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

Restore-PV: A Phase 2 Open-Label Study Evaluating the Safety and Efficacy of the Anti-TMPRSS6 Monoclonal Antibody DISC-3405 in Participants with Polycythemia Vera (SOHO 2026) - P2 | "Participants on CRT (hydroxyurea, interferon, ruxolitinib) must be on a stable dose. DISC-3405 is the first anti-TMPRSS6 mAb tested to reduce PHL burden in PV. Additional baseline and observation data will be presented."

Clinical • P2 data • Oncology • Polycythemia Vera • JAK2 • KLK7 • ST14 • TMPRSS6

Disc plans to provide…initial data from the Phase 1b trial of DISC-3405 in sickle cell disease, by the end of 2026 (GlobeNewswire)

P1 data • Sickle Cell Disease

Disc Medicine Presents Initial Results from RESTORE-PV Phase 2 Trial in Patients with Polycythemia Vera (PV) at the 14th Society of Hematologic Oncology (SOHO) Annual Meeting (GlobeNewswire) - "The Phase 2 multi-center, open-label RESTORE-PV trial enrolled 40 adult participants with PV, including 20 participants in Cohort A and 20 participants in Cohort B....Across escalation and maintenance periods, results demonstrated: (i) Dose-proportional PK, elevation of hepcidin, reduction of serum iron, and increase in ferritin (Cohort A); (ii) Control of hematocrit, with mean hematocrit maintained stably <45% through week 26 which led to initial improvement in symptom burden (Cohort A); (iii) DISC-3405 significantly reduced phlebotomy events in Cohort A participants. For n=13 patients completing 26 weeks of study: Mean total phlebotomy events significantly decreased from 4.0 in 26 weeks at baseline to 0.6 in 26 weeks post-Day 1 (p<0.0001)....Disc plans to provide an update on RESTORE-PV...by the end of 2026."

P2 data • Polycythemia Vera

Disc Medicine…announced that it will present data from multiple clinical programs, including an oral presentation of initial data from the RESTORE-PV trial of DISC-3405 in patients with polycythemia vera (PV), at the SOHO Annual Meeting (GlobeNewswire) - "The oral presentation of data from the Phase 2 RESTORE-PV study in patients with polycythemia vera will share baseline and safety data for N=40 patients from Cohorts A and B, as well as PK, PD, and other efficacy endpoints for the N=20 patients from Cohort A."

P2 data • Polycythemia Vera

RESTORE-PV: A Phase 2, Open-Label Study of DISC-3405 in Participants With Polycythemia Vera (PV) (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Disc Medicine, Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Polycythemia Vera

Recent Highlights and Anticipated Milestones: DISC-3405 (Disc Medicine Press Release) - "Completed enrollment for RESTORE-PV Phase 2 study in patients with polycythemia vera with initial data expected in Q3 2026; Progressing Phase 1b study in patients with sickle cell disease with initial data expected in Q4 2026."

Enrollment closed • P1 data • P2 data • Polycythemia Vera • Sickle Cell Disease

RESTORE-PV – A PHASE 2 OPEN-LABEL STUDY EVALUATING THE SAFETY AND EFFICACY OF THE ANTI-TMPRSS6 MONOCLONAL ANTIBODY DISC-3405 IN PARTICIPANTS WITH POLYCYTHEMIA VERA (EHA 2026) - P2 | "Participants receiving CRT (ie, hydroxyurea [HU], interferon, ruxolitinib) must have been on the therapy for at least 6 months and on a stable PV treatment regimen for at least 2 months. Summary/Conclusion DISC-3405 is the first anti-TMPRSS6 mAb tested to reduce PHL burden in patients with PV. Additional baseline and observation period details will be presented ."

Clinical • P2 data • Cardiovascular • Hematological Disorders • Myeloproliferative Neoplasm • Polycythemia Vera • Thrombosis • KLK7 • ST14 • TMPRSS6

A PHASE IB STUDY OF 9MW3011, A FIRST-IN-CLASS ANTI-TMPRSS6 ANTIBODY, IN RELAPSED/REFRACTORY PATIENTS WITH POLYCYTHEMIA VERA (EHA 2026) - P1 | "CTF is considered as the absence of cytoreductive intervention such as hydroxyurea and interferon- α. Above all support further clinical investigations. Corresponding Author: Zhijian Xiao, [email protected] Favorable Safety, Tolerability, and Preliminary Efficacy of 9MW3011"

Clinical • P1 data • Chronic Eosinophilic Leukemia • Hematological Disorders • Hematological Malignancies • Myeloproliferative Neoplasm • Polycythemia Vera • KLK7 • TMPRSS6

DISC-3405: RESTORE-PV Trial-in-Progress poster (GlobeNewswire) - "Disc Medicine presents positive clinical updates at the 2026 European Hematology Association (EHA) Annual Meeting....RESTORE-PV is a Phase 2 open-label study of the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of DISC-3405 in patients with polycythemia vera. Initial data from the trial is expected in Q4 2026."

P2 data • Trial status • Polycythemia Vera

Disc Medicine Announces Multiple Presentations Across Portfolio at the European Hematology Association (EHA) 2026 Congress (Disc Medicine Press Release) - "Additional abstracts highlighting updates on...DISC-3405 trial in progress for polycythemia vera"

Trial status • Polycythemia Vera

Disc Medicine Reports First Quarter 2026 Financial Results and Provides Business Update (GlobeNewswire) - "Progressing ongoing Phase 2 study of DISC-3405 in polycythemia vera (PV) and Phase 1b study of DISC-3405 in sickle cell disease (SCD), with data from both studies expected in Q4 2026."

P1 data • Polycythemia Vera • Sickle Cell Disease

A Phase 1 Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study of DISC-3405, a Novel Recombinant Humanized Monoclonal Antibody Targeting TMPRSS6, in Adult Healthy Volunteers. (PubMed, J Clin Pharmacol) - "Single and repeated dosing of DISC-3405 produced reductions in reticulocyte hemoglobin, hemoglobin, and hematocrit. Overall, DISC-3405 was well tolerated with PK/PD data supporting further development for patients who could benefit from iron restriction, such as those with polycythemia vera."

Clinical • Journal • P1 data • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • KLK7 • SMAD4 • TMPRSS6

Recent Highlights and Anticipated Milestones: DISC-3405: Anti-TMPRSS6 Antibody (Hepcidin Induction) (GlobeNewswire) - "Progressing ongoing Phase 2 study in patients with polycythemia vera with initial data expected in 2H 2026; Initiated Phase 1b study in sickle cell disease in Q4 2025 with initial data expected in 2H 2026."

P1 data • P2 data • Polycythemia Vera • Sickle Cell Disease

Key Business Objectives and Milestones for 2026:…DISC-3405: Anti-TMPRSS6 Antibody (Hepcidin Induction) (GlobeNewswire) - "(i) Progress ongoing Phase 2 PV trial with updated data expected H2 2026; (ii) Progress ongoing Phase 1b SCD trial with updated data expected H2 2026."

Clinical data • Trial status • Polycythemia Vera • Sickle Cell Disease

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