DISC-3405 / Mabwell (Shanghai) Biosci, Disc Medicine - LARVOL DELTA

A phase 2, open-label study of the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of DISC-3405 in participants with polycythemia vera (PV) (ASH 2025) - P2 | "Participants receiving CRT must have been on the therapy for at least 6 months andon a stable PV treatment regimen, including hydroxyurea, interferon, or ruxolitinib, for at least 2 months.Participants treated with only PHL must have stopped CRT 6 months before screening. The study will enroll participants from approximately 15-20 sites in the United States. Additional detailscan be found at https://clinicaltrials.gov/study/NCT06985147."

Clinical • P2 data • PK/PD data • Cervical Cancer • Genito-urinary Cancer • Myeloproliferative Neoplasm • Polycythemia Vera • Prostate Cancer • Solid Tumor • Thrombosis • JAK2 • KLK7 • ST14 • TMPRSS6

Disc also shared a poster overviewing the trial design for the ongoing Phase 2 study of the anti-TMPRSS6 antibody DISC-3405 in polycythemia vera requiring frequent phlebotomy. (GlobeNewswire)

Clinical protocol • Polycythemia Vera

A Phase 1b, Open-Label Study of DISC-3405 in Participants With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Disc Medicine, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Phase 2, Open-Label Study of DISC-3405 in Participants With Polycythemia Vera (PV) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Disc Medicine, Inc | N=20 ➔ 60

Enrollment change • Polycythemia Vera

An Iron Pulse Study to Assess Oral Iron Absorption Following Treatment With DISC-3405 in Healthy Volunteers (MPN 2025) - No abstract available

Clinical

Single- and Multiple-Ascending Doses of DISC-3405, a Recombinant Humanized Antibody Targeting TMPRSS6, Increased Hepcidin and Reduced Iron and Hematocrit in Healthy Volunteers (MPN 2025) - No abstract available

Clinical • TMPRSS6

Novel Anti-TMPRSS6 Monoclonal Antibody Provides a Potential Therapeutic Approach for the Treatment of Polycythemia Vera (ASH 2023) - "Taken together, the anti-TMPRSS6 antibody offers a promising therapeutic approach in the management of PV, where erythrocytosis and high HCT levels are associated with poor outcomes. A Phase I clinical trial with MWTx-003 in healthy volunteers has been initiated in China."

Beta-Thalassemia • Bone Marrow Transplantation • Cardiovascular • Genetic Disorders • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Thrombosis • Transplantation • JAK2 • KLK7 • TMPRSS6

Initiated Phase 1b study of DISC-3405 in patients with SCD in October 2025 with initial data expected in 2026 (GlobeNewswire)

P1 data • Sickle Cell Disease

Progressing ongoing Phase 2 study of DISC-3405 in patients with PV with initial data expected in 2026 (GlobeNewswire)

P2 data • Polycythemia Vera

Pharmacological Inhibition of TMPRSS6 Decreases Hemoglobin Concentration and Red Blood Cell (RBC) Hemolysis in a Mouse Model of Sickle Cell Disease (ASH 2024) - P1 | "DISC-3405 is a humanized monoclonal antibody blocking the biological action of TMPRSS6 with subsequent upregulation of hepcidin, leading to decreased iron absorption by enterocytes and decreased iron release from stores...r4K12B treatment at 10 mg/kg significantly reduced the spleen index compared to the vehicle group, indicating decreased extramedullary erythropoiesis. Taken together, these results suggest that iron restriction, through inhibition of TMPRSS6, may provide therapeutic benefits to SCD patients by reducing HbS concentration within the RBCs."

Preclinical • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Inflammation • Polycythemia Vera • Sickle Cell Disease • KLK7 • TMPRSS6

Disc Medicine Announces Presentation of Initial Data from RALLY-MF Phase 2 Trial in Patients with Myelofibrosis (MF) and Anemia at the 67th American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "We will also present a poster on the design of our ongoing Phase 2 trial of DISC-3405 in polycythemia vera. We expect to share an initial readout for this trial, as well as for the Phase 1b trial of DISC-3405 in sickle cell disease, in 2026."

Clinical data • Clinical protocol • Anemia • Myelofibrosis • Polycythemia Vera • Sickle Cell Disease

Phase 1 Healthy Volunteer Study of DISC-3405, a Recombinant Humanized Antibody Targeting TMPRSS6 (ASH 2024) - "Conclusion : Preliminary findings of both SAD and MAD cohorts of DISC-3405 in healthy volunteers suggest an acceptable safety and tolerability profile, with consistent evidence of target engagement. The dosing phase of this study was completed, and detailed results across all cohorts will be presented."

