NEW YORK, July 08, 2024 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, announced today it has resubmitted its BLA for approval of Ryoncil® (remestemcel-L) in the treatment of children with SR-aGVHD. The filing comes after Mesoblast was informed by FDA at the end of March that, following additional consideration, the available clinical data from the Phase 3 study MSB-GVHD001 appears sufficient to support submission of th ...

NEW YORK, July 01, 2024 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today confirmed that it will file its Biologics License Application (BLA) for approval of Ryoncil® (remestemcel-L) in the treatment of children with steroidrefractory acute graft versus host disease (SR-aGVHD) with the U.S. Food and Drug Administration (FDA) next week. About Mesoblast Mesoblast (the Company) is a world leader in developing allogeneic ...

About Mesoblast Mesoblast has a strong and extensive global intellectual property portfolio with protection extending through to at least 2041 in all major markets. The Company's proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide. Mesoblast has locations in Australia, the United States and Singapore and is listed on the Austr ...

NEW YORK, June 02, 2024 (GLOBE NEWSWIRE) -- Mesoblast Limited (NASDAQ:MESO, ASX:MSB))), Chief Executive Silviu Itescu provided a corporate update at the Bell Potter Emerging Leaders Conference. Dr. Itescu reiterated that the Company expects to file this quarter the Biologics License Application (BLA) resubmission with the United States Food and Drug Administration (FDA) for its lead product candidate Ryoncil®(remestemcel-L) in the treatment of steroid-refractory acute graft versus host disease, with potenti ...

NEW YORK, April 29, 2024 (GLOBE NEWSWIRE) -- Mesoblast Limited (NASDAQ:MESO, ASX:MSB))), global leader in allogeneic cellular medicines for inflammatory diseases, today provided an activity report for the third quarter ended March 31, 2024. Mesoblast Chief Executive Silviu Itescu said: "We are very pleased with the positive interactions we had last quarter with the FDA, having received clarity on the path to licensure for our product candidates in pediatric acute graft versus host disease and in ischemic pa ...

[Company Overview](index=4&type=section&id=Company%20Overview) [Investment Highlights](index=4&type=section&id=Investment%20Highlights) Mesoblast is developing a portfolio of allogeneic (off-the-shelf) cellular medicines for inflammatory diseases, with key late-stage assets Remestemcel-L and Rexlemestrocel-L having completed Phase 3 trials and received FDA RMAT designations - Developing off-the-shelf, allogeneic cellular medicines based on mesenchymal stromal cell (MSC) technology, eliminating the need for donor matching[8](index=8&type=chunk) - Remestemcel-L has completed a pivotal Phase 3 trial for pediatric Steroid-Refractory Graft v Host Disease (SR-aGVHD) and is collaborating with the Bone Marrow Transplant Clinical Trials Network (BMT CTN) for a pivotal trial in the larger adult SR-aGVHD market[8](index=8&type=chunk) - Rexlemestrocel-L has completed Phase 3 trials for both heart failure with reduced ejection fraction (HFrEF) and chronic low back pain (CLBP), with Regenerative Medicine Advanced Therapy (RMAT) designation granted for both indications[8](index=8&type=chunk) [Global Intellectual Property (IP) Estate](index=5&type=section&id=Global%20Intellectual%20Property%20%28IP%29%20Estate) The company holds a robust global intellectual property portfolio, providing a significant competitive advantage with over 1,100 patents and applications extending through 2040, covering composition of matter, manufacturing, and therapeutic applications, and successfully monetized through royalty and licensing agreements - Extensive patent portfolio with over **1,100 patents and patent applications** across 82 patent families, with protection extending through **2040**[9](index=9&type=chunk) - IP portfolio provides strong global protection for core commercial focus areas and enables out-licensing opportunities in non-core areas[9](index=9&type=chunk) - Demonstrated track record of IP management through a royalty agreement with JCR Pharmaceuticals in Japan and a patent license granted to Takeda's subsidiary, TiGenix[9](index=9&type=chunk) [Manufacturing and Platform Technology](index=6&type=section&id=Manufacturing%20and%20Platform%20Technology) Mesoblast has established a commercial-scale, scalable allogeneic manufacturing process that meets international regulatory standards, ensuring batch-to-batch consistency, with its underlying platform technology utilizing mesenchymal precursor/stromal cells activated by inflammatory cytokines to orchestrate an anti-inflammatory response, forming the basis for