Fulcrum Therapeutics moved to discontinue its lead sickle cell disease program, pociredir, after the FDA raised concerns about the benefit-risk profile, including a link to unexpectedly high rates of secondary hematologic malignancies seen with Tazverik—a PRC2 inhibitor with similar target biology. The company said the regulator concluded that any PRC2-targeting intervention carried equivalent malignancy risk, eliminating a viable regulatory pathway. The decision triggered a major reorganization: Fulcrum later disclosed plans to lay off 85% of staff, shrinking its workforce to nine full-time employees as it seeks strategic alternatives. The move marks a sharp reversal following initial defense of the asset’s differentiation. The development will resonate across the PRC2 inhibitor class and broader gene-expression targeting strategies, reinforcing how safety signals from shared mechanism-of-action biology can reshape clinical and commercial timelines abruptly.