MESOBLAST LTD — Investor Presentation 2021

Jan 11, 2021

Rexlemestrocel-L for Cardiovascular Diseases

Heart Failure Phase 3 Trial Top Line Results

ASX: MSB; Nasdaq: MESO January 2021

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

Product Pipeline

PRODUCT CANDIDATE	THERAPEUTIC AREA	PHASE 1/2	PHASE 3	REGISTRATION	MESOBLAST COMMERCIAL RIGHTS	COMMERCIAL PARTNERS
Remestemcel-L (RYONCILTM)		Acute GVHD - Pediatric			Global	*
	Pediatric & adult	Acute GVHD - Adult			ex-Japan
	systemic inflammatory diseases	Acute Respiratory Distress Syndrome COVID-19, Influenza, Other Causes			Global	#
		Refractory Inflammatory Bowel Disease			Collaboration
Rexlemestrocel-L	Localized	Advanced Heart Failure			Global
	inflammatory diseases	End-Stage Ischemic Heart Failure			ex-China
		Chronic Low BackPain			Global ex-EUR, LATAM

This chart is figurative and does not purport to show individual trial progress within a clinical program

⃰ Mesoblast has the right to use data generated by JCR Pharmaceuticals Co Ltd in Japan to support its development and commercialization plans for remestemcel-L in the US and other major healthcare markets, including for GVHD, Hypoxic Ischemic Encephalopathy and Epidermolysis Bullosa

The closing of the license agreement is subject to the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and certain other conditions

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

GlobalIPEstateProvidesSubstantialCompetitiveAdvantage

• Extensive patent portfolio with protection extending through 2040 in all major markets
• Over 1,100 patents and patent applications (82 patent families) across all major jurisdictions
• Covers composition of matter, manufacturing, and therapeutic applications of mesenchymal lineagecells
• Provides strong global protection in areas of our core commercial focus against cell-based competitor products
• When outside our core commercial areas, may consider granting rights to third parties who require access to our patent portfolio to commercialize their products
• Mesoblast receives royalty income from its patent licensee TiGenix, S.A.U., a wholly owned subsidiary of Takeda, on its worldwide sales of its product Alofisel® for the treatment of complex perianal fistulas in adult patients with Crohn's disease, as well as milestone payments

Commercial Scale Manufacturing Capability

• Scalable allogeneic "off-the-shelf" cellular platforms
• Manufacturing meets stringent criteria of international regulatory agencies
• Robust quality assurance processes ensure final product with batch-to-batch consistency and reproducibility
• Projected increase in capacity requirements for maturing pipeline

Manufacturing Remestemcel-L

© Lonza, reproduced with permission

• Proprietary xeno-free technologies will increase yields and output
• Moving to 3D bioreactors will reduce labor and improve manufacturing efficiencies
• These innovations will significantly reduce cost of goods

Overview of Collaboration with Novartis for Remestemcel-L

• Worldwide license and collaboration agreement with Novartis for the development, manufacture and commercialization of remestemcel-L*
• Initial focus is on the treatment of acute respiratory distress syndrome (ARDS) and other respiratory conditions
• Novartis intends to initiate a Phase 3 study in non-COVID-19-related ARDS after the anticipated closing of the license agreement and outcome of the current COVID-19 ARDS study
• Mesoblast will retain full rights and economics for remestemcel-L for graft versus host disease (GVHD), and Novartis has an option to, if exercised, become the commercial distributor outside of Japan
• For most non-respiratory indications, the parties may co-fund development and commercialization on a 50:50 profit-share basis

^* The closing of the license agreement is subject to the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and certain other conditions

SR-aGVHD Regulatory & Commercial Update

• On August 13 2020, results from 309 children with steroid refractory acute graft versus host disease (SR-aGVHD) treated with remestemcel-L were presented to the Oncologic Drugs Advisory Committee (ODAC) of the United States Food and Drug Administration (FDA)
• The ODAC panel voted 9:1 that the available data support the efficacy of remestemcel-L in pediatric patients with SR-aGVHD*
• Despite the overwhelming ODAC vote, on September 30, the FDA provided Mesoblast with a Complete Response Letter
• Mesoblast intends to meet with the FDA during Q1 CY2021 through a well-established process for continuing discussions on the potential for accelerated approval with a post-approval commitment to conduct an additional randomized controlled study

MPC-06-ID for Chronic Low Back Pain

• Phase 3 trial of MPC-06-ID for chronic low back pain in 404 patients:
• − Final study visits for all patients have been completed
• − Ongoing quality review of all data is being completed at the study sites
• − Data readout expected shortly
• Continued operational progress in strategic partnership for chronic lower back pain with Grünenthal in Europe to complete clinical protocol design, obtain regulatory input, and receive clearance from European regulatory authorities to begin European Phase 3 trial
• Results from the Phase 3 trials will be considered pivotal to support regulatory approval in the US, as well as in Europe

DREAM HF

• Phase 3 Trial in Chronic Heart Failure
• Rexlemestrocel-L Mechanism of Action

Chronic Heart Failure: Rising Incidence & High Mortality

• Cardiovascular disease (CVD) remains the leading cause of death in the United States1
• Heart failure affects 6.5 million patients in the US and 26 million patients globally. As populations age, the prevalence is increasing2
• Chronic heart failure is a progressive disease with a high mortality that approaches 50% at 5 years2,3, and at least 75% after an initial hospitalization4
• 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.

