Disc Medicine's DISC-3405 heads to Q4 2026 PV data with no rival in human testing
The Phase 2 trial's primary endpoints are safety and tolerability, not a phlebotomy-response bar, and no other TMPRSS6 antibody has reached the clinic in polycythemia vera.
Executive Summary
- Disc Medicine is heading toward its first human polycythemia vera data for an anti-TMPRSS6 antibody, a mechanism no other company has advanced past early testing in this disease.
- The registered primary endpoints test tolerability and safety, not the phlebotomy-response measure that will likely draw the most attention; that response measure sits among the secondary endpoints.
- The trial's enrollment target rose once early in the program and has held steady since, and the study has moved cleanly from not-yet-recruiting to recruiting without the churn that would raise execution concerns.
- No other antibody or same-target program has reached Phase 2 in this indication, leaving the readout without a direct precedent to benchmark against.
The catalyst
Disc Medicine said it expects initial data from the Phase 2 study of DISC-3405 in polycythemia vera (PV) in the fourth quarter of 2026, alongside a separate Phase 1b readout of the same drug in sickle cell disease. The trial, NCT06985147, is an open-label Phase 2 study enrolling adults who meet 2022 World Health Organization criteria for PV and have required frequent phlebotomy, a procedure to remove blood and lower red-cell mass. CEO John Quisel, J.D., Ph.D., said the company is "progressing ongoing" work on DISC-3405 in PV and sickle cell disease alongside a broader pipeline update in the company's first-quarter 2026 report. Disc+1Disc Medicine Reports First Quarter 2026 Financial Results and Provides Business UpdateMay 5, 2026A Phase 2, Open-Label Study of DISC-3405 in Participants With Polycythemia Vera (PV)NCT06985147
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What the readout will test
The trial's five registered primary endpoints cover the incidence of abnormal lab results, abnormal ECGs, abnormal physical exams, abnormal vital signs, and treatment-related adverse events graded by CTCAE, a standard toxicity grading scale. The measure most likely to shape how the readout is read, the proportion of participants achieving absence of phlebotomy eligibility during the maintenance and optimization periods, is registered as a secondary endpoint, alongside pharmacokinetic measures and changes in hematocrit, serum hepcidin, and serum iron. A Phase 2 open-label study without a control arm can establish tolerability and a directional efficacy signal; it is not built to prove a comparative effect. NCT06985147A Phase 2, Open-Label Study of DISC-3405 in Participants With Polycythemia Vera (PV)NCT06985147
Operational signal
The trial's enrollment target was revised once, from 20 to 60 patients, in November 2025, before the study moved from Not yet recruiting to Recruiting status in August 2025. That single amendment reflects a routine early-stage scope expansion rather than a change flagged by the trial's own operational thresholds, and the registry shows no further churn since. Sponsor guidance for the Q4 2026 data has held constant across disclosures issued in June 2025, January 2026, and May 2026, all pointing to the same fourth-quarter window. NCT06985147+1A Phase 2, Open-Label Study of DISC-3405 in Participants With Polycythemia Vera (PV)NCT06985147Disc Medicine Reports First Quarter 2026 Financial Results and Provides Business UpdateMay 5, 2026
Competitive position
No other antibody targeting TMPRSS6 has reached Phase 2 testing in polycythemia vera. The only other TMPRSS6-directed program on record, Ionis Pharmaceuticals' antisense oligonucleotide sapablursen, uses a different modality and has advanced to Phase 3 in PV under Ono Pharmaceutical. The broader PV and myeloproliferative-neoplasm field is populated mostly by JAK-inhibitor programs such as ruxolitinib, a different mechanistic class from hepcidin induction. With no validated disease-modifying alternative to phlebotomy and cytoreductive therapy in this setting, a result showing a meaningful share of patients reaching sustained absence of phlebotomy eligibility, without safety findings that complicate the tolerability profile, would be the outcome that distinguishes this readout from a routine early-phase update.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.