Fulcrum Therapeutics scrapped its lead sickle cell disease program, pociredir, and launched a comprehensive strategic review after FDA raised heightened concerns about malignancy risk tied to PRC2 inhibition. The agency’s position came after an end-of-phase meeting where Fulcrum received risk-and-benefit feedback. Fulcrum said no new safety signals had been observed in the program to date, but FDA concluded that malignancy risk associated with PRC2 targeting likely applies regardless of which PRC2 subunit is inhibited. Fulcrum’s decision follows a broader class shock after Ipsen’s tazemetostat (Tazverik) was voluntarily withdrawn from the market in March amid reports of secondary blood cancers emerging from its SYMPHONY-1 trial. With pociredir designed to inhibit EED to increase fetal hemoglobin (HbF), Fulcrum said it will discontinue development and consider options that could include selling assets or the entire business. The company is simultaneously looking to reduce operating expenses and preserve capital amid limited visibility into future value creation.