DISC-0974 (anti-hemojuvelin; hepcidin-lowering) drives 50–71% anemia responses in Phase 2 myelofibrosis

DISC-0974 is a first-in-class monoclonal antibody that blocks hemojuvelin (HJV) to suppress BMP-pathway–driven hepcidin and improve iron availability for erythropoiesis. In the US open-label Phase 2 RALLY-MF study (NCT05320198), adults with primary/secondary MF and anemia were treated with DISC-0974 50mg SC monthly (up to 6 doses; option to escalate to 75mg), including patients on stable JAK inhibitor therapy; at the Oct 16, 2025 data cut, 47 patients were enrolled (nTD n=30; TD-low n=10; TD-high n=7; 53% on concomitant JAKi) and hematologic responses among evaluable patients were 50% achieving ≥1.5g/dL Hgb increase for ≥12 weeks (nTD), 71% achieving transfusion independence for ≥16 weeks (TD-low), and 67% achieving ≥50% transfusion-burden reduction (TD-high), alongside sustained hepcidin reduction/iron mobilization and improved FACIT-Fatigue in nTD/TD-low. Safety looked clean in this early snapshot (9 SAEs; 16 ≥G3 AEs, all deemed unrelated; no AE-driven early withdrawals); benchmark-wise, approved momelotinib (JAK1/2 + ACVR1 inhibitor) has shown ~66.5% transfusion independence at week 24 in SIMPLIFY-1 (vs 49.3% with ruxolitinib), while danazol historically delivers anemia response rates in the ~30% range in MF—so DISC-0974’s transfusion and Hgb signals look competitive for a hepcidin-axis, non-JAK approach, albeit with smaller n and different endpoint definitions/time windows.