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

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

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) - No abstract available

Cancer stem • Stroma • Breast Cancer • Oncology • Solid Tumor • IRF6

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

Independent Study Presented at American Society of Hematology (ASH) Annual Meeting Concludes Remestemcel-L Superior to Ruxolitinib in Clinical Outcomes as Treatment for SR-aGvHD (GlobeNewswire) - "The meta-analysis involved 2,732 patients (1,993 in the treatment arms and 523 in the control arms) across 11 studies. Among treatment groups, 644 patients received remestemcel-L and 1,349 received ruxolitinib. While both ruxolitinib and remestemcel-L significantly improved quality of life in treating SR-aGvHD, remestemcel-L showed superior outcomes in complete and overall remission as well as differences in hematology, cardiac and hepatic adverse events. The authors also concluded that while both therapies exhibit favorable safety profiles, clinical decisions should consider the differences in adverse events."

Review • Acute Graft versus Host Disease

Mesoblast Trading Update at Annual General Meeting Highlights Continued Strong Growth in Ryoncil Revenue (GlobeNewswire) - "For the quarter ending December 31, 2025, management expects gross revenue of more than US$30.0 million from sales of Ryoncil (remestemcel-L-rknd). This represents more than 37% increase on the US$21.9 million in gross revenue from Ryoncil in the prior quarter ended September 30, 2025."

Sales projection • Acute Graft versus Host Disease

Mesoblast and BMT CTN to Initiate Pivotal Trial of Ryoncil as Part of First-Line Regimen in Adults with Severe Acute GVHD Refractory to Steroids (GlobeNewswire) - "Mesoblast recently met with FDA to discuss the most appropriate patient population and timing of treatment in a pivotal trial of Ryoncil for adults with severe SR-aGvHD. In order to give adult patients with severe SR-aGvHD the best chance of survival, patients will be randomized in the trial as early as possible after corticosteroid refractoriness to receive ruxolitinib alone or combined with Ryoncil. The trial protocol will be provided to FDA in order to initiate enrollment in the first quarter of 2026."

Commercial • New P3 trial • Acute Graft versus Host Disease

Efficacy of Treatment Options for Children with Steroid-Refractory Acute Gvhd (ASH 2023) - "Only a few small size clinical trials were conducted for children with SR-aGVHD which poses a unique challenge for FDA to approve new therapies for SR-aGVHD. Despite a small number (n=9: 5 ruxolitinib arm and 4 control arm) of children (12-18 years) enrolled in REACH II study, ruxolitinib was FDA approved for children>12 years of age. Long-term efficacy outcomes of children enrolled in clinical trials were reported only for remestemcel-L and showed that approximately half survived beyond 3 years."

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

Ryoncil Revenues Increase 66% in Second Quarter Post Launch (GlobeNewswire) - "Mesoblast Limited...announced gross revenue of US$21.9 million on Ryoncil (remestemcel-L-rknd) sales for the quarter ended September 30, 2025....Ryoncil is...the only product approved for children under age 12 with steroid-refractory acute graft-versus-host disease (SR-aGvHD)."

Sales • Acute Graft versus Host Disease

Mesoblast Limited…announced that a specific Healthcare Common Procedure Coding System (HCPCS) J-Code assigned to Ryoncil (remestemcel-L-rknd) by United States Medicare & Medicaid Services (CMS) became active for billing and reimbursement on October 1, 2025 (GlobeNewswire) - "The new permanent J-Code, J3402, provides a standardized, clear, permanent, and specific billing pathway for Ryoncil by Medicaid....Ryoncil is...the only product approved for children under age 12 with steroid-refractory acute graft-versus-host disease (SR-aGvHD)."

Reimbursement • Acute Graft versus Host Disease

Remestemcel-L-rknd (Ryoncil): the first approved cellular therapy for steroid-refractory acute GVHD. (PubMed, Blood) - "Until recently, the JAK1/2 inhibitor, ruxolitinib (Jakafi), was the only therapy for steroid-refractory acute graft-versus-host disease (SR-aGVHD) approved by the U.S. Food and Drug Administration (FDA) for use in patients older than 12 years. Now the FDA has approved a potent mesenchymal stromal cell product (MSC), remestemcel-L-rknd (Ryoncil), for children 18 and younger, showing 70% response rates and nearly 70% six-month survival. In this Spotlight, we highlight this important advance in the field."

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

Stromagenesis and cancer-associated fibroblast heterogeneity in primary tumors and metastasis: focus in non-small cell lung cancer. (PubMed, FEBS Open Bio) - "We also highlight the critical role of smoking through epigenetic reprogramming of the TGF-β/SMAD3 pathway. These advances are beginning to delineate how CAF heterogeneity depends on the stage and histologic subtype in NSCLC."

Heterogeneity • Journal • Review • Fibrosis • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • CAFs • SMAD3 • TGFB1

JAK2 Inhibitors and Emerging Therapies in Graft-Versus-Host Disease: Current Perspectives and Future Directions. (PubMed, Biomedicines) - "The introduction of ruxolitinib, a selective JAK1/2 inhibitor, has transformed the treatment landscape for steroid-refractory acute and chronic GVHD, leading to improved response rates and durable symptom control...In 2024, the FDA approved axatilimab, a CSF-1R inhibitor that targets monocyte-derived macrophages in fibrotic chronic GVHD, and remestemcel-L, an allogeneic mesenchymal stromal cell therapy, for pediatric steroid-refractory acute GVHD...The integration of these tools with organ-specific and personalized approaches marks a shift toward more precise, durable, and tolerable GVHD therapy. This review highlights the current state and future direction of JAK2 inhibition and complementary therapies in the evolving GVHD treatment paradigm."

Journal • Review • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Pediatrics • Transplantation • IFNG • IL6

Successful Commercial Launch of Ryoncil (GlobeNewswire) - "Mesoblast Limited...announced gross revenue from sales of Ryoncil (remestemcel-L-rknd) through the first quarter post product launch. Ryoncil is the first and only FDA approved mesenchymal stromal cell (MSC) product in the Unites States and became commercially available for purchase on March 28, 2025, within one quarter of receiving FDA approval for treatment of steroid-refractory acute graft-versus-host disease (SR-aGvHD) in children....FINANCIAL HIGHLIGHTS FOR QUARTER ENDED JUNE 30, 2025: (i) US$13.2 million gross revenue (unaudited) from sales of Ryoncil post-launch March 28 through to June 30.1; (ii) US$1.6 million revenue from royalties on sales of TEMCELL HS Inj.2 sold in Japan by our licensee."

Sales • Acute Graft versus Host Disease

Mesoblast Maintains Momentum With FDA on…Label Extension for Ryoncil in Adults With GvHD (GlobeNewswire) - "Mesoblast...provided an update on continued momentum with United States Food and Drug Administration (FDA) regarding...label extension for Ryoncil (remestemcel-L-rknd) in adults with steroid refractory acute graft versus host disease (SR-aGvHD)....In early July, Mesoblast has an upcoming meeting with FDA to discuss a pivotal trial of Ryoncil in adults with SR-aGvHD. This trial will be conducted with the NIH-funded Bone Marrow Transplant Clinical Trials Network (BMT-CTN), the objective being to extend the product’s label from children to adults with SR-aGvHD."

FDA event • Acute Graft versus Host Disease

Single-Cell RNA Sequencing and Inferred Protein Activity Analysis Reveal a Distinct Tumor Phenotype in Early-Onset Colorectal Cancer Patients. (PubMed, bioRxiv) - "Notably, we define a previously unrecognized epithelial subpopulation in EO-CRC, marked by high expression of toll-like receptor 4 (TLR4) and C-C chemokine receptor type 5 (CCR5)-key mediators of inflammation-driven tumor progression and fibroblast recruitment. These findings suggest that EO-CRC may be driven by a tumor-intrinsic inflammatory phenotype with enhanced stromagenesis, providing new insights into potential mechanisms underlying its increasing incidence in young adults."

IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • TLR4

Remestemcel-L-rknd for Steroid-Refractory Acute Graft-vs-Host Disease in Pediatric Patients. (PubMed, JAMA) - No abstract available

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

FDA Provides Seven Years of Orphan-Drug Exclusive Approval for Ryoncil (GlobeNewswire) - "Mesoblast...announced that it has received seven years of orphan-drug exclusive approval from U.S. Food and Drug Administration (FDA) for Ryoncil (remestemcel-L) for treatment of steroid-refractory acute graft versus host disease (SR-aGvHD) in pediatric patients 2 months of age and older...Separately, Mesoblast has biologic exclusivity preventing another sponsor from referencing the Ryoncil biologic license application (BLA) until December 2036, twelve years from its first approval which would prevent market entry by a biosimilar...These statutory exclusivities are in addition to Mesoblast’s strong U.S. intellectual property position on MSC composition of matter, manufacturing and indications, including SR-aGvHD, that provide a commercial barrier to entry against competitors through 2044."

Commercial • Orphan drug • Acute Graft versus Host Disease

Combined treatment with mesenchymal stem cells and therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy: a phase 1/2 randomized trial. (PubMed, Sci Rep) - "No marked differences in safety profile were observed between the groups. These results indicate that the efficacy of Temcell combined with hypothermia is comparable to therapeutic hypothermia for patients with nHIE.Clinical Trial Registration: jRCT1080224818."

Clinical • Journal • P1/2 data • Acute Graft versus Host Disease • CNS Disorders • Graft versus Host Disease • Immunology