Disc Medicine, Inc. announced data from initial dose cohorts of its ongoing phase 1b/2 study of DISC-0974, a monoclonal antibody designed to suppress hepcidin by inhibiting the hemojuvelin (HJV) co-receptor, in MF patients with anemia. The initial data demonstrated that treatment with DISC-0974 substantially decreased serum hepcidin, increased serum iron and resulted in improvements in hemoglobin or reduced transfusion burden across a broad range of MF patients. The phase 1b/2a multi-center, open-label, ascending-dose study (NCT05320198) is enrolling patients with MF and severe anemia, including both transfusion and non-transfusion dependent patients.

The trial also includes patients who may or may not be receiving concomitant janus kinase (JAK) inhibitor therapy. Study assessments include safety and tolerability of DISC-0974, as well as markers of iron regulation, such as hepcidin and iron, and hematologic parameters. In the phase 1b dose-escalation phase, DISC-0974 is administered subcutaneously every 4 weeks for up to 6 treatments.

Dose escalation is ongoing and the data presented reflect 11 evaluable subjects from the initial three dose levels (14 mg, 28 mg and 50 mg) as of the October 20, 2023 data cutoff. Key initial data presented: DISC-0974 dosing resulted in meaningful, dose-dependent decreases in hepcidin across all treated patients These reductions in hepcidin corresponded to dose-dependent increases in serum iron, Patients dosed with 28 mg of DISC-0974 had a >75% reduction in serum hepcidin and >75% increase in serum iron, Four of seven (57%) evaluable non-transfusion-dependent (NTD) patients at the 28 mg and 50 mg dose levels had a >1.5 g/dL hemoglobin increase from baseline after starting DISC-0974, One of two transfusion-dependent (TD) patients achieved transfusion independence by the Gale Criteria, Hematologic activity was observed in MF patients, regardless of concomitant JAK inhibitor use, To date, DISC-0974 has been generally well-tolerated. The adverse events (AEs) seen in two or more subjects were fatigue, anemia, diarrhea, and nausea.

The majority of AEs were deemed not related to DISC-0974.