- or Macro- Vascular Disease (Myocardial Ischemia and/or Diabetes)

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1 Chronic HF of ischemic etiology includes epicardial CAD, defined as documented stenosis of at least 50% in one or more major epicardial coronary arteries, documented prior coronary artery revascularization, and/or documented prior MI 2 Diabetes includes patients with end-organ involvement due to microvascular disease

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Myocardial Ischemia &/or Diabetes in Control Patients in DREAM-HF Trial Identifies Subgroup with Worse Outcomes, as Measured by 3-Point IMM MACE, than other HFrEF Controls

3-Point TTFE Composite IMM MACE (n=276 Control Patients) Myocardial Ischemia &/or Diabetes (n=192) vs. Non-Ischemia/Non-Diabetes (n=84)

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Kaplan-Meier log rank statistics

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Rexlemestrocel-L Reduced Risk of 3-Point TTFE Composite IMM MACE in High-Risk Patients with Myocardial Ischemia &/or Diabetes by 36%

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Ischemic &/or Diabetic Patients Non-Ischemic/Non-Diabetic Patients
= =
(n 385) (n 152)
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Kaplan-Meier log rank statistics

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Pre-Specified Hypotheses

• hs-CRP is a validated biomarker for risk of vascular disease, accelerated atherosclerosis, myocardial infarction, and heart failure severity

• Cut-points of <2mg/L, ≥ 2 mg/L, ≥ 3mg/l, and ≥ 4mg/L were pre-specified for sensitivity analyses in the DREAM-HF SAP

• Values for hsCRP ≥2 mg/L have previously been used as a threshold for systemic inflammation in cardiovascular disease patient populations, including heart failure[1]

• High levels of hs-CRP may:

• Be circulating biomarkers to identify those patients with evidence of inflammatory etiology to their HFrEF

• Identify those HFrEF patients most likely to respond to the anti-inflammatory effects of rexlemestrocel-L treatment

• Identify those HFrEF patients with micro- or macro-vascular disease who may be most likely to benefit from rexlemestrocel-L therapy

1Pellicori P, Zhang J, Cuthert J, et.al. High sensitivity C-reactive protein in chronic heart failure: patient characteristics, phenotypes, and mode of death. Cardiovasc Res 2020;116:91-100

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Composite 3-Point MACE and Inflammation

In Patients with Myocardial Ischemia and/or Diabetes with hsCRP≥2 mg/L Rexlemestrocel-L Reduced Risk of TTFE for 3-Point MACE by 54%

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Kaplan-Meier log rank statistics

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Investigational Agents Evaluated for Cardiovascular Risk Reduction Using 3-Point IMM MACE*: Comparison With Rexlemestrocel-L in Patients With Myocardial Ischemia &/or Diabetes

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• TTFE Composite for Cardiovascular Death or Non-fatal MI or Non-fatal Stroke

Wang CCL et al. Circulation 2019; 139: 1741-1743. McGuire DK et al. JAMA Cardiol. 2021; 6:148-158.

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Conclusion & Key Next Steps

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 standard of care significantly reduced:

3. Composite of cardiovascular death or non-fatal MI or non-fatal stroke in all 537 patients

4. Composite of cardiovascular death or non-fatal MI or non-fatal stroke in all 537 patients

5. A hierarchical analysis of pre-specified risk stratification showed greatest benefit in patients with myocardial ischemia and/or diabetes (72% of total treated population)

6. In controls (treated with maximal current therapies for heart failure), the presence of myocardial ischemia and/or diabetes resulted in 1.9-fold greater risk of 3-Point MACE versus other control patients with heart failure

7. Rexlemestrocel-L reduced 3-Point MACE in myocardial ischemics and/or diabetics by 37%

8. Greatest benefit in patients with elevated CRP at baseline with reduction in 3-Point MACE of 54% (n = 212)

9. Mesoblast to formally submit to FDA its new analyses of outcomes in high-risk HFrEF patients with diabetes and/or myocardial ischemia to agree on a potential pathway to approval

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