MESOBLAST LTD — Interim / Quarterly Report 2023

May 25, 2023

mesoblast

Global Leader in Allogeneic Cellular Medicines for Inflammatory Diseases Operational Highlights and Financial Results for the Quarter Ended March 31, 2023

May 2023 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 forward- looking 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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Investment Highlights

Novel Allogeneic Cell Therapy Platform

Developing off-the-shelf, allogeneic cellular medicines based on proprietary mesenchymal stromal cell (MSC) technology platforms to enable treatment without the need for donor matching or immunosuppression

Remestemcel-L for SR-aGVHD

FDA review of BLA with PDUFA goal date August 2, 2023, for children with steroidrefractory acute graft versus host disease (SR-aGVHD). FDA has now conducted the PreLicense Inspection (PLI) of the manufacturing process for remestemcel-L

Rexlemestrocel-L for CLBP

First Phase 3 completed for discogenic chronic low back pain (CLBP). RMAT granted by FDA. Progressing towards initiation of a second pivotal Phase 3 study mid-CY2023

Rexlemestrocel-L for HFrEF

First Phase 3 completed for heart failure with reduced ejection fraction (HFrEF) Class II/III patients. RMAT granted by FDA for end-stage HFrEF patients with an LVAD

Finances

Last 12 months revenue of US$7.6 million from royalties; Cash-on-hand was US$48.8 million, pro-forma cash after adjusting for US$40 million placement is US$88.8 million plus up to an additional US$40m from existing financing facilities, subject to certain milestones.

PDUFA = Prescription Drug User Fee Act RMAT = Regenerative Medicine Advanced Therapy

LVAD = Left Ventricular Assist Device

BLA = Biologics License Application FDA = United States Food and Drug Administration

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Late-Stage Clinical Pipeline

Based on the Proprietary Allogeneic Mesenchymal Stromal Cell Platform

Product	Indication	Phase 2	Phase 3	Regulatory Filing	Approved	Status/Next Steps
Remestemcel-L Pediatric SR-aGVHD • BLA accepted for review • PDUFA goal date August 2, 2023 • FDA PLI conducted
Remestemcel-L Adult SR-aGVHD; ARDS; IBD • Label extension • Clinical collaborations • Investigator-initiated trials
Rexlemestrocel-L CLBP • RMAT granted • Planning to start pivotal Phase 3 trial mid-CY2023
Rexlemestrocel-L HFrEF • RMAT granted for End-Stage / LVAD • FDA meeting planned for CY2023

SR-aGVHD = Steroid-Refractory Acute Graft Versus Host Disease CLBP = Chronic Low Back Pain

HFrEF = Heart Failure with Reduced Ejection Fraction LVAD = Left Ventricular Assist Device ARDS = Acute Respiratory Distress Syndrome

RMAT = Regenerative Medicines Advanced Therapy designation PLI = Pre-Licensure Inspection

5 IBD = Inflammatory Bowel Disease

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for the Period Ended March 31, 2023

Manufacturing Remestemcel-L

© Lonza, reproduced with permission

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Financial Highlights

Royalty Revenue

Revenue from royalties on sales of TEMCELL® HS Inj.[1] sold in Japan by our licensee were US$1.8 million for the quarter ended March 31, 2023. On a constant currency basis, royalties on sales grew 4% quarter on quarter to US$2.0[2] million for the quarter ended March 31, 2023, compared with US$1.9 million for the quarter ended March 31, 2022. Last 12-months revenue of US$7.6 million from royalties on product sales.

Cash Burn

Net cash usage for operating activities in the third quarter FY2023 was US$16.2 million; this represented a 4% increase (US$0.7 million) on the third quarter FY2022, and a 34% reduction (US$8.3 million) on the third quarter FY2021.

Capital

Successful completion of a global private placement primarily to Mesoblast’s existing major US, UK, and Australian shareholders raising approximately US$40.0 million, net of transaction costs.

Cash Reserves

At March 31, 2023, cash-on-hand was US$48.8 million, pro-forma cash after adjusting for proceeds of US$40.0 million raised in April private placement is US$88.8 million, with up to an additional US$40.0 million available to be drawn down from existing financing facilities subject to achieving certain milestones.

1. TEMCELL[®] HS Inj. is a registered trademark of JCR Pharmaceuticals Co. Ltd.

2. TEMCELL sales by our Licensee are recorded in Japanese Yen before being translated into USD for the purposes of calculating the royalty paid to Mesoblast. Results have been adjusted for the movement of the USD to Japanese Yen exchange rate from 1USD:123.41 Yen for the 3 months ended March 31, 2022 to 1USD:134.54 Yen for the 3 months ended March 31,2023.