Myocardial Infarction & Stroke in Chronic Heart Failure: Current Unmet Needs

• Each year in the United States approx. 805,000 people suffer from a myocardial infarction (heart attack) and approx. 795,000 people experience a new or recurrent stroke1
• A major consequence of a heart attack is chronic heart failure, and patients with chronic heart failure are at higher risk of recurrent heart attacks and strokes2
• Atherosclerosis is a chronic inflammatory condition associated with endothelial dysfunction3
• Cardiovascular complications associated with atherosclerosis in chronic heart failure patients may respond to potent anti-inflammatory therapeutic approaches

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

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

• Reduction in cardiac and systemic inflammation
• Reversal of endothelial dysfunction
• Induction of microvascular network within viable heart muscle
• Reduction in heart muscle death

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

Rexlemestrocel-L for Chronic Heart Failure

Treatment Algorithm in Progressive Heart Failure

Progressive Vascular (Endothelial) Dysfunction and Heart Failure

1. GlobalData-PharmaPoint Heart Failure (2016); McMurray et al., 2012;Yancy et al., 2013, 2016 ACC/AHAHFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure.

DREAM HF

• Phase 3 Trial in Chronic Heart Failure
• Rexlemestrocel-L vs Sham Clinical Outcomes

DREAM HF: Overview of Phase 3 Trial

• Mesoblast's allogeneic cell therapy rexlemestrocel-L has a dual mechanism of action that involves immunomodulation and improvement in blood vessel integrity/function
• DREAM-HF Phase 3 trial was designed to evaluate whether rexlemestrocel-L could improve morbidity and mortality in advanced chronic heart failure patients
• Trial design: 1:1 randomized, controlled, double blinded; conducted over 55 sites across North America using 150 million cell dose vs control in 565 patients
• Primary endpoint: reduction in recurrent heart failure-related hospitalizations
• Additional pre-specified key clinical endpoints:
• Reduction in ischemic cardiovascular events (heart attack / stroke)
• Reduction in recurrent hospitalizations due to ischemic events (heart attack / stroke)
• Reduction in death due to cardiac causes
• Major Adverse Cardiac Events (MACE: heart attack, stroke or cardiac death)

DREAM HF: Patient Flow

DREAM HF: Baseline FAS Summary Data by NYHA CLASS II or III

Parameter	Units		TOTAL $(n=537)$	NYHA II		NYHA III
NYHA Functional Class	Number, %			206	38.4%	331	61.6%	$\blacktriangledown$
Ш	Number, %	206	38.4%
Ш	Number, %	331	61.6%
(537 unique subjects) Age	Yrs (mean)	62.7	64.0	62.2	63.0	63.1	65.0
Sex	(537 unique subjects)*
Males	Number, %	428	79.7%	168	81.6%	260	78.5%
Females	Number, %	109	20.3%	38	18.4%	71	21.5%
Race	(537 unique subjects)
White	Number, %	414	77.1%	166	80.6%	248	74.9%
Black	Number, %	99	18.4%	34	16.5%	65	19.6%
Asian	Number, %	7	1.3%	$\overline{2}$	1.0%	5	1.5%
Other	Number, %	17	3.2%	4	1.9%	13	3.9%
Ethnic Group	(537 unique subjects)
Hispanic	Number, %	34	6.3%	11	5.3%	23	6.9%
Blood pressure
Systolic	mmHg (mean)	117.1	114.0	117.2	116	117	113
Diastolic	mmHg (mean)	70.2	70.0	71.2	71	69.5	68
Heart rate	Beats/min (mean)	72.3	71.0	70.9	70	73.1	71
Body weight	kg (mean, median)	92.8	90.9	91.8	89.2	93.4	92.5