Clinical • P1 data • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Hepatology • Polycythemia Vera • KLK7 • ST14 • TMPRSS6

A Phase 1b, Open-Label Study of DISC-3405 in Participants With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Disc Medicine, Inc

New P1 trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Single- and Multiple-Ascending Doses of DISC-3405, a Recombinant Humanized Antibody Targeting TMPRSS6, Increased Hepcidin and Reduced Iron and Hematocrit in Healthy Volunteers (SOHO 2025) - "DISC-3405 was well tolerated, and proof of concept of the mechanism of action was demonstrated in HVs. The favorable safety, tolerability, and PK/PD profiles support the use of DISC-3405 in patient populations at risk of iron overload. Detailed results across all HV cohorts will be reviewed."

Clinical • Oncology • Polycythemia Vera • ST14 • TMPRSS6

A Phase 2, Open-Label Study of DISC-3405 in Participants With Polycythemia Vera (PV) (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Disc Medicine, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Polycythemia Vera

Recent Highlights and Anticipated Milestones: (GlobeNewswire) - "Progressing RALLY-MF Phase 2 study of DISC-0974 in patients with anemia of MF with initial data expected in Q4 2025: Exploratory cohort for patients on concomitant momelotinib or pacritinib fully enrolled, and trial protocol updated to allow patients on these therapies into the main study cohorts....Initiated a Phase 2 study of DISC-3405 in patients with PV with initial data expected in 2026."

P2 data • Trial status • Anemia • Myelofibrosis • Polycythemia Vera

SINGLE- AND MULTIPLE-ASCENDING DOSES OF DISC-3405, A RECOMBINANT HUMANIZED ANTIBODY TARGETING TMPRSS6, INCREASED HEPCIDIN AND REDUCED IRON AND HEMATOCRIT IN HEALTHY VOLUNTEERS (EHA 2025) - "DISC-3405 was well tolerated, and proof of concept of the mechanism of action was demonstrated in human HVs. The favorable safety, tolerability, and PK/PD profiles support the use of DISC-3405 in patient populations at risk of iron overload. Detailed results across all HV cohorts will be reviewed."

Clinical • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Hepatology • Polycythemia Vera • KLK7 • ST14 • TMPRSS6

AN IRON PULSE STUDY TO ASSESS ORAL IRON ABSORPTION FOLLOWING TREATMENT WITH DISC-3405 IN HEALTHY VOLUNTEERS (EHA 2025) - "Preliminary results from this oral iron pulse study suggest that DISC-3405 efficiently blocks iron absorption in the gut by inducing hepcidin production."

Clinical • KLK7 • ST14 • TMPRSS6

Phase 1 Healthy Volunteer Study (GlobeNewswire) - P1 | N=64 | NCT06050915 | Sponsor: Disc Medicine, Inc | "Updated SAD/MAD data from the Phase 1 trial of DISC-3405 in healthy volunteers were presented...DISC-3405 produced dose-related increases in serum hepcidin with corresponding reductions in serum iron across all dose levels; DISC-3405 resulted in deep reductions in serum iron (ranging from 50-80% from baseline) that were sustained and support a once-monthly SC dosing regimen; DISC-3405 was generally well-tolerated at all evaluated dose levels, with no serious adverse events (AEs), greater than Grade 2 AEs, or AEs leading to study withdrawal...Disc has now initiated a Phase 2 trial of DISC-3405 in PV with initial results expected in 2026."

P1 data • P2 data • Polycythemia Vera

Disc Medicine Announces Multiple Presentations Across Portfolio at the European Hematology Association (EHA) 2025 Congress (GlobeNewswire) - "Poster presentations across all programs, including data from HELIOS long-term extension trial of bitopertin in erythropoietic protoporphyria (EPP), additional durability data from Phase 1b study of DISC-0974 in anemia of myelofibrosis (MF), and additional data from DISC-3405 studies in healthy volunteers."

Clinical data • Anemia • Hematological Disorders • Myelofibrosis

A Phase 2, Open-Label Study of DISC-3405 in Participants With Polycythemia Vera (PV) (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Disc Medicine, Inc

New P2 trial • Polycythemia Vera

Disc Medicine Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "Plan to initiate Phase 2 study of DISC-3405 in polycythemia vera (PV) in H1 2025; Expect data readouts for DISC-0974 program in H2 2025, including initial results of Phase 2 anemia of myelofibrosis (MF) study."

New P2 trial • P2 data • Anemia • Myelofibrosis • Polycythemia Vera

Disc Medicine Highlights Recent Achievements Across Hematology Portfolio and Key Business Objectives and Milestones for 2025 (GlobeNewswire) - "Initial data from an ongoing phase 2 study of DISC-0974 (anti-hemojuvelin antibody) in anemia of myelofibrosis (MF) expected H2 2025....Initiation of phase 2 study of DISC-3405 (anti-TMPRSS6 antibody) in polycythemia vera (PV) planned for H1 2025."

New P2 trial • P2 data • Myelofibrosis • Polycythemia Vera

A Multiple Ascending Dose Study of 9MW3011 in Patients With Non-transfusion-dependent β-thalassemia (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

New P1 trial • Beta-Thalassemia • Genetic Disorders

A Study of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of 9MW3011 in Patients With Polycythemia Vera (clinicaltrials.gov) - P1 | N=108 | Recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

New P1 trial • Polycythemia Vera