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Reduction in Expenditure on R&D, Improved Loss Before Tax

P&L for the quarter ended (US$m) Mar 31, 2023 Mar 31, 2022	P&L for the quarter ended (US$m) Mar 31, 2023 Mar 31, 2022	P&L for the quarter ended (US$m) Mar 31, 2023 Mar 31, 2022
Total Revenue	1.9	2.0
Research and development	(7.0)	(8.2)
Manufacturing	(6.2)	(5.6)
Management & administration	(6.4)	(7.6)
Revaluation of contingent consideration	1.3	0.7
Revaluation of warrant liability	(0.5)	0.9
Other operating income & expenses	3.3	0.4
Finance costs	(5.0)	(3.9)
Loss before tax	(18.6)	(21.3)
Income tax benefit	~	~
Loss after tax	(18.6)	(21.3)

Revenue: Revenue predominately from royalties on sales of TEMCELL[®] HS Inj.[1] sold in Japan by our licensee.

Reduction in R&D Expenditure: reduced by US$1.2 million (14%), down to US$7.0 million for the quarter ended March 31, 2023. R&D expenses primarily supported preparations for the remestemcel-L BLA re-submission and preparations for pivotal studies for rexlemestrocel-L.

Continued Investment in Manufacturing: continued manufacturing activities to support the potential commercial launch for SR-aGVHD. On FDA approval US$31.0 million of remestemcel-L pre-launch inventory will be recognized on the balance sheet.

Finance Costs include US$3.8 million of non-cash expenditure for the quarter ended March 31, 2023 comprising accruing interest and borrowing costs.

Figures have been rounded.

1. TEMCELL[®] HS Inj. is a registered trademark of JCR Pharmaceuticals Co. Ltd.

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Steroid-Refractory Acute Graft Versus Host Disease (SR-aGVHD)

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Acute Graft Versus Host Disease (aGVHD)

Serious and Fatal Complication of Allogeneic Bone Marrow Transplantation (BMT)

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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 & CD8
Tissue Macrophage input to
chemotherapy, or T-cells
Damage cytokine storm
radiation
Macrophage
Cytokine Storm
TNF, IL-1, IL-6
IFNγ, IL-2, IL-12, IL-21, IL-22, IL-23
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Modified from Blazar et al., Nature Reviews Immunology 12: 443 – 458

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Remestemcel-L: Steroid-Refractory Acute Graft Versus Host Disease (SR-aGVHD) SR-aGVHD is associated with mortality rates as high as 90%

Treatment Options Burden of Illness

Market Opportunity

Corticosteroids are first-line Acute GVHD is a lifeMore than 30,000 therapy for aGVHD threatening complication allogeneic BMTs performed that occurs in ~50% of globally (>20K US/EU) There is only one approved patients receiving allogeneic annually, ~20% pediatric[3,4] treatment for disease bone marrow transplants refractory to steroids and no Approx. 1,500 allogeneic (BMTs)[1] approved treatment in the BMTs in children and US for children under 12 Acute GVHD primarily adolescents in US[4] years old affects skin, GI tract, and liver In Japan, Mesoblast’s licensee has received the Steroid-refractory aGVHD is only product approval for associated with mortality SR-aGVHD in both children rates as high as 90%[1,5] and and adults significant extended hospital stay costs[2]

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1. Westin, J., Saliba, RM., Lima, M. (2011) Steroid-refractory acute GVHD: predictors and outcomes. Advances in Hematology. 2. Anthem-HealthCore/Mesoblast claims analysis (2016). Data on file 3. Niederwieser D, Baldomero H, Szer J. (2016) Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey. 4. HRSA Transplant Activity Report, CIBMTR, 2019 5. Axt L, Naumann A, Toennies J (2019) Retrospective single center analysis of outcome, risk factors and therapy in steroid refractory graft-versus-host disease after allogeneic hematopoietic cell transplantation. Bone Marrow Transplantation.

