Disc Medicine (IRON) 2024 European Hematology Association Congress summary

Clinical program updates

• Bitopertin Phase 2 trials (AURORA, BEACON) showed significant reductions in protoporphyrin IX (PPIX), improved light tolerance, and reduced phototoxic reactions, with up to 75%-92% reduction in pain events and twofold improvement in sunlight tolerance.

• DISC-0974 demonstrated dose-dependent, durable hepcidin reduction and iron mobilization in myelofibrosis patients, leading to increased hemoglobin and reduced transfusion burden, with 68% of non-transfusion-dependent patients showing a hemoglobin response.

• DISC-3405, an anti-TMPRSS6 antibody, showed dose-dependent hepcidin induction and over 50% reduction in serum iron in healthy volunteers, supporting monthly subcutaneous dosing and promising hematocrit control for polycythemia vera.

• All investigational agents were generally well-tolerated across evaluated dose levels, with no significant safety concerns reported.

• Mouse model data and clinical correlations support that PPIX reductions above 30%-40% are associated with marked improvements in photosensitivity and patient outcomes.

Forward-looking plans and regulatory strategy

• End-of-Phase 2 meeting for bitopertin is planned for the second half of 2024, with a pivotal trial targeted for the first half of 2025.

• Multiple viable endpoints, including longitudinal time in light and phototoxic reaction rates, will be proposed to regulators for future pivotal studies.

• DISC-0974 will advance to Phase 2 with cohort expansion in both non-transfusion-dependent and transfusion-dependent myelofibrosis patients, focusing on a single dose level.

• DISC-3405 will complete multiple ascending dose studies in 2024, with Phase 2 in polycythemia vera expected to start in the first half of 2025.

• Additional data from ongoing studies in chronic kidney disease and other indications are expected in the second half of 2024.

Industry context and Q&A highlights

• Bitopertin’s efficacy endpoints are closely aligned with regulatory precedents, and trial design will leverage robust endpoints to address placebo effects and optimize patient numbers.

• DISC-0974’s mechanism and efficacy are expected to translate to other inflammatory anemias, including chronic kidney disease, with dose adjustments as needed.

• The antibody approach for DISC-3405 is favored for its titratability and established safety profile compared to nucleic acid-based therapies.

• Enrollment strategies for myelofibrosis studies will adapt to include more transfusion-dependent patients as the program advances.

• The company anticipates a rich calendar of data readouts and trial initiations across its portfolio in late 2024 and 2025.