its late-stage clinical pipeline - Manufacturing process is scalable for "off-the-shelf" products and meets stringent criteria of international regulatory agencies[12](index=12&type=chunk) - Manufacturing innovations include proprietary xeno-free technologies, scaled-up 2D manufacturing, and 3D bioreactors to increase capacity and reduce cost of goods[12](index=12&type=chunk) Late-Stage Clinical Pipeline | Product | Indication | Phase 2 | Phase 3 | Regulatory Filing | | :--- | :--- | :--- | :--- | :--- | | Remestemcel-L | Pediatric SR-aGVHD | | >> | >> | | Remestemcel-L | Adult SR-aGVHD Crohn's | | >> | | | Rexlemestrocel-L | HFrEF | | >> | | | Rexlemestrocel-L | CLBP | | >> | | [Clinical Programs & Milestones](index=9&type=section&id=Clinical%20Programs%20%26%20Milestones) [2024 Clinical Program Milestones](index=9&type=section&id=2024%20Clinical%20Program%20Milestones) Mesoblast has outlined key clinical and regulatory milestones for 2024, focusing on advancing its late-stage pipeline, including FDA meetings for RYONCIL® potency data and the HFrEF approval pathway, commencement of an adult SR-aGVHD trial, and start-up activities for the Phase 3 CLBP trial Key 2024 Milestones | Program | Milestone | Target | | :--- | :--- | :--- | | **RYONCIL (remestemcel-L)** | FDA meeting regarding potency assay data for pediatric BLA | Q1 CY24 | | | Commence patient enrollment for adult SR-aGVHD trial | Q2 CY24 | | **REVASCOR (rexlemestrocel-L)** | Meet with FDA under RMAT to discuss approval pathway in adults with HFrEF | Q1 CY24 | | | Meet with FDA on congenital heart disease pathway to approval in pediatrics | Q2 CY24 | | **Inflammatory Pain (rexlemestrocel-L)** | CLBP Phase 3 trial start-up activities | Q4 FY24 | | | Phase 3 CLBP patient screening/enrollment initiates | Q1-Q2 CY25 | [Remestemcel-L for Steroid-Refractory Acute Graft Versus Host Disease (SR-aGVHD)](index=10&type=section&id=Remestemcel-L%20for%20SR-aGVHD) The Remestemcel-L (RYONCIL®) program targets SR-aGVHD, a life-threatening complication of bone marrow transplants with high mortality, advancing regulatory discussions with the FDA for the pediatric indication and initiating a Phase 3 trial for the larger adult SR-aGVHD market [Market Opportunity & Disease Overview](index=18&type=section&id=Market%20Opportunity%20%26%20Disease%20Overview) Acute Graft Versus Host Disease (aGVHD) is a severe complication of allogeneic bone marrow transplants (BMT), affecting about 50% of patients, with the steroid-refractory form (SR-aGVHD) having mortality rates as high as 90%, representing a significant unmet medical need in a global market of over 30,000 allogeneic BMTs annually with limited approved treatment options - aGVHD is a life-threatening complication occurring in **~50% of patients** receiving allogeneic BMTs, with SR-aGVHD mortality rates reaching as high as **90%**[35](index=35&type=chunk) - The market opportunity includes over **30,000 allogeneic BMTs** performed globally each year, with approximately **9,000-10,000** in the US[35](index=35&type=chunk) - There is only one approved treatment for steroid-refractory disease in the US and no approved treatment for children under 12[35](index=35&type=chunk) [Pediatric SR-aGVHD Clinical Data & Regulatory Status](index=20&type=section&id=Pediatric%20SR-aGVHD%20Clinical%20Data%20%26%20Regulatory%20Status) Clinical data for Remestemcel-L in pediatric SR-aGVHD shows consistently improved survival rates and durable long-term benefits over 4 years compared to historical controls, with Mesoblast having submitted new potency assay data to the FDA and a meeting scheduled in March 2024 to discuss the product's path to approval, as the new data indicates the current product is more potent, potentially explaining its greater impact on survival - An FDA meeting is scheduled for **March 2024** to review new potency assay data for RYONCIL, which shows the current product is more potent than earlier versions[19](index=19&type=chunk)[42](index=42&type=chunk) Long-Term Survival in Pediatric SR-aGVHD (Study GVHD001, N=51) | Time Period | Survival Rate (Remestemcel-L) | Survival Rate (Best Available Therapies¹) | | :--- | :--- | :--- | | Year 1 | 63% | 40% | | Year 2 | 51% | 35% | | Year 4 | 49% | N/A | [Adult SR-aGVHD Development Pathway](index=11&type=section&id=Adult%20SR-aGVHD%20Development%20Pathway) Mesoblast is expanding its SR-aGVHD program to adults, a market approximately five times larger than the pediatric segment, by collaborating with the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) to conduct a pivotal Phase 3 trial targeting a high-need population of adults and adolescents refractory to both corticosteroids and a second-line agent like ruxolitinib, for whom there are no approved therapies and