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Remestemcel-L for Children with SR-aGVHD

Improved Early Survival Across Three Studies involving more than 300 Treated Children

Day 100 Survival Remestemcel-L Protocol Remestemcel-L Matched Controls Matched Control Protocol First Line Therapy after Steroids Treatment Setting Pediatric Subset of Protocol 280 : 79% 54% Study Control Arm (n=13) randomized controlled P3, n=27 w/SR-aGVHD Study 001 , open-label P3, n=54[1 ] MAGIC[2] cohort , n=30[3] propensity74% 57% with 89% Grade C/D disease controlled subset Salvage Therapy Treatment Setting Expanded Access Protocol (EAP275) , n=241 66% na CIBMTR dbase , n=327[4] propensity EAP275 , n=51 Grade D subset 51% 31% controlled subset

1. GVHD001 had 55 randomized patients, however one patient dropped out before receiving any dose of remestemcel-L; 2. Mount Sinai Acute GVHD International Consortium (MAGIC) - a group of ten BMT centers throughout the US and Europe whose purpose is to conduct ground-breaking clinical trials in GVHD, including developing informative biorepositories that assist in developing treatments that can guide GVHD therapy; 3. Two subjects in the MAGIC cohort had follow-up <100 days; these subjects are excluded from the respective survival analyses; 4. Data on file

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Remestemcel-L Treatment Outcomes

Significantly Greater Survival in Highest-Risk Steroid-Refractory Patients with Baseline MAP ≥ 0.29

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Kaplan-Meier Estimates of 6-month Overall
Survival for the Two Patient Cohorts by
Baseline MAP
Abbreviations:
MAP: MAGIC algorithm probability;
BAT: best available therapy.
BAT
Remestemcel-L
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Kasikis S et al. Bone Marrow Transplantation 2021; 56:2869–2870.

Status of BLA for Remestemcel-L in Pediatric Patients with SR-aGVHD

New Data Under Review

BLA resubmitted Jan 30, 2023

BLA file considered by FDA to be a complete response, accepted for review, with PDUFA goal date August 2, 2023

New data under review shows:

• Durable long-term survival of patients in Phase 3 trial

o Increased survival in high-risk patients compared with propensity matched controls

o Positive correlation between in vitro potency assay and survival

• That the validated potency assay has low variability and can adequately demonstrate manufacturing consistency and reproducibility

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Status of BLA for Remestemcel-L in Pediatric Patients with SR-aGVHD

Manufacturing Inspection Conducted

FDA has now conducted the Pre-License Inspection (PLI) of the manufacturing process for remestemcel-L

FDA inspection did not result in the issuance of a Form 483, which is provided at the conclusion of an inspection if investigators have observed any conditions that in their judgment may constitute violations of the Food Drug and Cosmetic Act and related Acts

Establishment Inspection Report (EIR) is expected to be issued by FDA in the coming weeks providing a detailed summary and final assessment of the inspection

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Remestemcel-L: Long-Term Survival Data a Cornerstone of BLA Resubmission to FDA for SR-aGVHD

Mesoblast provided new results from a four-year observational survival study performed by the Center for International Blood and Marrow Transplant Research (CIBMTR) on 51 evaluable patients with SR-aGVHD who were enrolled in Mesoblast’s phase 3 clinical trial of remestemcel-L Overall survival in the remestemcel-L cohort was 63% at 1 year, 51% at 2 years, and 49% at 4 years

The new long-term survival data provide assurance that the short-term day 28 responses and early survival through 180 days in the 54-patient Phase 3 trial in children with SR-aGVHD previously presented to FDA in the original BLA submission are unlikely to have arisen by chance These long-term survival outcomes are a cornerstone of the BLA resubmission

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Long term Survival in Pediatric Patients with SR-aGVHD Treated with Remestemcel-L Presented at the 2023 Tandem Meeting of ASTCT and CIBMTR

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2-Year Survival in Pediatric Patients2-Year Survival in Pediatric Patients 2-Year Survival in Pediatric Patients
Treated with SteroidsRefractory to Steroids [1][1] GVHD001 [2] 2
N=370N=128 N=51
180 2
1 Days Years
0.8
69%
0.6
51%
Steroid Refractory –
0.4 Remestemcel-L
Steroid Refractory – Best
Available Therapies 0.2
0
0 6 12 18 24
Months
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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 Transplant 55, 165–171 (2020); 2.CIBMTR – Center for International Blood & Bone Marrow Transplantation Research. Clinical Outcomes of Pediatric Patients Treated with Remestemcel-L for Steroid-Refractory Acute Graft Versus-Host Disease on a Phase 3, Single- Arm, Prospective Study (Nov 2022)

ASTCT = American Society for Transplantation and Cellular Therapy; CIBMTR = Center for International Blood and Marrow Transplant Research

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Extended Survival Data in Children with SR-aGVHD