DREAM HF: Baseline FAS Summary Data by NYHA CLASS II or III

TOTAL Units Parameter $(n=537)$			NYHA II		NYHA III
Non-Ischemic vs Ischemic Cardiomyopathy (per baseline CRF)
Ischemic	Number, %	303	56.4%	111	53.9%	192	58.0%
Non-ischemic	Number, %	234	43.6%	95	46.1%	139	42.0%
Past Myocardial infarction	Number, %	280	52.1%	106	51.5%	174	52.6%
Coronary revascularization
Previous PCI and/or CABG (unique subjects) Number, %		307	57.2%	119	57.8%	188	56.8%
Echocardiographic Imaging	(530 unique subjects)
Left ventricular ejection fraction	% (mean, median)	28.6	28.6	28.6	29.0	28.6	28.5
Left ventricular end-systolic volume	mL (mean, median)	149.8	135.9	155.4	137.4	146.2	135.0
$\leq 100$	number, %	101	18.8%	41	19.9%	60	18.1%
>100	number, %	429	79.9%	163	79.1%	266	80.4%
missing	number, %	7	1.3%	$\overline{2}$	1.0%	5	1.5%
Left ventricular end-diastolic volume	mL (mean, median)	206.5	194.0	213.1	193.7	202.3	194.3
6MWT distance (537 unique subjects)	m (mean, median)	331.5	340.5	356.8	367	311.7	329.2
Biomarkers
NT-proBNP	pg/mL (mean, median)	2166	1400	1809	1322	2390	1458
hsCRP	mg/L (mean, median)	5.3	2.5	3.6	$\overline{2}$	6.4	3.3
AICD without CRT	Number, %	245	99 84.0%	81.6%	146	85.5%
CRT-D	Number, %	206		69		137
Laboratory measurements
Sodium	mequiv/L (mean)	139.5	140.0	139.5	140.0	139.6	140.0
Potassium	mequiv/L (mean)	4.5	4.5	4.5	4.5	4.5	4.5
Creatinine	mg/dL (mean)	1.2	1.1	1.1	1.1	1.3	1.2
BUN	mg/dL (mean)	24.2	21.0	22.7	20.5	25.2	22.0
HbA1c	% (mean)	6.4	6.1	6.3	6.0	6.4	6.2
Hemoglobin	g/dL (mean)	13.6	13.7	13.8	13.9	13.5	13.5
Hematocrit	% (mean)	41.8	41.8	42.3	42.4	41.5	41.1

DREAM HF

• Recurrent Decompensated Heart Failure Hospitalization Events
• Non-Fatal Ischemic MACE (Heart attacks or Strokes)

Rexlemestrocel-L Did Not Reduce Non-Fatal Heart Failure MACE (Recurrent Decompensated Heart Failure Events or High-Grade Arrhythmias)

Rexlemestrocel-L Significantly Reduced Incidence of Ischemic MACE (MI, Stroke) by 60% Relative to Controls (n=537 Patients)

Elevated Baseline CRP Levels Predict Rexlemestrocel-L Benefit on Incident Heart Attacks or Strokes … Consistent with Anti-Inflammatory MOA

	ALL
TTFE ANALYSIS
REX Effect Compared with Controls	60%
P-value	0.002
COVARIATES
Ischemic	P = 0.0098
Non-ischemic	P = 0.0995
hsCRP>2	P = 0.0045
hsCRP>3	P = 0.0065
hsCRP>4	P = 0.0430

Myocardial Infarction or Cerebrovascular Accident

Rexlemestrocel-L Significantly Reduced Incidence of Ischemic MACE (MI, Stroke) by 57% & 67% Relative to Controls In NYHA Class II & III, respectively

Rexlemestrocel-L Significantly Reduced Hospitalization Rates from Non-Fatal MI or Stroke in All Patients, with Similar Effect Size in NYHA Class II and Class III Patients

• Death From Cardiac Causes (CV Death)

High Baseline CRP and NT-proBNP are Significant Predictors of Rexlemestrocel-L Treatment Benefit on Cardiac Death

Cardiac Death

	ALL	Class II	Class III
COVARIATES*
NYHA Class II	P = 0.0430
NYHA Class III	P = 0.4630
hsCRP>2	P = 0.1634	P = 0.0062
hsCRP>3		P = 0.0122
hsCRP>4		P = 0.0273
NT-proBNP		P = 0.0139

* Multi-variate regression analysis using COX proportional hazards

Rexlemestrocel-L Reduced Cardiac Death by 60% in NYHA Class II Patients

DREAM HF

• Three-Point MACE (CV Death, MI or Stroke)

Rexlemestrocel-L Significantly Reduced 3-Point Composite MACE (CV Death, MI or Stroke) Compared to Controls Across All 537 Patients

Rexlemestrocel-L Significantly Reduced 3-Point Composite MACE (CV Death, MI or Stroke) in 206 NYHA Class II Patients

Rexlemestrocel-L for Chronic Heart Failure

Treatment Algorithm in Progressive Heart Failure

Progressive Vascular (Endothelial) Dysfunction and Heart Failure

1. GlobalData-PharmaPoint Heart Failure (2016); McMurray et al., 2012;Yancy et al., 2013, 2016 ACC/AHAHFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure.

Rexlemestrocel-L Phase 3 Trial Conclusions

• Rexlemestrocel-L may provide a major breakthrough in reducing heart failure progression and mortality when used early (class II disease), and may provide durable protection from heart attacks or strokes in high-risk patients
• 60% reduction in incidence of ischemic MACE (heart attack or stroke) across entire 537 patient study population, irrespective of NYHA class II or III, ischemic or non-ischemic etiology (p=0.002)
• 30% reduction in incidence of three-point MACE (cardiac death, heart attack or stroke) across entire 537 patient study population (p=0.027)
• 55% reduction in incidence of three-point MACE (cardiac death, heart attack or stroke) in NYHA class II patients (n=206) (p=0.009)
• 60% reduction in cardiac death in NYHA class II patients (p=0.037) and prevention of progression to NYHA class III rate of cardiac death
• Based on observed reduction in mortality and morbidity in this Phase 3 trial, Mesoblast intends to meet with the United States Food and Drug Administration (FDA) to discuss potential approval pathways