survival is as low as 20-30% at 100 days - The adult SR-aGVHD market is approximately **5-fold larger** than the pediatric market[21](index=21&type=chunk)[45](index=45&type=chunk) - A Phase 3 trial will be conducted in collaboration with BMT CTN, which is responsible for **~80% of all US transplants**[21](index=21&type=chunk)[45](index=45&type=chunk) - The trial will target patients who have failed both corticosteroids and a second-line agent (e.g., ruxolitinib), a population with 100-day survival rates as low as **20-30%**[21](index=21&type=chunk)[45](index=45&type=chunk) [Rexlemestrocel-L for Heart Disease](index=12&type=section&id=Rexlemestrocel-L%20for%20Heart%20Disease) The Rexlemestrocel-L (REVASCOR®) program is being advanced for two distinct heart disease indications: for adults with chronic heart failure (HFrEF), Mesoblast is in discussions with the FDA under an RMAT designation to define a regulatory pathway based on positive Phase 3 data, and for pediatric congenital heart disease, the product has received Rare Pediatric Disease and Orphan Drug designations following a successful randomized controlled trial, creating a potential path to a Priority Review Voucher upon approval [Chronic Heart Failure (HFrEF) in Adults](index=12&type=section&id=Chronic%20Heart%20Failure%20%28HFrEF%29%20in%20Adults) In the Phase 3 DREAM-HF trial of 537 patients, a single treatment of Rexlemestrocel-L demonstrated a reduction in major adverse cardiac events (MACE), particularly in patients with active inflammation, and Mesoblast has met with the FDA under its RMAT designation to discuss potential approval pathways for high-risk HFrEF patients with inflammation, with meeting minutes expected shortly - Met with the FDA in **Q1 CY2024** under RMAT designation to discuss potential pathways to approval for HFrEF patients with inflammation[22](index=22&type=chunk) - The **537-patient Phase 3 DREAM-HF trial** showed a single injection of rexlemestrocel-L reduced the risk of MI or stroke by **57%** in all patients and by **75%** in patients with inflammation[53](index=53&type=chunk) - Time-to-first MACE (cardiovascular death, MI, or stroke) was reduced by **28%** in all patients and by **37%** in patients with inflammation[53](index=53&type=chunk) [Pediatric Congenital Heart Disease](index=13&type=section&id=Pediatric%20Congenital%20Heart%20Disease) REVASCOR® has been granted both Rare Pediatric Disease Designation (RPDD) and Orphan Drug Designation (ODD) by the FDA for treating Hypoplastic Left Heart Syndrome (HLHS), a life-threatening congenital condition, with a randomized controlled trial showing that a single injection significantly increased left ventricle growth, potentially enabling a more successful surgical correction, and approval for this indication could make Mesoblast eligible for a valuable Priority Review Voucher (PRV) - FDA granted REVASCOR **Rare Pediatric Disease Designation (RPDD)** and **Orphan Drug Designation (ODD)** for Hypoplastic Left Heart Syndrome (HLHS)[23](index=23&type=chunk)[24](index=24&type=chunk) - A randomized controlled trial published in JTCVS Open showed a single intramyocardial injection of REVASCOR resulted in significantly increased left ventricle growth over **12 months** compared to control[24](index=24&type=chunk)[56](index=56&type=chunk) - Upon potential BLA approval, Mesoblast may be eligible to receive a **Priority Review Voucher (PRV)**, which can be sold or used to accelerate review of a future drug[59](index=59&type=chunk) [Rexlemestrocel-L for Chronic Low Back Pain (CLBP)](index=31&type=section&id=Rexlemestrocel-L%20for%20Chronic%20Low%20Back%20Pain%20%28CLBP%29) Mesoblast is advancing Rexlemestrocel-L for chronic low back pain (CLBP) due to degenerative disc disease, a condition affecting over 7 million patients in the U.S. and E.U., having gained alignment with the FDA for a pivotal Phase 3 trial using mean pain reduction at 12 months as the primary endpoint, following a prior Phase 3 trial where a single injection provided durable pain reduction for up to 36 months and showed potential to reduce opioid use [Market Opportunity & Program Summary](index=32&type=section&id=Market%20Opportunity%20%26%20Program%20Summary) CLBP represents a major market opportunity with over 7 million estimated patients in both the U.S. and E.U. who have failed conservative therapy, and Mesoblast has aligned with the FDA on a pivotal Phase 3 study design, with mean pain reduction at 12 months as the primary endpoint and functional improvement and opioid reduction as secondary endpoints, with product manufactured for the trial - The target market is estimated at over **7 million patients** in the U.S. and E.U. each suffering from CLBP due to degenerative disc disease[63](index=63&type=chunk) - Gained