Remestemcel-L Treatment Resulted in Durable Survival Over 4 Years

Survival Outcomes in Pediatric & Adult SR-aGVHD

(Remestemcel-L data from the Center for International Blood and Marrow Transplant Research (CIBMTR) dbase)

Study	GVHD001	MacMillan et al1	Rashidi et al2	REACH23	REACH23	REACH14
Treatment	Remestemcel-L	BAT5	BAT5	BAT5	Ruxolitinib	Ruxolitinib
N=	51	128	203	155	154	71
Subjects	Children	Children	Adults	Adults	Adults	Adults
aGVHD Grade	88% Grade C/D	22% Grade 3/4	54% Grade 3/4	63% Grade 3/4	63% Grade 3/4	68% Grade 3/4
Year 1 Survival	63%	40%	--	44%	49%	43%
Year 2 Survival	51%	35%	25%	36%	38%	--
Year 3 Survival	49%
Year 4 Survival	49%

1. MacMillan ML et al. Pediatric acute GVHD: clinical phenotype and response to upfront steroids. Bone Marrow Transplant 2020; 55(1): 165-171

2. 2.Rashidi A et al. Outcomes and predictors of response in steroid-refractory acute graft-versus-host disease: single-center results from a cohort of 203 patients. Biol Blood Bone Marrow Transplant 2019; 25(11):2297-2302. 3.Zeiser R et al. Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease. N Engl J Med 2020;382:1800-10.

3. 4.Jagasia M et al. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood. 2020 May 14; 135(20): 1739–1749

4. 5.BAT = Best Available Treatment

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The Immunomodulatory Activity of Remestemcel-L on T Cell Activation in vitro is a Direct Measure of Product Potency and Correlates with Survival in Pediatric Patients with SR-aGVHD

The clinical benefits of remestemcel-L in SR-aGVHD are likely due to its immunomodulatory effects on alloreactive T cell activation/proliferation and inflammatory cytokine production

An in vitro assay measuring inhibition of T-cell activation was established during development, prior to the Phase 3 trial, as a potential measure of product potency

Assay was used to measure the ability of individual remestemcel-L lots to inhibit T cell activation prior to their use in EAP 275 and the Phase 3 trial GVHD 001

Correlations between survival outcomes in EAP 275 and the Phase 3 trial GVHD 001 and potency of lots received as measured by inhibition of T-cell activation were performed

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Correlation of Remestemcel-L (Ryoncil) Lot Potency and 6-Month Survival

Analyses were performed evaluating in vitro/in vivo relationships in relation to inhibition of T-cell activation by product lots administered

There was an association between higher inhibition of T-cell activation by product lots received and Day 180 survival (85% Day 180 OS > median vs. 54% Day 180 OS ≤ median, p=0.01)

The relationship between greater survival and level of inhibition of T-cell activation > median vs. ≤ median was most evident in patients with the most severe form of the disease and at highest risk for death:

• Minnesota high risk (Day 180 OS 89% vs 50%, p=0.01)

• MAGIC Algorithm Probability (MAP) ≥0.29 (Day 180 OS 100% vs. 17%, p=0.003)

• IBMTR Grade D disease (Day 180 OS 91% vs. 50%, p=0.03)

Note that expected Day 180 survival for Grade D treated with best available therapy in CIBMTR registry is ~30%

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Survival Significantly Improved in EAP 275 aGVHD Patients Receiving Higher Potency Ryoncil Product Made After 2008 Compared with Lower Potency Prochymal Product Made Before 2008 Greatest Effect Seen In Patients With Grade D Disease

All EAP 275 Day 100 survival (n=205): Prochymal 56% vs Ryoncil 74%, p = 0.007

Grade D EAP 275 Day 100 survival (n=106): P ~~rochymal 44% vs Ryoncil 72%~~ , p = 0.005

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Go to Market Strategy - Remestemcel-L in Pediatric Patients Pre-Launch: Engagement of Highest Transplant Volume Centers with Experience Using Ryoncil

Non-promotional activities including profiling centers, educate on disease awareness & unmet needs, and support payer engagement

Hiring of select positions to build out commercial team has commenced

Key Activities:

• Market Access initiates payer outreach

o Medical provides education to payers

o Corporate leadership initiates engagement with Top 15 centers

o Regional sales directors lead center profiling

Manufacturing preparation has been ongoing with US$31.0 million of remestemcel-L pre-launch inventory in-hand

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Go to Market Strategy - Remestemcel-L in Pediatric Patients Post-Approval Launch: Staged Approach Initially Targeting Highest Transplant Volume Centers

