Fulcrum announces results from 20 mg dose cohort of Phase 1b PIONEER trial

Fulcrum Therapeutics (FULC) reported positive initial results from the ongoing 20 mg dose cohort of the Phase 1b PIONEER trial of pociredir in sickle cell disease, SCD. Initial results from the 20 mg dose cohort of the Phase 1b PIONEER trial are as follows: Mean absolute HbF increased by 9.9% at 6 weeks of treatment with pociredir, increasing from a baseline of 7.1% to 16.9%. As of the November 11, 2025 data cutoff, 7 of 12 patients achieved absolute HbF levels greater than or equal to20% at Week 6, and all patients demonstrated a robust HbF increase. HbF levels of 20% are associated with 90% of patients experiencing zero VOCs per year, based on real-world data presented by Fulcrum at the 20th Annual Sickle Cell & Thalassemia Conference in October 2025. A clear dose-response was observed, with a greater than3.75-fold mean induction of HbF at Week 12 among patients who reached the Week 12 visit as of the November 11, 2025 data cutoff, compared to a 2.4-fold mean induction at Week 12 in the 12 mg cohort. The average baseline for these six patients is 5.0% as compared to 7.1% for the full cohort. The proportion of F-cells increased from a mean of 31% at baseline to 58% at Week 6, indicating early progression toward pan-cellular HbF induction. Mean hemoglobin increased by 0.8 g/dL at Week , increasing from a baseline of 7.3 g/dL to 8.1 g/dL. A trend of reduced VOC frequency was observed relative to patients’ documented VOC frequency during the 6-12 months prior to enrollment. As of November 11, 2025 data cut off, eight of 12 patients reported no VOCs during the treatment period.