alignment with the FDA for a pivotal Phase 3 study, which will seek to replicate significant pain reduction seen in the first Phase 3 trial[65](index=65&type=chunk) - The pivotal trial's primary endpoint will be mean pain reduction at **12 months**, with secondary endpoints including functional improvement and reduction in opioid use[65](index=65&type=chunk) [Clinical Trial Results & Regulatory Status](index=34&type=section&id=Clinical%20Trial%20Results%20%26%20Regulatory%20Status) Rexlemestrocel-L has received RMAT designation from the FDA for CLBP, with results from the first Phase 3 trial (n=404) showing that a single injection resulted in significant and durable pain reduction at 12, 24, and 36 months, with an even more pronounced effect in a pre-specified subgroup with shorter disease duration, and demonstrated a potential for reducing opioid use, with 28% of treated patients on opioids at baseline stopping them by 36 months, versus 8% of controls - FDA granted **Regenerative Medicine Advanced Therapy (RMAT)** designation for rexlemestrocel-L in the treatment of CLBP[67](index=67&type=chunk) - A single injection resulted in significant pain reduction at **12 and 24 months** across all **404 subjects** in the first Phase 3 trial[67](index=67&type=chunk) - Among patients on opioids at baseline, **28%** receiving rexlemestrocel-L+HA were no longer taking opioids at **36 months**, compared to **8%** of saline controls[67](index=67&type=chunk) [Financial Performance](index=14&type=section&id=Financial%20Performance) [Financial Highlights (Half-Year Ended Dec 31, 2023)](index=15&type=section&id=Financial%20Highlights%20%28H1%20FY2024%29) For the half-year ended December 31, 2023, Mesoblast strengthened its financial position with US$77.6 million in cash-on-hand, demonstrating improved operational efficiency by significantly reducing its net cash usage for operating activities by 33% compared to the prior corresponding period and cutting its loss after tax by 21% Key Financial Metrics (as of Dec 31, 2023) | Metric | Value / Change | Period | | :--- | :--- | :--- | | Cash-on-hand | US$77.6 million | At Dec 31, 2023 | | Net Cash Usage (Operating) | US$26.0 million (33% reduction YoY) | Six months ended Dec 31, 2023 | | Loss After Tax | Reduced by 21% YoY | Six months ended Dec 31, 2023 | [Income Statement Analysis (Half-Year Ended Dec 31, 2023)](index=16&type=section&id=Income%20Statement%20Analysis%20%28H1%20FY2024%29) For the six months ended December 31, 2023, Mesoblast reported total revenue of US$3.4 million, primarily from royalties, and achieved a 21% reduction in loss after tax to US$32.5 million, driven by significant cost reductions in manufacturing (down 48%), R&D (down 6%), and management & administration (down 14%) compared to the same period in the prior year P&L for the six months ended (US$m) | P&L Item | Dec 31, 2023 | Dec 31, 2022 | | :--- | :--- | :--- | | Total Revenue | 3.4 | 3.4 | | Research and development | (12.6) | (13.4) | | Manufacturing | (6.7) | (12.8) | | Management & administration | (11.5) | (13.3) | | Loss before tax | (32.6) | (41.5) | | Loss after tax | (32.5) | (41.4) | - Revenue of **$3.4M** was predominantly from royalties on sales of TEMCELL® HS Inj. in Japan[27](index=27&type=chunk) - Manufacturing expenditure was significantly reduced by **48%** to **$6.7 million** from **$12.8 million** in the comparative period[27](index=27&type=chunk)

[Introduction & Company Overview](index=1&type=section&id=Introduction%20%26%20Company%20Overview) Mesoblast's mission, late-stage pipeline, and investment highlights cover its cell therapy platform and financial position [Cautionary Note Regarding Forward-Looking Statements](index=2&type=section&id=CAUTIONARY%20NOTE%20REGARDING%20FORWARD-LOOKING%20STATEMENTS) This section cautions that forward-looking statements are subject to risks and uncertainties, advising readers not to unduly rely on them as the company is not obligated to update them - The presentation contains forward-looking statements regarding future events and financial performance, which involve **known and unknown risks and uncertainties**[5](index=5&type=chunk) - Readers should not place undue reliance on these statements, and the company is not obligated to publicly update or revise any forward-looking statements[5](index=5&type=chunk) [Our Mission](index=3&type=section&id=Our%20Mission) Mesoblast's mission is to commercialize innovative cellular therapies for serious and life-threatening illnesses - Mesoblast is committed to commercializing **innovative cellular therapies** for serious and life-threatening illnesses[6](index=6&type=chunk) [Late-Stage Clinical Pipeline](index=4&type=section&id=Late-Stage%20Clinical%20Pipeline) Mesoblast's late-stage