Staged approach to launch based on centers with highest volume and experience with product Building out efficient, targeted sales force - 15 highest volume centers account for ~50% of patients

Key Activities:

o Initiate commercial onboarding & logistics at centers

o MSLs engage centers around medical & scientific needs

o Logistical and reimbursement support offered as needed

o Center certification for remestemcel-L administration

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Chronic Low Back Pain due to Degenerative Disc Disease (CLBP)

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Chronic Low Back Pain Due to Degenerative Disc Disease (CLBP) Impacts 7M+ Rexlemestrocel-L represents a potential new paradigm for the treatment of CLBP

Burden of Illness

Treatment Options Market Opportunity

Back pain causes more Minimal treatment options disability than any other for patients with chronic low condition[1] back pain (CLBP) who fail conservative therapy include Inflicts substantial direct opioids and surgery and indirect costs on the healthcare system,[1] 50% of opioid prescriptions including excessive use of are for CLBP[2] opioids in this patient Durable improvement in population pain has potential to reduce opioid use and prevent surgical intervention

Over 7m patients are estimated to suffer from CLBP due to degenerative disc disease (DDD) in each of the U.S. and E.U.5[2-4]

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1. Williams, J., NG, Nawi, Pelzter, K. (2015) Risk factors and disability associated with low back pain in older adults in low-and middle-income countries. Results from the WHO Study on global ageing and adult health (SAGE). PloS One. 2015; 10(6): e0127880., 2.Decision Resources: Chronic Pain December 2015., 3. LEK & NCI opinion leader interviews, and secondary analysis., 4. Navigant: Commercial Assessment for a Proprietary Cell-Based Therapy for DDD in the U.S. and the EU3 – August 2014.

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Rexlemestrocel-L / CLBP – Program Summary

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----- Start of picture text -----

In Prep for US/EU Commence Pivotal P3
Regulatory Alignment Phase 3 Protocol
Submissions Mid-CY2023
Gained alignment with FDA has agreed with The planned Phase 3 RMAT designation for
the FDA on the Mesoblast plans for Program will include 80% CLBP received from FDA
mean
appropriate pivotal pain reduction of subjects in the US and February 2023
Phase 3 study at 12 months as the 20% from the EU, to
primary endpoint of support regulatory Commencement of
Seeks to replicate the the pivotal trial submissions to FDA and pivotal trial mid-CY2023
significant reduction in EMA
pain seen at 12 and 24 Functional
months in our first Phase improvement and
3 trial reduction in opioid use
as secondary endpoints
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Regenerative Medicine Advanced Therapy (RMAT) Designation Granted by FDA for Rexlemestrocel-L in the treatment of CLBP

RMAT designation provides all the benefits of Breakthrough and Fast Track designations, including rolling review and eligibility for priority review on filing of a Biologics License Application (BLA)

Results from the trial showed that:

A single injection of rexlemestrocel-L+HA into the lumbar disc resulted in significant reduction in pain compared with saline control at 12 and 24 months across all subjects (n=404)

Pain reduction through 36 months was seen in the subset of patients using opioids at baseline (n=168) with the rexlemestrocel-L+HA group having substantially greater reduction at all time points compared with saline controls

Among patients on opioids at baseline, despite instructions to maintain existing therapies throughout the trial, at 36 months 28% who received rexlemestrocel-L+HA were not taking an opioid compared with 8% of saline treated controls

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Phase 3 Trial Outcomes based on a Single Injection of Rexlemestrocel-L + HA Results in More than Three Years of Pain Reduction

Greatest pain reduction was observed in the pre-specified population of subjects with CLBP duration shorter than the baseline study median of 68 months (n=202) with significantly greater reduction (nominal p-value < 0.05) at all time points analyzed over 36 months compared with saline controls

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LS Mean VAS Change
in Low Back Pain from
Baseline - Duration
CLBP < 68 Month
Median Baseline
Duration (n=202)
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VAS=Visual Analog Score; HA=Hyaluronic Acid

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Chronic Heart Failure Reduced Ejection Fraction (HFrEF)

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Rexlemestrocel-L / HFrEF – Program Summary Defining the Regulatory Path to FDA Approval

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Significant Need Promising Data Targeting Inflammation FDA Meeting Cardiovascular disease Recent data from the Effects on LVEF and MACE Mesoblast plans to meet remains the leading DREAM-HF P3 trial outcomes are enhanced with the FDA CY2023 cause of death in the US showed improved LVEF in patients with active under its RMAT at 12 months, preceding inflammation designation to discuss CHF is a progressive long-term reduction in Trial results from class II the potential pathway to disease with a high MACE events across all approval to end-stage HFrEF now mortality approaching treated patients support a MOA by which 50% at 5 years, and at rexlemestrocel-L reverses least 75% after an initial LVEF is a potential early inflammation-related hospitalization surrogate endpoint endothelial dysfunction

