Fulcrum Therapeutics ended development of its sickle cell disease candidate pociredir and launched a strategic review after the FDA raised heightened concerns about malignancy risk for PRC2 inhibitors. The company cited risk signals drawn from Ipsen’s previously withdrawn tazemetostat (Tazverik) program, where secondary blood cancers emerged in trial settings. Fulcrum said no new safety signals have been observed to date with pociredir, but FDA staff concluded the risks could not be differentiated by mechanistic subunit engagement and that there was no viable regulatory path forward. The biotech is now exploring potential mergers or sales of assets or the company. The decision follows an end-of-phase interaction that left the program without a clear path to later-stage development. Fulcrum’s rationale centered on EED-targeting PRC2 inhibition intended to increase fetal hemoglobin, but regulatory risk assessment overrode the benefit-risk framing. The move highlights how safety lessons from the broader PRC2 inhibitor class can cascade across development programs—particularly in hematology where long-term malignancy risk assessment is tightly scrutinized.