pipeline leverages its allogeneic mesenchymal stromal cell platform, with Remestemcel-L and Rexlemestrocel-L in Phase 3 or regulatory filing stages, supported by licensing agreements | Product | Indication | Phase 3 | Regulatory Filing | | :--- | :--- | :--- | :--- | | Remestemcel-L | Pediatric SR-aGVHD | | >> | | Remestemcel-L | Adult SR-aGVHD | >> | | | Rexlemestrocel-L | CLBP | >> | | | Rexlemestrocel-L | HFrEF | >> | | - JCR Pharmaceuticals Co., Ltd. holds rights to develop **mesenchymal stromal cells (MSCs)** in certain fields for the Japanese market, including Graft vs Host Disease and hypoxic ischemic encephalopathy (HIE)[7](index=7&type=chunk) - Grünenthal has an **exclusive license** for rexlemestrocel-L for chronic low back pain in Europe and Latin America/Caribbean, while Tasly Pharmaceuticals holds **exclusive rights** for rexlemestrocel-L for chronic heart failure in China[8](index=8&type=chunk) [Investment Highlights](index=5&type=section&id=Investment%20Highlights) Key investment highlights include Mesoblast's allogeneic cell therapy platform, lead products Remestemcel-L and Rexlemestrocel-L in advanced clinical stages, and a financial position with US$7.5 million revenue and US$71.3 million cash-on-hand - Mesoblast is developing **off-the-shelf, allogeneic cellular medicines** based on proprietary mesenchymal stromal cell (MSC) technology platforms, eliminating the need for donor matching or immunosuppression[10](index=10&type=chunk) - Remestemcel-L is the **lead indication** for children with steroid-refractory acute graft versus host disease (SR-aGVHD), with an upcoming Type A meeting with the FDA to discuss product approval strategy[10](index=10&type=chunk) - Rexlemestrocel-L has completed its first **Phase 3 trial** for discogenic chronic low back pain (CLBP) and for heart failure with reduced ejection fraction (HFrEF) in Class II/III patients, with **RMAT granted by FDA** for end-stage HFrEF patients[10](index=10&type=chunk) | Metric | Value (US$) | | :--- | :--- | | Last 12 months revenue | 7.5 million | | Cash-on-hand (June 30, 2023) | 71.3 million | [Remestemcel-L for Steroid-Refractory Acute Graft Versus Host Disease (SR-aGVHD)](index=6&type=section&id=Remestemcel-L%20for%20Steroid-Refractory%20Acute%20Graft%20Versus%20Host%20Disease%20(SR-aGVHD)) Remestemcel-L's regulatory status and clinical data for pediatric and adult SR-aGVHD are detailed, showing improved survival potential [Regulatory Status for Pediatric SR-aGVHD](index=6&type=section&id=Regulatory%20Status%20for%20Remestemcel-L%20in%20Pediatric%20Patients%20with) The FDA issued a complete response for remestemcel-L's pediatric SR-aGVHD BLA, prompting Mesoblast to schedule a Type A meeting to discuss additional potency assay and adult clinical data - FDA provided a **complete response** to the BLA for remestemcel-L for pediatric SR-aGVHD, requiring demonstration of product similarity between trial and commercial product[12](index=12&type=chunk) - FDA indicated an additional clinical trial would be needed, but Mesoblast proposes providing **additional potency assay data** to establish the link[12](index=12&type=chunk) - A **Type A meeting** with FDA is scheduled for mid-September to discuss providing additional potency assay data and new clinical trial data in adults, which could support the pediatric indication[12](index=12&type=chunk) [Regulatory Status for Adult SR-aGVHD](index=7&type=section&id=Regulatory%20Status%20for%20Remestemcel-L%20in%20Patients%20with%20SR-aGVHI) Mesoblast plans a controlled study for adult SR-aGVHD, a larger market, following promising 63% 100-day survival rates in compassionate access patients, with discussions ongoing with BM CTN - Mesoblast intends to conduct a **targeted, controlled study** in adults with high mortality risk SR-aGVHD, a market approximately **5-fold larger** than children, as part of its commercial strategy[14](index=14&type=chunk) - **100-day survival** was **63%** after remestemcel-L treatment under compassionate access in **71 patients** aged 12 and older with SR-aGVHD who failed at least one additional agent, compared to **20-30%** for those failing agents like ruxolitinib[14](index=14&type=chunk) - Mesoblast is in discussions with world-leading investigators at the **Blood and Marrow Transplant Clinical Trials Network (BM CTN)** to conduct this clinical trial, with costs expected to be covered by planned spending[14](index=14&type=chunk) [Acute Graft Versus Host Disease (aGVHD) Overview](index=13&type=section&id=Acute%20Graft%20Versus%20Host%20Disease%20(aGVHD)) Acute GVHD is a severe, often fatal complication of bone marrow transplants, with SR-aGVHD having high mortality and limited treatment options, especially for children in the US - **Acute GVHD** is a **life-threatening complication** occurring in **~50%** of patients receiving allogeneic BMTs, primarily affecting skin, GI tract, and liver[26](index=26&type=chunk) - **Steroid-refractory aGVHD** is associated with **mortality rates as high as 90%** and significant extended hospital stay costs[26](index=26&type=chunk) - There is only **one approved treatment** for steroid-refractory disease and **no approved treatment in the US for children under 12 years old**; Mesoblast's licensee has the only product approval for SR-aGVHD in Japan for both children and adults[26](index=26&type=chunk) [Remestemcel-L for Children with SR-aGVHD](index=15&type=section&id=Remestemcel-L%20for%20Children%20with%20SR-aGVHD) Remestemcel-L shows improved early and durable survival in children with SR-aGVHD, with 100-day survival rates of 66-79% and 49% survival at 3-4 years | Remestemcel-L Protocol | Remestemcel-L Day 100 Survival | Matched Controls Day 100 Survival | | :--- | :--- | :--- | | Pediatric Subset of Protocol 280 (P3, n=27) | 79% | 54% | | Study 001 (P3, n=54) | 74% | 57% | | Expanded Access Protocol (EAP275, n=241) | 66% | na | | EAP275 (Grade D subset, n=51) | 51% | 31% | | Study | Year 1 Survival | Year 2 Survival | Year 3 Survival | Year 4 Survival | | :--- | :--- | :--- | :--- | :--- | | GVHD001 (Children) | 63% | 51% | 49% | 49% | [Remestemcel-L for Adults with SR-aGVHD](index=17&type=section&id=Remestemcel-L%20for%20Adults%20with%20SR-aGVHD) Mesoblast plans to expand Remestemcel-L to adult SR-aGVHD patients, a larger market, citing 63% 100-day survival in compassionate care, significantly exceeding standard treatments - The commercial strategy is to progress Remestemcel-L to adults who have failed steroids and a first-line agent, including ruxolitinib, as this market opportunity is approximately **five times larger** than the pediatric one[29](index=29&type=chunk) - **Survival** in adults with SR-aGVHD who have failed at least one additional agent, such as ruxolitinib, is **20-30%** by **100 days**, whereas **100-day survival** was **63%** after remestemcel-L treatment under compassionate care in similar patients[29](index=29&type=chunk) - Mesoblast is in discussions with world-leading investigators at the Blood and Marrow Transplant Clinical Trials Network (BM CTN) to conduct a clinical trial in adults, with the costs expected to be covered by planned spending[29](index=29&type=chunk) [Rexlemestrocel-L for Chronic Low Back Pain Due to Degenerative Disc Disease (CLBP)](index=18&type=section&id=Rexlemestrocel-L%20for%20Chronic%20Low%20Back%20Pain%20Due%20to%20Disc%20Disease%20(CLBP)) Rexlemestrocel-L's development for CLBP is detailed, including regulatory status, Phase 3 outcomes, and its potential for this unmet medical need [Chronic Low Back Pain Due to Degenerative Disc Disease (CLBP) Overview](index=19&type=section&id=Chronic%20Low%20Back%20Pain%20Due%20to%20Degenerative%20Disc%20Disease%20(CLBP)) CLBP from degenerative disc disease is a major cause of disability and opioid use, with Rexlemestrocel-L offering a new therapeutic option for over 7 million patients in the U.S. and E.U - Back pain causes **more disability** than any other condition, inflicting substantial direct and indirect costs on the healthcare system, including **excessive use of opioids**[31](index=31&type=chunk) - Minimal treatment options exist for CLBP patients who fail conservative therapy, with **50% of opioid prescriptions** being for CLBP[31](index=31&type=chunk) - Over **7 million patients** are estimated to suffer from CLBP due to degenerative disc disease (DDD) in the U.S. and E.U., representing a **significant market opportunity**[31](index=31&type=chunk) [Rexlemestrocel-L / CLBP - Program Summary](index=20&type=section&id=Rexlemestrocel-L%20%2F%20CLBP%20-%20Program%20Summary) Mesoblast has FDA alignment for a pivotal Phase 3 CLBP study of Rexlemestrocel-L, targeting pain reduction, functional improvement, and reduced opioid use, with manufacturing in place - Mesoblast gained **alignment with the FDA** on the appropriate pivotal **Phase 3 study**, with **mean pain reduction at 12 months** as the primary endpoint[33](index=33&type=chunk) - The product has been manufactured for use in the pivotal Phase 3 study, and **potency assays are in place** for product release[33](index=33&type=chunk) - The program seeks to replicate the **significant reduction in pain** seen at **12 and 24 months** in the first Phase 3 trial, with **functional improvement** and **reduction in opioid use** as secondary endpoints[33](index=33&type=chunk) [RMAT Designation and Phase 3 Trial Outcomes](index=21&type=section&id=Regenerative%20Medicine%20Advanced%20Therapy%20(RMAT)%20Designation%20(FDA%20for%20Rexlemestrocel-L%20in%20the%20treatment%20of%20CLBP)) Rexlemestrocel-L