Disc Medicine's TMPRSS6 antibody heads toward first sickle cell safety data
The Phase 1b readout will test whether hepcidin induction is tolerable in sickle cell disease, a mechanism with no direct clinical precedent in this population.
Executive Summary
- Disc Medicine is heading toward its first clinical readout testing whether inducing hepcidin through TMPRSS6 blockade is tolerable in patients with sickle cell disease, a mechanism the company has not yet tested in this population.
- The Phase 1b study is built to answer a safety and pharmacodynamic question, not an efficacy one, so the readout will show whether the drug is tolerable and whether it moves the blood markers the mechanism is designed to affect, not whether it changes clinical outcomes.
- No other industry trial targets TMPRSS6 in sickle cell disease, so the readout carries no head-to-head comparator and will be judged against the drug's own mechanistic rationale rather than a rival's result.
- The trial has held its enrollment target steady since posting and carries no protocol amendments to its endpoints or completion date, putting the disclosure timeline, not trial execution, at the center of the story.
The catalyst
Disc Medicine, Inc. expects initial data from its Phase 1b study of DISC-3405 in sickle cell disease in the fourth quarter of 2026, the company said in its first-quarter 2026 business update. The trial, registered as NCT07187973, is an open-label study enrolling adults with HbSC or HbSS sickle cell disease who have a history of disease-related complications. It is recruiting toward a target of 24 participants at seven United States sites. Disc+1Disc Medicine Reports First Quarter 2026 Financial Results and Provides Business UpdateMay 5, 2026A Phase 1b, Open-Label Study of DISC-3405 in Participants With Sickle Cell Disease (SCD)NCT07187973
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What the trial measures
The registered primary endpoint is the safety and tolerability of DISC-3405 in participants with sickle cell disease. Fourteen secondary endpoints cover pharmacokinetics and pharmacodynamic markers, including changes in hemoglobin, hematocrit, red blood cell count, reticulocyte count, lactate dehydrogenase, and bilirubin from baseline. DISC-3405 works by blocking TMPRSS6 to induce hepcidin, the hormone that regulates iron availability for red blood cell production, and the pharmacodynamic markers in this endpoint list are the readout's window into whether that mechanism is doing what it is designed to do in this population. NCT07187973A Phase 1b, Open-Label Study of DISC-3405 in Participants With Sickle Cell Disease (SCD)NCT07187973
Timing guidance
Disc Medicine has narrowed its guidance for this readout three times since November 2025, moving from a full-year 2026 window to a second-half 2026 window in January 2026, then to the fourth quarter of 2026 in its May 2026 update. The trial's own registered primary completion date is June 1, 2027, later than the guided readout window, reflecting that the company plans to disclose initial data before the study's formal completion rather than waiting for the full analysis. The trial has carried no amendments to its primary endpoint, enrollment target, or completion date since it began recruiting in December 2025. Disc+1Disc Medicine Reports First Quarter 2026 Financial Results and Provides Business UpdateMay 5, 2026A Phase 1b, Open-Label Study of DISC-3405 in Participants With Sickle Cell Disease (SCD)NCT07187973
The competitive frame
No other industry-sponsored trial tests TMPRSS6 blockade in sickle cell disease, making DISC-3405 the only in-class asset in this indication and phase. The closest mechanism-linked precedent is Ionis Pharmaceuticals' sapablursen, an antisense TMPRSS6 program tested in polycythemia vera rather than sickle cell disease, so no resolved trial shares both the target and this indication. Disc Medicine is running its own TMPRSS6 program in polycythemia vera in parallel, with data from that Phase 2 study also expected in the fourth quarter of 2026. The active sickle cell disease field is populated by mechanistically distinct programs, including Novartis's crizanlizumab, Novo Nordisk's etavopivat, Pfizer's osivelotor, Agios's mitapivat, and bluebird bio's gene therapy lovotibeglogene autotemcel, none of which target TMPRSS6 or hepcidin induction. DiscDisc Medicine Reports First Quarter 2026 Financial Results and Provides Business UpdateMay 5, 2026
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.