Obnitix (MSC-FFM) / Medac - LARVOL DELTA

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 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

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