received FDA RMAT designation for CLBP, with Phase 3 trials showing significant and sustained pain reduction, especially in opioid users, and a notable reduction in opioid dependence - Rexlemestrocel-L received **Regenerative Medicine Advanced Therapy (RMAT) designation** from the FDA for CLBP, providing all the benefits of Breakthrough and Fast Track designations[35](index=35&type=chunk) - 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)[35](index=35&type=chunk) - Among patients on opioids at baseline, **28%** who received rexlemestrocel-L+HA were not taking an opioid at **36 months**, compared with **8%** of saline-treated controls[35](index=35&type=chunk) - The **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 over **36 months** compared with saline controls[36](index=36&type=chunk) [Rexlemestrocel-L for Chronic Heart Failure with Reduced Ejection Fraction (HFrEF)](index=23&type=section&id=Rexlemestrocel-L%20for%20Chronic%20Heart%20Failure%20Reduced%20Ejection%20Fraction%20(HFrEF)) Rexlemestrocel-L's HFrEF development, clinical results, and potential to improve vascular function and reduce MACE are presented [Rexlemestrocel-L / HFrEF - Program Summary](index=24&type=section&id=Rexlemestrocel-L%20%2F%20HFrEF%20-%20Program%20Summary) Rexlemestrocel-L is developed for HFrEF, addressing a critical unmet need, with DREAM-HF Phase 3 data showing improved LVEF and reduced MACE, especially in inflamed patients - **Cardiovascular disease** remains the **leading cause of death** in the US, and Chronic Heart Failure (CHF) is a progressive disease with high mortality[40](index=40&type=chunk) - Recent data from the **DREAM-HF Phase 3 trial** showed **improved LVEF at 12 months**, preceding long-term reduction in MACE events across all treated patients[40](index=40&type=chunk) - Effects on LVEF and MACE outcomes are enhanced in patients with active inflammation, supporting a mechanism of action by which rexlemestrocel-L reverses **inflammation-related endothelial dysfunction**[40](index=40&type=chunk) [Patients Experience Progressive Vascular Dysfunction and Heart](index=25&type=section&id=Patients%20Experience%20Progressive%20Vascular%20Dysfunction%20and%20Hear) Rexlemestrocel-L has the potential to improve endothelial dysfunction across HFrEF stages (NYHA Class II-IV), offering a novel therapeutic approach for cardiovascular disease - Rexlemestrocel-L has the potential to improve **endothelial dysfunction** in patients with NYHA Class II thru IV HFrEF[41](index=41&type=chunk) - Mesoblast's development program targets patients across the **continuum of cardiovascular disease**, from those on traditional early therapies to those with end-stage HFrEF requiring advanced interventions like LVAD or heart transplant[41](index=41&type=chunk)[42](index=42&type=chunk) [Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy](index=26&type=section&id=Randomized%20Trial%20of%20Targeted%20Transendocardial%20Mesenchymal%20Precursor%20Cell%20Therapy%20in%20Patients%20With%20Heart%20Failure) The DREAM-HF Phase 3 trial showed rexlemestrocel-L improved LVEF and significantly reduced MI, stroke, and MACE risks, particularly in HFrEF patients with active inflammation - **Improved LVEF** from baseline to **12 months** in all patients, with maximal benefit seen in patients with active inflammation[45](index=45&type=chunk) - **Reduced risk of MI or stroke** by **57%** in all treated patients, and by **75%** in patients with inflammation[45](index=45&type=chunk) - **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[45](index=45&type=chunk) [Two Pivotal Studies in Chronic Heart Failure](index=27&type=section&id=Rexlemestrocel-L%20-%20Two%20Pivotal%20Studies%20in%20Chronic%20Heart%20Failure) Mesoblast is conducting two pivotal studies for Rexlemestrocel-L in HFrEF, targeting both end-stage and chronic patients, using consistent manufacturing and intra-cardiac administration | Study | Patient Population | Cell Dose | Route of Administration | | :--- | :--- | :--- | :--- | | MPC Study | End-stage chronic HFrEF (NYHA Class IIIB or IV) candidate for LVAD implant | 150 million cells | Epicardial injection | | DREAM-HF Study | Chronic HFrEF (NYHA Class II/III) | Not specified in table | Transendocardial | - Both pivotal studies utilize **Mesenchymal Precursor Cells (Rexlemestrocel-L)** with defined Cardiac Potency, employing the same facilities and vendors for cell preparation, manufacturing, central storage, and shipping[46](index=46&type=chunk) - The development programs assess the impact of **intra-cardiac administration** of Rexlemestrocel-L across the continuum of disease from mild/moderate to end-stage HFrEF[46](index=46&type=chunk) [Financial Results and