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Patients Experience Progressive Vascular Dysfunction and Heart Failure Rexlemestrocel-L has the potential to improve endothelial dysfunction in patients from Class II thru IV

Mesoblast’s Development Programs

DREAM HF-1 Trial

537 Patients

LVAD MPC Studies

189 Patients

Early

Guideline Directed Medical Therapies (GDMT)

Continuum of Cardiovascular Disease Risk

DEATH

NYHA ClassI

NYHA Class II

NYHA Class IIB/IIIA NYHA Class IIIB/IV

Traditional Early Therapies for HFrEF

• Statins

• Beta blockers

• Re-vascularization or valvular surgery

• RAAS antagonists

• Diuretics for fluid retention

• Hydralazine / isosorbide dinitrate

• Digitalis

Recent New Oral Therapies for Decompensated HFrEF Hospitalizations and Fluid Overload

• sacubitril / valsartan

• SGLT2 inhibitors

• Vericiguat

NYHA Class IIB or IIIA Persistent HFrEF Patients

NYHA Class IIIB/IV Pts with end-stage HFrEF

• Cardioverter Defibrillator

• Cardioverter Defibrillator • Optimal medical (ICD) +/management

  • LVAD implantation

• CRT-D or Wearable Cardioverter Defibrillator if Indicated

• Heart transplant

• Artificial Heart

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ORIGINAL INVESTIGATIONS

Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients With Heart Failure

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Emerson C. Perin, MD, PHD,a Kenneth M. Borow, MD,b Timothy D. Henry, MD,c Farrell O. Mendelsohn, MD,d Leslie W. Miller, MD,e Elizabeth Swiggum, MD,f Eric D. Adler, MD,g David H. Chang, MD,h R. David Fish, MD,a Alain Bouchard, MD,d Margaret Jenkins, BSC (HONS),i Alex Yaroshinsky, PHD,j Jack Hayes, MA,k Olga Rutman, PHD,k Christopher W. James, PA,k Eric Rose, MD,l Silviu Itescu, MD,l Barry Greenberg, MDm

Randomized, double-blind, controlled, 537 patient Phase 3 trial of rexlemestrocel-L over mean followup of 30 months showed:

Improved LVEF from baseline to 12 months in all patients - maximal benefit seen in patients with active inflammation

Reduced risk of MI or stroke by 57% in all treated patients, and by 75% in patients with inflammation

Reduced risk for time-to-first Major Adverse Cardiac Event (MACE), defined as cardiovascular death, MI or stroke, by 28% in all patients, and by 37% in patients with inflammation

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Rexlemestrocel-L – Two Pivotal Studies in Chronic Heart Failure (CHF) Mesoblast’s Development Programs Assess the Impact of Intra-cardiac Administration of Rexlemestrocel-L Across the Continuum of Disease from Mild/Moderate to End-stage Severity

MPC Study Design	LVAD-MPC Study #2	LVAD-MPC Study #2	DREAM-HF Trial
Treated Patients	159	537
Study Design	Prospective, randomized, Multi-center, double-blinded, single dose, sham-controlled, parallel group efficacy & safety studies of allogeneic mesenchymal precursor cells (MPCs)
Pathologies of↑ed Importance	LV Systolic Function, Inflammation, Mortality, Major Morbidities
Product	Mesenchymal Precursor Cells with defined Cardiac Potency (Rexlemestrocel-L)
Cell Preparation, Manufacturing, Central Storage and Shipping	Same facilities and vendors in both studies
Physical Location Used for Cell Administration at the Study Site	Operating room		Cardiac catheterization laboratory
Patient Analysis Population	End-stage chronic HFrEF candidate for LVAD implant (NYHA Class IIIB or IV), ischemic or non-ischemic etiology (N=159: MPC=106, CTRL=53)		Chronic HFrEF (Late NYHA Class II or IIIA), ischemic or non-ischemic etiology (N=537: MPC=265, CTRL=272)
Cell Dose in MPC	150 million cells administered as 15-20 individual injections during a single procedure
Route of Cell Administration	Epicardial injection		Transendocardial injection
Target of Cell Administration	Mid-wall of left ventricle

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mesoblast

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