Ryoncil (remestemcel-L-rknd) / Mallinckrodt, Mesoblast, JCR Pharma - LARVOL DELTA

MSB: RYONCIL's $115M launch year revenue fuels late-stage pipeline and strengthens financial position (TradingView)

Sales • Acute Graft versus Host Disease

The future of clinical trials of mesenchymal stromal cells in acute graft-versus-host-disease. (PubMed, Cytotherapy) - "The U.S Food and Drug Administration approval of remestemcel-L for pediatric steroid-refractory acute graft-versus-host disease (GVHD) marks the culmination of 2 decades of efforts to translate mesenchymal stromal cells (MSCs)...Equally important, trial methodologies must explicitly address heterogeneity from MSC manufacturing and patient enrollment. Adaptive/Bayesian designs and master protocols may allow multiple biomarkers and MSC products to be tested simultaneously, with successful combinations being translated into practice, drawing from strategies that have been successful in precision medicine."

Journal • Review • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Pediatrics

Mesoblast Reports Ryoncil Net Revenues of US$36M for the Quarter and US$115M for First Full Year of Product Launch (GlobeNewswire) - "The registration trial for label extension of Ryoncil into adults with SR-aGvHD has commenced and is currently enrolling patients, with up to 40 sites across the U.S. expected to be activated this year representing approximately 60% of the ~8,500 annual U.S. allogeneic adult bone marrow transplant population."

Sales • Trial status • Acute Graft versus Host Disease

Mesoblast Limited reported preliminary net revenue from Ryoncil (remestemcel-L-rknd) of US$36 million for the fourth quarter and US$115 million for the first full year ended June 30, 2026 (StockTitan.net)

Sales • Acute Graft versus Host Disease

Clinical Management of Acute Graft-Versus-Host Disease: An Evidence-Based Review from the ASTCT Committee on Practice Guidelines. (PubMed, Transplant Cell Ther) - "Key recommendations include: 1) The MAGIC grading scheme is supported as the consensus grading scheme for acute GVHD; 2) Clinical tools and non-invasive blood-based biomarkers can aid in risk stratification of patients with newly diagnosed acute GVHD; 3) Corticosteroids remain the recommended first-line systemic therapy for acute GVHD, despite innovative approaches to improve front-line treatment; 4) Ruxolitinib is supported as the second-line therapy standard, while acknowledging remestemcel-L-rknd is a recognized alternative standard for pediatric patients. Ongoing and future studies will seek to improve upon the current treatment paradigm through risk-adapted strategies. Innovative investigative approaches will be needed to address the unmet needs in acute GVHD."

Clinical guideline • Journal • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Pediatrics • Transplantation

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Trial of Remestemcel-L-rknd Added to Ruxolitinib for Grade III-IV Steroid-Refractory Acute Graft-Versus-Host Disease (clinicaltrials.gov) - P3 | N=180 | Not yet recruiting | Sponsor: Mesoblast, Ltd.

New P3 trial • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Acute and Chronic Cutaneous Graft-versus-Host Disease: Diagnosis, Treatment, and Emerging Directions. (PubMed, Am J Clin Dermatol) - "Additionally, we summarize management across the disease continuum, including skin-directed therapy, systemic therapy, and approved therapies for steroid-refractory GVHD such as ruxolitinib and remestemcel-L for acute GVHD and ibrutinib, ruxolitinib, belumosudil, and axatilimab for chronic GVHD. Early dermatologic involvement to diagnose, classify, and participate in multidisciplinary management is critical to improving outcomes for patients experiencing cutaneous GVHD. Biomarker-informed risk stratification and treatment selection, mechanistically informed combination regimens, and steroid-sparing first-line approaches for GVHD treatment are research priorities to enhance efficacy while minimizing toxicity."

Journal • Review • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Transplantation

Mesoblast Reports Ryoncil Net Revenues of US$30.3m and Improved Net Operating Cash Spend for the Quarter to US$4.1 Million (GlobeNewswire)

Sales • Acute Graft versus Host Disease

Study of Mesenchymal Stem Cells for the Treatment of Medically Refractory Crohn's Colitis (clinicaltrials.gov) - P1/2 | N=7 | Terminated | Sponsor: The Cleveland Clinic | N=24 ➔ 7 | Recruiting ➔ Terminated; PI left Cleveland Clinic

Enrollment change • Trial termination • Colon Cancer • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology

Study of Mesenchymal Stem Cells for the Treatment of Medically Refractory Ulcerative Colitis (UC) (clinicaltrials.gov) - P1/2 | N=7 | Terminated | Sponsor: The Cleveland Clinic | N=24 ➔ 7 | Recruiting ➔ Terminated; PI left Cleveland Clinic

Enrollment change • Trial termination • Colon Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Mesoblast (NASDAQ: MESO) Ryoncil sales hit US$30.3M, near US$100M first-year mark (StockTitan.net) - "February and March sales offset weaker, holiday-affected demand in January, and total Ryoncil revenue since launch now approaches US$100 million, helping to strengthen the company’s balance sheet and fund label extension and late-stage programs....The planned R&D Day on April 8, 2026 is positioned to outline the growth strategy for Ryoncil and the broader pipeline. Subsequent disclosures will clarify how recurring Ryoncil revenue, new indications, and partnerships in regions such as Japan, Europe and China translate into sustainable cash flows and commercialization scale."

Pipeline update • Sales • Acute Graft versus Host Disease

Mesoblast Limited…announced that the United States Food and Drug Administration (FDA) has granted Investigational New Drug (IND) clearance to directly proceed for a registrational clinical trial evaluating Ryoncil (remestemcel-L-rknd) in Duchenne muscular dystrophy (DMD) (GlobeNewswire) - "This new registrational trial builds on Ryoncil’s proven safety in children, evidence of efficacy in DMD preclinical models, and FDA-approved manufacturing process....The trial will randomize 76 patients aged 5 to 9 years to either Ryoncil (7 infusions of 2 x 106 cells/kg over 9 months) or placebo, on top of standard of care. The trial’s primary endpoint will be time-to-stand at nine months, a validated FDA endpoint for approval."

IND • Duchenne Muscular Dystrophy

205: Misfit or Missing Piece? Remestemcel-L for Pediatric SR-aGVHD (HOPA 2026) - "This session will review the current data available on efficacy and safety of remestemcel-L and discuss its place in therapy for SR-aGVHD. UAN: 0465-0000-26-039-L01-P Knowledge or Application Based: Knowledge Learning Objectives: Summarize study data that led to the FDA approval of remestemcel-L for pediatric steroid refractory acute graft versus host diseaseDiscuss place in therapy for remestemcel-L in relation to other therapies for graft versus host disease and the impact cost of treatment may have on use"

Clinical • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Pediatrics

Breast cancer stem cells induce IRF6 in stromal fibroblasts to upregulate stromagenesis (DKK 2026) - "Based on our findings, we propose that fibroblast IRF6 function is an important factor in the development of the stromal microenvironment and in sustaining the BCSC tumor niche1. Indication of source (Optional, please delete this paragraph if you do not have an indication of source):1 Muralidharan H, Hansen T, Steinle A, Schumacher D, Stickeler E, Maurer J. Breast Cancer Stem Cells Upregulate IRF6 in Stromal Fibroblasts to Induce Stromagenesis. Cells."

Cancer stem • Stroma • Breast Cancer • Fibrosis • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • CAFs • IRF6

Ryoncil Profits Underpinning Substantial Growth Pipeline (The Manila Times) - "Total revenue of US$51.3 million (A$78.3 million),2 up from US$3.2 million; Successful U.S. commercial launch of Ryoncil (remestemcel-L-rknd) generated gross sales of US$57.0 million and revenue of US$48.7 million after gross to net adjustment; Ryoncil gross profit, excluding amortization, was US$44.2 million versus nil in the prior year period. Direct selling costs were US$7.7 million...To date 49 transplant centers have been onboarded, with a target of 64 centers which account for 94% of transplants performed in the U.S. Ryoncil."

Commercial • Sales • Acute Graft versus Host Disease

Mesoblast anticipates full-year fiscal 2026 Ryoncil net revenue to range between US$110 million and US$120 million. (The Manila Times)

Sales projection • Acute Graft versus Host Disease

OPERATIONAL HIGHLIGHTS FOR H1 FY2026 (The Manila Times) - "Mesoblast intends to expand the clinical indications of Ryoncil for life-cycle extension in both adults and children with life-threatening inflammatory conditions. The final protocol design for the Phase 3 trial of Ryoncil as part of the second-line treatment regimen in adults with steroid-refractory acute graft versus host disease (SR-aGvHD), a population approximately three times the size of the pediatric SR-aGvHD population, is locked down following a recent meeting with FDA and will be provided to the Institutional Review Board (IRB) in March for site initiation."