Outlook](index=8&type=section&id=Financial%20Results%20and%20Outlook) Mesoblast's financial performance, including revenue, cash usage, and expenditures, is presented alongside its cost containment plan [Financial Highlights for the Year](index=9&type=section&id=Financial%20Highlights%20for%20the%20Year) Mesoblast reported US$7.5 million in royalty revenue, a 4% reduction in net operating cash usage to US$63.3 million, and US$71.3 million cash-on-hand at June 30, 2023 | Metric | FY2023 (US$ million) | FY2022 (US$ million) | Change | | :--- | :--- | :--- | :--- | | Royalty Revenue | 7.5 | 8.7 | -13.79% | | Net cash usage for operating activities | 63.3 | 65.9 | -4% (reduction) | | Cash-on-hand (June 30, 2023) | 71.3 | | | - **Royalty revenue** from sales of TEMCELL® HS Inj. in Japan by the licensee was **US$8.1 million** for FY2023 on a constant currency basis, compared with **US$8.7 million** for FY2022[16](index=16&type=chunk)[17](index=17&type=chunk) - At June 30, 2023, **cash-on-hand** was **US$71.3 million**, with up to an additional **US$40 million** available from existing financing facilities, subject to certain milestones and extension[16](index=16&type=chunk) [Reduction in Expenditure on R&D, Improved Loss Before Tax](index=10&type=section&id=Reduction%20in%20Expenditure%20on%20R%26D%2C%20Improved%20Loss%20Before%20Tax) Mesoblast reduced its loss before tax to US$82.1 million, driven by a 17% decrease in R&D and a 10% decrease in manufacturing expenditure, despite a decline in total revenue | Metric | June 30, 2023 (US$m) | June 30, 2022 (US$m) | Change (US$m) | | :--- | :--- | :--- | :--- | | Total Revenue | 7.5 | 10.2 | -2.7 | | Research and development | (27.2) | (32.8) | 5.6 | | Manufacturing | (27.7) | (30.8) | 3.1 | | Management & administration | (25.4) | (27.2) | 1.8 | | Loss before tax | (82.1) | (91.6) | 9.5 | | Loss after tax | (81.9) | (91.4) | 9.5 | - **Reduction in R&D expenditure** by **US$5.6 million (17%)** to **US$27.2 million**, primarily supporting preparations for BLA re-submission and pivotal trials for rexlemestrocel-L[18](index=18&type=chunk) - **Reduction in Manufacturing expenditure** by **US$3.1 million (10%)** to **US$27.7 million**, reflecting completion of launch manufacturing activities[19](index=19&type=chunk) [Cost Containment Plan for Next 12 Months](index=11&type=section&id=Cost%20Containment%20Plan%20for%20Next%2012%20Months) Mesoblast targets a 23% reduction (US$15 million) in FY2024 net operating cash spend to US$48.3 million, achieved through reduced spending and a 40% annualized payroll cut - **Targeted 23% reduction (US$15 million)** in annual net operating cash spend from **US$63.3 million** in FY2023 to **US$48.3 million** in FY2024[21](index=21&type=chunk) - This **reduction** is achieved through decreased spend across research, sales & marketing, commercial, and payroll, partially offset by investment in Phase 3 programs for SR-aGVHD and CLBP[21](index=21&type=chunk) - A **40% annualized reduction in payroll** by February 2024, including deferred FY23 short-term incentives for all employees, and voluntary salary reductions/deferred cash payments for CEO, CMO, and Non-Executive Directors, who will receive **long-term non-cash incentives** instead[21](index=21&type=chunk) - Shift from quarterly to half-yearly reporting of Financial Statements from FY2024, with continued quarterly cash and operational reports, in line with ASX-listed entities[21](index=21&type=chunk)

Mesoblast Limited (NASDAQ:MESO) Q4 2023 Results Conference Call August 30, 2023 6:30 PM ET Company Participants Dr. Silviu Itescu - Chief Executive Officer Dr. Eric Rose - Chief Medical Officer Andrew Chaponnel - Interim Chief Financial Officer Dr. Philip Krause - Board Member Conference Call Participants Louise Chen - Cantor Edward Tenthoff - Piper Sandler Sami Corwin - William Blair John Hester - Bell Potter Operator Hello and welcome to the Mesoblast Financial Results for the Period Ended June 30, 2023. ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 ______________________________ FORM 20-F ______________________________ o REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934 OR x ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended June 30, 2023 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 OR o SHELL COMPANY REPORT PUR ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 ________________________________________ Form 6-K ________________________________________ Report of Foreign Private Issuer Pursuant to Rule 13a-16 or 15d-16 under the Securities Exchange Act of 1934 Filed in the month of May 2023 for the period ended March 31, 2023 Commission File Number 001-37626 ________________________________________ Mesoblast Limited (Exact name of Registrant as specified in its charter) ________ ...