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

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

Single Ascending Dose Study of 9MW3011 in Chinese Healthy Subject (clinicaltrials.gov) - P1 | N=48 | Completed | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion

DISC-3405-101: A Study of DISC-3405 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=64 | Completed | Sponsor: Disc Medicine, Inc | Recruiting ➔ Completed

Trial completion

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

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

DISC-3405: Healthy Volunteer Study (GlobeNewswire) - P1 | N=64 | NCT06050915 | Sponsor: Disc Medicine, Inc | "Results showed: 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; Single and repeat dosing of DISC-3405 demonstrated meaningful reductions in hematologic parameters, including reticulocyte hemoglobin, hemoglobin, and hematocrit; 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; These results support Disc’s plans to advance the DISC-3405 program into a Phase 2 study in polycythemia vera in 2025."

New P2 trial • P1 data • Polycythemia Vera

Disc Medicine Reports Third Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "DISC-0974:...The Company expects to initiate a Phase 2 study in anemia of myelofibrosis (MF) by the end of 2024; DISC-3405:...The Company plans to initiate a Phase 2 study in polycythemia vera (PV) in 2025."

New P2 trial • Anemia • Myelofibrosis • Polycythemia Vera

Disc Medicine Secures $200 Million in Non-Dilutive Debt Financing from Hercules Capital, Inc. (GlobeNewswire) - "Disc Medicine, Inc. ..today announced that it has obtained a $200 million non-dilutive term loan facility from Hercules Capital, Inc...This financing provides funding options to support anticipated key catalysts, including...a Phase 2 study of DISC-0974 in anemia of myelofibrosis (MF) and a multiple dose study in anemia of non-dialysis dependent chronic kidney disease (NDD-CKD), and a Phase 2 study of DISC-3405 in polycythemia vera (PV)."

Financing • Anemia • Myelofibrosis • Polycythemia Vera

Disc Medicine Reports Second Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "DISC-0974: Plan for interactions with regulators in the second half of 2024 to determine the optimal Phase 2 study design in anemia of MF; Updated Phase 1b data from DISC-0974 in anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD) is expected to be shared in the second half of 2024; DISC-3405:...Data from the multiple ascending dose (MAD) cohorts of this study expected to be shared in the second half of 2024."

P1 data • Regulatory • Anemia • Chronic Kidney Disease • Hematological Disorders • Hematological Malignancies • Myelofibrosis • Oncology

SINGLE ASCENDING DOSES OF 9MW3011, A MONOCLONAL ANTIBODY TARGETING TMPRSS6, RESULT IN SUSTAINED ELEVATION OF SERUM HEPCIDIN AND REDUCTION OF IRON LEVELS IN HEALTHY VOLUNTEERS (EHA 2024) - "Single intravenous doses of 9MW3011, ranging from 50 to 1800mg, were generallywell-tolerated in healthy volunteers. The treatment elicited evident dose-dependent increases in serumhepcidin levels and led to sustained reductions in both serum iron and TSAT. The observed PD effects, coupledwith favorable safety profile support continued clinical development of 9MW3011."

Clinical • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • KLK7 • TMPRSS6

PHASE 1 HEALTHY VOLUNTEER STUDY OF DISC-3405, A RECOMBINANT HUMANIZED ANTIBODY TARGETING TMPRSS6 (EHA 2024) - "Preliminary findings of single doses of DISC-3405 in healthy volunteers suggest anacceptable safety and tolerability profile, with consistent evidence of target engagement. The study is currentlyongoing, and detailed results across all available dose levels will be presented at the meeting."

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

Disc Medicine Presents Positive Clinical Data Across Portfolio at the European Hematology Association (EHA) 2024 Congress (GlobeNewswire) - P1 | N=64 | NCT06050915 | Sponsor: Disc Medicine, Inc | "Initial data were also presented from the SAD portion of the Phase 1 clinical trial of DISC-3405 in healthy volunteers. In this trial, healthy males and females ages 18 to 65 were given a single dose of placebo (n=10) or DISC-3405 at 75 mg intravenously (IV) (n=6), 37.5 mg subcutaneously (SC) (n=6), 75 mg SC (n=6), 150 mg SC (n=6), or 300 mg SC (n=6). This initial data showed: A meaningful dose-dependent increase in hepcidin and corresponding reduction in serum iron across all dose levels. Mean serum iron reduction in excess of 50% from baseline was achieved in the150- and 300-mg dose groups. Mean serum iron reduction in excess of 50% was sustained for at least 4 weeks for the 300-mg dose group, with meaningful reduction observed in selective hematological parameters (CHr, hemoglobin, and hematocrit)."

P1 data • Hematological Malignancies

Disc Medicine Announces Multiple Presentations Across Portfolio at the European Hematology Association (EHA) 2024 Congress (GlobeNewswire) - "Disc Medicine...announced that it will present data from multiple programs in its hematology portfolio at the upcoming European Hematology Association (EHA) 2024 Congress....Updated data from the ongoing Phase 1b study of DISC-0974 in myelofibrosis (MF) patients with anemia, including a larger data set and longer follow-up, to be shared in a poster; Preliminary data on safety and pharmacodynamic activity from initial single-ascending dose (SAD) cohorts of phase 1 study of DISC-3405 in healthy volunteers."

P1 data • Anemia • Myelofibrosis

Single Ascending Dose Study of 9MW3011 in Chinese Healthy Subject (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Mabwell (Shanghai) Bioscience Co., Ltd.

New P1 trial

FDA Grants Orphan Drug Designation to 9MW3011 (PRNewswire) - "Mabwell (688062.SH), an innovative biopharmaceutical company with entire industry chain, announced that FDA has granted Orphan Drug Designation (ODD) to 9MW3011 (R&D code in the US: MWTX-003/DISC-3405) for the treatment of patients with polycythemia vera (PV)."

Orphan drug • Hematological Malignancies • Oncology • Polycythemia Vera

Disc Medicine Receives FDA Orphan Drug Designation for DISC-3405 for the Treatment of Polycythemia Vera (GlobeNewswire) - "Disc Medicine, Inc...today announced that the United States Food and Drug Administration (FDA) has granted Orphan Drug Designation to DISC-3405 for the treatment of patients with polycythemia vera (PV)....'We look forward to sharing initial data from our ongoing Phase 1 trial of DISC-3405 in healthy volunteers in the first half of 2024.'"

Orphan drug • P1 data • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

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 • Hypertension • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Thrombosis • Transplantation • JAK2 • KLK7 • TMPRSS6