Mesoblast (MESO) - 2024 Q2 - Quarterly Report

Company Overview Investment Highlights 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] - 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] - 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] Global Intellectual Property (IP) Estate 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] - IP portfolio provides strong global protection for core commercial focus areas and enables out-licensing opportunities in non-core areas[9] - 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] Manufacturing and Platform Technology 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] - Manufacturing innovations include proprietary xeno-free technologies, scaled-up 2D manufacturing, and 3D bioreactors to increase capacity and reduce cost of goods[12] 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 2024 Clinical Program Milestones 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) 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 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] - The market opportunity includes over 30,000 allogeneic BMTs performed globally each year, with approximately 9,000-10,000 in the US[35] - There is only one approved treatment for steroid-refractory disease in the US and no approved treatment for children under 12[35] Pediatric SR-aGVHD Clinical Data & Regulatory Status 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][42] 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 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][45] - A Phase 3 trial will be conducted in collaboration with BMT CTN, which is responsible for ~80% of all US transplants[21][45] - 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][45] Rexlemestrocel-L for Heart Disease 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 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] - 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] - Time-to-first MACE (cardiovascular death, MI, or stroke) was reduced by 28% in all patients and by 37% in patients with inflammation[53] Pediatric Congenital Heart Disease 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][24] - 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][56] - 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] Rexlemestrocel-L for Chronic Low Back Pain (CLBP) 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 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] - 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] - 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] Clinical Trial Results & Regulatory Status 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] - A single injection resulted in significant pain reduction at 12 and 24 months across all 404 subjects in the first Phase 3 trial[67] - 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] Financial Performance Financial Highlights (Half-Year Ended Dec 31, 2023) 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) 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] - Manufacturing expenditure was significantly reduced by 48% to $6.7 million from $12.8 million in the comparative period[27]