Fulcrum Therapeutics Announces Discontinuation of Pociredir Program in Sickle Cell Disease and Initiation of Strategic Review
― Decision follows FDA feedback regarding the implications of the secondary malignancies observed with Tazverik® (tazemetostat) and the product’s subsequent global withdrawal on the benefit-risk profile of pociredir in sickle cell disease (SCD) ―
― Company to explore strategic alternatives to maximize stockholder value ―
CAMBRIDGE, Mass., – June 1, 2026 – Fulcrum Therapeutics, Inc.® (Fulcrum) (Nasdaq: FULC), a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with rare hematological disorders, today announced the discontinuation of its pociredir program for the treatment of SCD and the initiation of a comprehensive review of strategic alternatives to maximize stockholder value.
On May 28, 2026, Fulcrum received meeting minutes from recent end-of-phase interactions with the FDA. The minutes reflected heightened FDA concerns regarding pociredir's benefit-risk profile in SCD, stemming from an unexpectedly high rate of secondary hematologic malignancies observed with Tazverik® (tazemetostat), another PRC2 inhibitor, which was withdrawn from the global market in March 2026. Fulcrum submitted information to FDA supporting the position that mechanistic differences between EED (pociredir's target) and EZH2 (tazemetostat's target), which perform different biological roles, were relevant to the benefit-risk assessment. FDA considered this position but concluded that any pharmacological intervention targeting the PRC2 complex carries equivalent malignancy risk regardless of the specific subunit engaged. FDA’s position is informed by pociredir's previously disclosed preclinical malignancy observations and left no viable regulatory path forward for further clinical development of pociredir.
“Following a thorough review of regulatory feedback, the totality of available data, and the implications for a viable regulatory path, we have made the very difficult decision to discontinue development of pociredir,” said Alex C. Sapir, Fulcrum’s President and Chief Executive Officer. “While no new safety signals have been observed to date with pociredir, the FDA raised concerns regarding the potential malignancy risk associated with pociredir’s inhibition of the PRC2 complex given the experience with Tazverik that was recently withdrawn from the market. We arrived at this decision after discussion with the FDA, and despite robust elevations in fetal hemoglobin seen with pociredir and the potential for clinical benefit, we do not see a path forward with pociredir. We know the SCD community has faced many disappointments and setbacks related to innovation for this devastating disease, and we are not only humbled but forever grateful to the SCD warriors, investigators, and broader SCD community who have worked tirelessly alongside Fulcrum to evaluate new treatment options for this devastating disease.”
Fulcrum will explore potential strategic alternatives, including, but not limited to, a merger, acquisition, business combination, or other strategic transactions involving the company or its assets. In connection with this review, Fulcrum has initiated efforts to significantly reduce its operating expenses and preserve capital. Fulcrum has not set a timeline for the completion of this review and does not intend to provide further updates unless and until the Board of Directors has approved a course of action, the review process is concluded, or other disclosure is otherwise determined to be appropriate.
As of March 31, 2026, Fulcrum had $333.3 million in cash, cash equivalents, and marketable securities.
About Fulcrum Therapeutics
Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with rare hematological disorders. Fulcrum’s lead clinical program was pociredir, a small molecule designed to increase expression of fetal hemoglobin (HbF) for the treatment of SCD. Fulcrum uses proprietary technology to identify drug targets that can modulate gene expression to treat the known root cause of genetically defined diseases. For more information, visit www.fulcrumtx.com and follow us on X (@FulcrumTx) and LinkedIn.
About Pociredir
Pociredir is an investigational oral small-molecule inhibitor of Embryonic Ectoderm Development (EED) that was discovered using Fulcrum’s proprietary discovery technology. Inhibition of EED leads to potent downregulation of key fetal globin repressors, including BCL11A, thereby causing an increase in HbF. Pociredir was being developed for the treatment of SCD. In the PIONEER Phase 1b clinical trial in people with SCD, pociredir has demonstrated dose-dependent increases in HbF, pan-cellular HbF induction, and improvements in markers of hemolysis and anemia. Across the 12 mg and 20 mg dose cohorts, pociredir has been generally well-tolerated with up to three months of exposure, with no treatment-related serious adverse events reported. Pociredir has been granted