DISC-3405 Reduces Phlebotomy Burden in Polycythemia Vera

Early results from the phase 2 RESTORE-PV trial suggest that the investigational monoclonal antibody DISC-3405 has the potential to reduce the need for phlebotomy and help stabilize hematocrit in patients with polycythemia vera (PV), according to data presented at the Society of Hematologic Oncology (SOHO) Annual Meeting.^1,2

The open-label RESTORE-PV trial includes 40 patients with PV who have been dived evenly between 2 dosing cohorts. The results reported at SOHO are from cohort A, in which patients are receiving DISC-3405 subcutaneously every 2 weeks. Across the escalation and maintenance periods, treatment produced dose-proportional pharmacokinetics (PK) alongside the expected biological effect: hepcidin rose, serum iron fell, and ferritin increased. Hematocrit held below 45% on average out to week 26, a level linked to lower cardiovascular risk in PV, alongside an early signal of symptom improvement.¹

The most clinically meaningful signal came from phlebotomy use. Among the 13 cohort A participants who reached 26 weeks on treatment, phlebotomy procedures averaged 4.0 in the 26 weeks before starting DISC-3405, a figure that dropped to 0.6 over the first 26 weeks on drug (P <.0001). In this group, 61.5% needed no phlebotomy at all from their first dose through week 26, and looking specifically at the trial's first maintenance interval, weeks 12 through 32, 77.8% of the 9 evaluable participants stayed off phlebotomy entirely.¹

DISC-3405 targets transmembrane serine protease 6 (TMPRSS6), a protein that normally suppresses production of the iron-regulating hormone hepcidin. By blocking TMPRSS6, DISC-3405 increases hepcidin levels and restricts iron availability for red blood cell production.¹

“This first look at data from the RESTORE-PV trial shows that the established pharmacodynamics of DISC-3405 are translating well on important clinical measures,” John Quisel, JD, PhD, president and chief executive officer of Disc Medicine, stated in a news release.¹

“Iron restriction is proving to be a transformative treatment approach for a large population of patients with polycythemia vera, with the potential to address their crucial need for hematocrit control while managing symptom burden and reducing reliance on phlebotomy. Our goal for DISC-3405 is to deliver an optimal product presentation combining durable disease control with straightforward, controllable, and convenient dosing using a novel antibody approach. Between this update in PV and our earlier progress in myelofibrosis this year, we have strengthened our commitment to hematologic oncology and now have two programs advancing toward potential pivotal development in myeloproliferative neoplasms,” added Quisel.¹

Safety of DISC-3405

At the data cutoff, all 20 cohort A participants and 18 of 20 cohort B participants had received at least 1 dose of DISC-3405. Reported toxicity tracked closely with what would be expected from PV itself, and the only notable adverse events (AEs) were a small number of injection site reactions, each mild and self-resolving.¹

That profile is consistent with findings from the phase 1 study that first established proof of mechanism for DISC-3405 in healthy volunteers: across single ascending intravenous and subcutaneous doses (37.5 mg to 300 mg) and 2 multiple ascending subcutaneous doses (75 mg and 150 mg every 4 weeks), no participant had a serious AE, a grade 3 or higher AE, or an AE leading to study withdrawal, even as hepcidin rose sharply and serum iron fell by more than 50% in a dose-related pattern.^2,3

RESTORE-PV Trial Design

RESTORE-PV is a multicenter, open-label study enrolling adults with PV. Enrollment begins with a 4- to 12-week observation window, followed by 12 weeks of gradual dose escalation; participants then move to a fixed subcutaneous dose of DISC-3405 (300 mg), given every 2 weeks in cohort A or every 4 weeks in cohort B, for 20 weeks, with the option to continue on that same schedule for up to 20 more weeks.¹

Cohort B's efficacy data were not yet reported at this data cutoff; only baseline and safety data were available for that group. Disc Medicine plans to report an updated RESTORE-PV analysis, by the end of 2026.¹

REFERENCES

1. 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, Inc. Published September 9, 2026. Accessed September 10, 2026. https://tinyurl.com/42akwx8t

2. Liu G, Howell H, Carden MA, Yang H, Savage W. 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. J Clin Pharmacol. 2026;66(5):e70199. doi:10.1002/jcph.70199

3. Liu G, Howell H, Rudin D, Arumugam N, Jadia J, Yang H, Savage W. Phase 1 healthy volunteer study of DISC-3405, a recombinant humanized antibody targeting TMPRSS6 [abstract]. Blood. 2024;144(suppl 1):1092. doi:10.1182/blood-2024-203255