DISC-3405 Reduces Phlebotomy and Controls Hematocrit in Phase 2 Polycythemia Vera Trial

Disc Medicine reported initial Phase 2 RESTORE-PV (NCT06985147) results showing that investigational anti-TMPRSS6 monoclonal antibody DISC-3405 increased hepcidin, lowered serum iron, and reduced phlebotomy requirements in adults with polycythemia vera (PV). The data, presented at the 2026 Society of Hematologic Oncology (SOHO) annual meeting, also showed stable hematocrit control below 45% through week 26 and an initial improvement in symptom burden.

Targeting Iron Availability in Polycythemia Vera

PV is a chronic myeloproliferative neoplasm characterized by excessive red blood cell production. The resulting increase in blood viscosity raises the risk of thrombotic complications, including myocardial infarction and stroke, while patients may experience fatigue, pruritus, impaired concentration, and splenomegaly.

Phlebotomy remains a central treatment strategy because removing blood also removes iron, limiting further erythropoiesis. DISC-3405 takes a different approach by targeting transmembrane serine protease 6 (TMPRSS6), also known as matriptase-2. Blocking TMPRSS6 increases hepcidin, the key hormone that regulates systemic iron availability, thereby reducing circulating iron and restricting iron supply for red blood cell production.

RESTORE-PV Shows Reduced Need for Phlebotomy

The open-label, multicenter Phase 2 RESTORE-PV trial enrolled 40 adults with PV, with 20 participants assigned to Cohort A and 20 to Cohort B. Following a 4- to 12-week observation period, participants underwent 12 weeks of dose escalation before receiving subcutaneous DISC-3405 at 300 mg every two weeks in Cohort A or every four weeks in Cohort B.

At the data cutoff, all 20 participants in Cohort A had received treatment, with 13 completing 26 weeks. Efficacy data were reported for Cohort A, while baseline and safety data were available from both cohorts.

Among the 13 Cohort A participants completing 26 weeks, mean phlebotomy events fell from 4.0 during the 26 weeks before Day 1 to 0.6 during the 26 weeks after treatment began, a statistically significant reduction (p<0.0001). Eight participants, or 61.5%, remained completely phlebotomy-free during the post-baseline period.

Among nine patients who completed the first maintenance period, 77.8% remained phlebotomy-free during weeks 12 to 32.

Treatment also produced dose-proportional pharmacokinetics, increased hepcidin and ferritin, and reduced serum iron. Mean hematocrit remained stably below 45% through week 26, alongside an initial reduction in symptom burden.

DISC-3405 was generally well tolerated. Reported adverse events were consistent with the underlying disease, while injection-site reactions occurred at a low rate and were mild and self-limited.

Development Plans

Disc Medicine CEO John Quisel said the RESTORE-PV findings suggest that pharmacodynamic effects from iron restriction are translating into clinically relevant hematocrit control, lower phlebotomy use, and symptom improvement.

The company plans to provide an updated RESTORE-PV readout and initial Phase 1b data for DISC-3405 in sickle cell disease by the end of 2026. Disc also presented Phase 2 RALLY-MF data for selcodebart (DISC-0974) in myelofibrosis-associated anemia and expects FDA feedback from an end-of-Phase 2 meeting, along with plans for pivotal development in myelofibrosis, later this year.

DISC-3405 remains investigational and is not approved in any jurisdiction.

Reference

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, Disc Medicine, 09 September 2026