Fulcrum Therapeutics’ sickle cell disease program based on PRC2 inhibition was discontinued in June 2026 after heightened regulatory concern. The company’s oral EED-binding inhibitor, pociredir (FTX-6058), was designed to link PRC2 inhibition to induction of fetal hemoglobin (HbF), following a mechanism explored widely in oncology. Fulcrum cited clinical proof of concept and robust HbF induction from Phase 1b, but said the withdrawal of the PRC2 inhibitor tazemetostat triggered additional regulatory scrutiny related to secondary hematologic malignancy risk. The termination illustrates the regulatory sensitivity of epigenetic approaches in hematologic contexts and how external program-level safety signals can cascade into program decisions—even after early biological activity in targeted populations.