New P3 trial • Acute Graft versus Host Disease

High Survival Rates With Ryoncil in EIND Program Emphasize Importance of Earlier Use in Both Children and Adults With SR-aGvHD (GlobeNewswire) - "...Data presented at the February 2026 Tandem Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for Blood and Marrow Transplant Research (CIBMTR)....The study results showed that Ryoncil (remestemcel-L-rknd) achieved similarly high survival outcomes in steroid-refractory acute graft-versus-host disease (SR-aGvHD) irrespective whether used in children or adults, as second or third line, and in ruxolitinib naive or resistant patients....Importantly, of the 53 patients with SR-aGvHD who received Ryoncil as ≥ third line treatment under the Emergency Investigational New Drug (EIND) program (89% grade III/IV disease), 15% died before being able to complete a full treatment course of Ryoncil..."

Clinical data • Acute Graft versus Host Disease

Exploring new directions: Remestemcel-L-rknd added to ruxolitinib as initial treatment for steroid refractory acute GVHD (CTN2303): A phase III placebo-controlled study developed by Mesoblast and the BMT Clinical Trials Network. (TCT-ASTCT-CIBMTR 2026) - No abstract available

Clinical • P3 data • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Remestemcel-L-Rknd (Ryoncil) Improves Survival after Failure of Second-Line Treatment for SR-aGVHD (TCT-ASTCT-CIBMTR 2026) - P3 | "Amongst heavily pretreated patients with third line or greater SR-GVHD, 89 % with grades III/IV disease, remestemcel-L-rknd had significant activity with overall day 100 OS of 68%, and similar survival outcomes across both pediatric and adult age groups. This was significantly higher than has been reported with other treatments used in third-line patients and very similar to OS seen with remestemcel- L-rknd in second line children with SR-aGVHD (Figure 1B). Given the high early mortality risk of SR-aGVHD after failure of second line agents, these results highlight that earlier use of remestemcel-L-rknd may increase OS."

Clinical • Acute Graft versus Host Disease • Graft versus Host Disease

Operational Highlights for Quarter Ended December 31, 2025 (GlobeNewswire) - "Given the continued unmet need in adults with severe SR-aGvHD, a pivotal trial of Ryoncil is expected to commence site enrollment this quarter for label extension of Ryoncil for use in adults..."

New trial • Acute Graft versus Host Disease

Real-World Commercial Experience with Ryoncil Shows 84% Survival of Children with SR-aGvHD After Completing 28-Days of Treatment (GlobeNewswire) - "Of the first 25 patients treated with Ryoncil in a ‘real-world’ clinical setting post launch, 21 were alive (84%) and completed the initial 28-day treatment regimen as per the FDA approval label. The four patients who did not complete the 28-day treatment course had been offered and failed other therapies prior to use of Ryoncil and died of severe SR-aGvHD within 28 days. These early data are consistent with the prior clinical experience with Ryoncil....A pivotal trial of Ryoncil in adults with severe SR-aGvHD will be conducted with the NIH-funded Bone Marrow Transplant Clinical Trials Network (BMT-CTN) and is expected to commence site enrollment this quarter."

New trial • Real-world • Acute Graft versus Host Disease

Ryoncil Net Revenues Increase for the Quarter to US$30M (GlobeNewswire) - "Ryoncil gross sales for the quarter were US$35 million, a 60% increase on the prior quarter ended September 30, 2025, and net revenues were US$30 million."

Sales • Acute Graft versus Host Disease

Mesoblast rises as Ryoncil sales climb 60% in December quarter (MSN News) - "Mesoblast...ADRs added ~6% on Friday after the Australian biotech said that gross revenue from its cell therapy Ryoncil reached $35.1M during the December 2025 quarter, indicating a ~60% jump from the preceding quarter....In a regulatory filing on Friday, Mesoblast (MESO) disclosed that Ryoncil would undergo a pivotal trial as part of a second-line regimen for adults with SR-aGVHD, a market nearly three times larger than the pediatric population."

New trial • Sales • Acute Graft versus Host Disease

Comparative efficacy and safety of ruxolitinib and remestemcel-l in the treatment of steroid-refractory acute graft-versus-host disease: Systematic review and meta-analysis (ASH 2025) - "Both Ruxolitinib and Remestemcel-L demonstrate significant efficacy in treating steroid-refractory acute graft-versus-host disease, with Remestemcel-L showing superior outcomes in completeand overall remission. Both therapies exhibit favorable safety profiles, though clinical decisions shouldconsider the differences in adverse events. Risk of Bias was moderate in the analyzed studies."

Retrospective data • Review • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology