Obnitix (MSC-FFM) / Medac - LARVOL DELTA

Treatment of severe acute graft-versus-host disease refractory to multiple lines of therapy: Real-world data from 317 adults treated with the multiple-donor bone marrow-derived mesenchymal stromal cell preparation tomostrocel. (PubMed, Transplant Cell Ther) - "This real-world data analysis showed several efficacy signals and a reassuring safety profile for tomostrocel in multi-refractory aGvHD. Response on Day 28 was predictive for OS, regardless of prior exposure to ruxolitinib. Despite the inherent limitations associated with real-world data collection, these findings suggest that tomostrocel represents a promising treatment option for heavily pretreated and severely ill SR-aGvHD patients. Results of the ongoing randomized controlled trials are eagerly awaited."

Journal • Real-world evidence • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation

BALDER: Trial of Efficacy and Safety of MC0518 Versus Best Available Therapy in Participants With Steroid-Refractory Acute Graft Versus Host Disease (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: medac GmbH | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Pediatrics • Transplantation

REAL-WORLD OUTCOMES OF MESENCHYMAL STROMAL CELL THERAPY IN HEAVILY PRE-TREATED PAEDIATRIC PATIENTS WITH REFRACTORY ACUTE GRAFT-VERSUS-HOST DISEASE (EBMT 2026) - P2 | "Despite limitations of real-world data, MSC-FFM demonstrated good responses with a favourable safety profile in treatment-refractory paediatric aGvHD patients, including those previously exposed to ruxolitinib. Favourable prognostic factors for overall survival are young age, low-grade aGvHD, response at Day 28, and a non-malignant disease. A prospective randomised trial BALDER (NCT06075706) is underway to clarify the efficacy and safety of MSC-FFM in the treatment of steroid-refractory paediatric aGvHD."

Clinical • Real-world • Real-world evidence • Stroma • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease • Pediatrics

REPORT ON THE EFFICACY OF MESENCHYMAL STROMAL CELLS (MSC–OBTINIXTM) IN STEROID AND RUXOLITINIB-REFRACTORY GVHD (SRR-GVHD) WITHIN A COMPASSIONATE USE PROGRAM: AN ITALIAN SINGLE-CENTER EXPERIENCE (EBMT 2026) - "After achieving an only partial response to steroids, ruxolitinib and vedolizumab, he experienced a marked clinical improvement along the course of MSCs infusion, with a progressive resolution of the fecal volume (from 3000 ml/day to about 300 ml/day).The third patient, male, affected by B lymphoblastic leukemia, developed acute cutaneous GvHD on day +15 that evolved to chronic on day +280 post HSCT characterized by lichenoid lesions and diffuse pruritus. The treatment with corticosteroids, ruxolitinib, imatinib, tacrolimus and belumosudil resulted in only limited benefit... Our data show that MSC cell therapy provides a clear improvement in GVHD-related clinical manifestations, both gastrointestinal and cutaneous, and notably without evident adverse events.Based on our observations, MSCs may represent a valuable therapeutic option for patients with therapy-refractory acute and chronic GvHD. In all treated cases, MSCs were associated with meaningful clinical..."

Clinical • Stroma • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Dermatology • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Lymphoblastic Lymphoma • Lymphoma • Myelofibrosis • Pruritus

BALDER: Trial of Efficacy and Safety of MC0518 Versus Best Available Therapy in Participants With Steroid-Refractory Acute Graft Versus Host Disease (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: medac GmbH | Recruiting ➔ Active, not recruiting | Trial primary completion date: Aug 2026 ➔ Mar 2026

Enrollment closed • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Pediatrics • Transplantation

Treatment of steroid-refractory acute graft-versus-host disease by mesenchymal stromal cells: The francophone society of bone marrow transplantation and cellular therapy (SFGM-TC) experience in 43 patients (ASH 2025) - "Forpatients refractory or intolerant to ruxolitinib, there is no standard of care and outcomes are poor, withan ORR to third- and subsequent-line treatment of 36%, median survival of 28 days and OS of 20% at 6months (Abedin BJH 2021).MC0518 (Obnitix) is made from mesenchymal stromal cells (MSCs), which provide a therapeutic effectagainst aGvHD through immunomodulation. Although the mortality of patients with severe and advanced refractory gastrointestinalaGvHD remains high, these results are encouraging with high ORR. These findings require confirmationin randomized trials, preferably on third line to limit immunosuppressive toxicity."

Clinical • Stroma • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Transplantation

Real-World Data Suggest Effectiveness of Allogeneic Mesenchymal Stromal (MSC-FFM) Cells in Ruxolitinib-Refractory Acute Graft-Versus-Host Disease (ASH 2023) - "Safety: Tolerability of MSC-FFM was good, with only five adverse drug reactions reported in three adult patients (chills, BK virus cystitis, increase in C-reactive protein [reported twice in one patient], nausea) and did not result in cessation of MSC treatment or dose reductions. Response: The overall response rate at day +28 was 49% (95%-CI: 41-58%), with 45% (36-55%) in adults and 64% (45-80%) in children. Most responses were durable, resulting in an overall response rate of 49% (41-57%) for both adults and children at 2 months, and 40% (31-48%) at 6 months."

Clinical • Real-world • Real-world evidence • Stroma • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Pediatrics • Transplantation • CRP

MESENCHYMAL STROMAL CELLS AS A SAFE AND EFFECTIVE TREATMENT OPTION FOR HEAVILY PRE-TREATED AGVHD PATIENTS IN A REAL-WORLD SETTING (EBMT 2025) - "The product MSC-FFM is distributed via Hospital Exemption in Germany (under the name Obnitix®) and Named Patient Use in other European countries. This real-world data analyses of 242 adult aGvHD patients who received Obnitix® demonstrate good efficacy and favourable safety of the product. Overall survival correlated with response on Day 28 regardless of prior treatment with ruxolitinib. Despite the inherent limitations associated with real-world data collection, these findings suggest that Obnitix® represents a safe and effective treatment option for heavily pre-treated and severely ill aGvHD patients.​"

Clinical • Real-world • Real-world evidence • Stroma • Acute Graft versus Host Disease • Graft versus Host Disease • Infectious Disease

MESENCHYMAL STROMAL CELLS AS A SAFE AND EFFECTIVE TREATMENT OPTION FOR HEAVILY PRE-TREATED AGVHD PATIENTS IN A REAL-WORLD SETTING (EBMT 2025) - "The product MSC-FFM is distributed via Hospital Exemption in Germany (under the name Obnitix®) and Named Patient Use in other European countries. This real-world data analyses of 242 adult aGvHD patients who received Obnitix® demonstrate good efficacy and favourable safety of the product. Overall survival correlated with response on Day 28 regardless of prior treatment with ruxolitinib. Despite the inherent limitations associated with real-world data collection, these findings suggest that Obnitix® represents a safe and effective treatment option for heavily pre-treated and severely ill aGvHD patients.​"

Clinical • Real-world • Real-world evidence • Stroma • Acute Graft versus Host Disease • Graft versus Host Disease • Infectious Disease

IDUNN: Treatment of Steroid-Refractory Acute Graft-versus-host Disease with Mesenchymal Stromal Cells Versus Best Available Therapy (clinicaltrials.gov) - P3 | N=210 | Recruiting | Sponsor: medac GmbH | Trial completion date: Dec 2027 ➔ Aug 2030 | Trial primary completion date: Dec 2025 ➔ Aug 2027

Stroma • Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation

IDUNN: Treatment Of Steroid-Refractory Acute Graft-versus-host Disease With Mesenchymal Stromal Cells Versus Best Available Therapy (clinicaltrials.gov) - P3 | N=210 | Recruiting | Sponsor: medac GmbH | Trial primary completion date: Jan 2024 ➔ Dec 2025

Stroma • Trial primary completion date • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation

BALDER: Trial of Efficacy and Safety of MC0518 Versus Best Available Therapy in Participants With Steroid-Refractory Acute Graft Versus Host Disease (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: medac GmbH | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Pediatrics • Transplantation

Real-world data suggest effectiveness of the allogeneic mesenchymal stromal cells preparation MSC-FFM in ruxolitinib-refractory acute graft-versus-host disease. (PubMed, J Transl Med) - "A recent real-world analysis of outcomes for 64 adult RR-aGvHD patients not treated with MSCs reports survival of 20%, 16% and 10% beyond 6, 12 and 24 months, respectively (median 28 days). Our data thus suggest effectiveness of MSC-FFM in RR-aGvHD."

Journal • Real-world • Real-world evidence • Stroma • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation

IDUNN: Treatment Of Steroid-Refractory Acute Graft-versus-host Disease With Mesenchymal Stromal Cells Versus Best Available Therapy (clinicaltrials.gov) - P3 | N=210 | Recruiting | Sponsor: medac GmbH | Trial completion date: Dec 2025 ➔ Dec 2027

Stroma • Trial completion date • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation

BALDER: Trial of Efficacy and Safety of MC0518 Versus Best Available Therapy in Participants With Steroid-Refractory Acute Graft Versus Host Disease (clinicaltrials.gov) - P2 | N=48 | Not yet recruiting | Sponsor: medac GmbH

New P2 trial • Stroma • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Pediatrics • Transplantation

SARS-COV-2 FAILS TO INFECT MESENCHYMAL STROMAL CELLS (MSCS) AND DOES NOT ACTIVATE COAGULATION – PRE-CLINICAL INVESTIGATIONS IN SUPPORT OF THERAPEUTIC USE OF MSCS FOR SEVERE COVID-19 (EBMT 2023) - "In summary, because of the lack of SARS-CoV2 surface receptors ACE2 and TMPRSS, Obnitix MSCs cannot be infected with SARS-CoV-2. We consistently observe an inflammatory cellular phenotype and transcriptome which is, however, entirely unaffected by the presence of SARS-CoV-2. These studies support the expectation of safety of Obnitix use in COVID-ARDS."

Preclinical • Stroma • Acute Respiratory Distress Syndrome • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Transplantation • CXCL8 • IFNG • IL12A • IL15

A RANDOMIZED, OPEN LABEL, MULTICENTRE, PHASE 3 TRIAL OF FIRST LINE TREATMENT WITH MSC VERSUS BAT IN PATIENTS WITH STEROID REFRACTORY ACUTE GVHD (IDUNN TRIAL) (EBMT 2022) - P3 | "Prospective data on the efficacy of the MSC product MC0518 for SR-aGVHD are lacking... This randomized prospective trial will provide evidence if the retrospectively collected data demonstrating activity of MSC for SR-aGvHD can be reproduced in a prospective trial setting and if MSC show higher efficacy compared to BAT. A major advantage of MSC could be the limited toxicity profile observed in previous applications of MSC in SR-aGVHD patients. This trial will investigate candidate biomarkers to predict and monitor responses to MSC."

Clinical • P3 data • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Oncology • Transplantation • REG3A • ST2

Sars-Cov-2 Fails to Infect Mesenchymal Stromal Cells (MSCs) - Pre-Clinical Investigations in Support of Therapeutic Use of MSCs for Severe COVID-19 (ASH 2022) - "We consistently observe an inflammatory cellular phenotype and transcriptome which is, however, entirely unaffected by the presence of SARS-CoV-2. These studies support the expectation of safety of Obnitix use in COVID-19 ARDS."

Preclinical • Acute Respiratory Distress Syndrome • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Transplantation • CXCL8 • IFNG • IL12A • IL15 • TMPRSS2

Non-clinical assessment of safety, biodistribution and tumorigenicity of human mesenchymal stromal cells. (PubMed, Toxicol Rep) - "Additionally, we found that the combination of different detection methods (qPCR and ISH) is crucial for a reliable interpretation of biodistribution results. Our data suggest that MC0518 is safe for use in human."

Clinical • Journal • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Oncology • Transplantation

IDUNN: Treatment Of Steroid-Refractory Acute Graft-versus-host Disease With Mesenchymal Stromal Cells Versus Best Available Therapy (clinicaltrials.gov) - P3; N=210; Recruiting; Sponsor: medac GmbH; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Transplantation

IDUNN: Treatment Of Steroid-Refractory Acute Graft-versus-host Disease With Mesenchymal Stromal Cells Versus Best Available Therapy (clinicaltrials.gov) - P3; N=210; Not yet recruiting; Sponsor: medac GmbH; Trial completion date: Sep 2025 ➔ Dec 2025; Initiation date: Mar 2021 ➔ Jun 2021; Trial primary completion date: Sep 2023 ➔ Jan 2024

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Graft versus Host Disease • Immunology • Transplantation

[VIRTUAL] Mesenchymal Stromal Cells (MSCs) Experience in France to Prevent Graft Failure after Hematopoietic Stem Cell Transplantation: A Retrospective Study from the MSCs/CTL Group of the Francophone Society SFGM-TC (ASH 2020) - "Infusion of MSCs at the time of HSCT to prevent graft failure was safe and effective for 6/7 patients. Larger prospective trials are necessary to confirm MSCs impact on engraftment and graft function."

Retrospective data • Acute Lymphocytic Leukemia • Aplastic Anemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD34

IDUNN: Treatment Of Steroid-Refractory Acute Graft-versus-host Disease With Mesenchymal Stromal Cells Versus Best Available Therapy (clinicaltrials.gov) - P3; N=210; Not yet recruiting; Sponsor: medac GmbH

Clinical • New P3 trial • Graft versus Host Disease • Immunology • Transplantation

[VIRTUAL] Mesenchymal Stromal Cell (MSC) Compassionate Use in France in Treatment of Steroid-Refractory Graft-Versus-Host-Disease (GVHD) after Approval By the Expert Committee of Société Française De Greffe De Moelle Et Thérapie Cellulaire (SFGM-TC) (ASH 2020) - "All pts received a ciclosporin-based (CSA) GVHD prophylaxis (CSA alone, n=1; CSA + Mycophenolate Mofetil (MMF) or Methotrexate, n=7)...Five pts were still taking corticosteroids, and six were taking additional immunosuppressive molecules (Tacrolimus, Ruxolitinib, Etanercetp, Inolimomab, MMF) at time of MSC infusion...Besides, we included patient suffering from R-cGVHD. Regarding those results, MSC efficacy and safety should be confirmed in a proper clinical trial."

Graft versus Host Disease • Hematological Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Transplantation

An experimental study in adults and adolescents who underwent stem cell transplantation and developed a sustained acute graft rejection after steroid treatment; to test the safety, tolerability and the effects of treatment with mesenchymal stromal cells MC0518 (clinicaltrialsregister.eu) - P3; N=210; Sponsor: medac Gesellschaft für klinische Spezialpräparate mbH

Clinical • New P3 trial • Graft versus Host Disease • Immunology • Transplantation