Press release
Fulcrum Therapeutics Announces Positive Interim Results from Phase 1 Healthy Adult Volunteer Trial of FTX-6058 for Sickle Cell Disease
Achieved dose proportional pharmacodynamic changes in HBG mRNA and F-reticulocytes in whole blood Mean 4.5-fold induction in HBG mRNA at 10mg after 14 days of
About this update from Fulcrum Therapeutics, Inc.
[{"type":"text","content":"Achieved dose proportional pharmacodynamic changes in HBG mRNA and F-reticulocytes in whole blood Mean 4.5-fold induction in HBG mRNA at 10mg after 14 days of once-daily dosingMean 4.2-fold increase in F-reticulocytes at 10mg after 14 days of once-daily dosing Achieved maximal target engagement by day seven in 6mg and 10mg cohorts FTX-6058 was generally well tolerated with no serious adverse events observed to dateCompany plans to initiate enrollment in a Phase 1b clinical trial in sickle cell patients in 4Q 2021Company plans to submit Investigational New Drug (IND) application in non-sickle cell hemoglobinopathies (e.g., beta-thalassemia) by year-end 2021Company to review clinical results on second quarter earnings call today at 8:00am ET CAMBRIDGE, Mass., Aug. 10, 2021 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc. (Nasdaq: FULC), a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases, today announced positive interim results from the ongoing single- and multiple-ascending dose (SAD and MAD) Phase 1 trial with FTX-6058 in healthy adult volunteers. FTX-6058 is an investigational, potent, and selective small molecule inhibitor of EED designed to increase the expression of fetal hemoglobin (HbF) with the potential to treat hemoglobinopathies, such as sickle cell disease and beta-thalassemia. Results from the MAD portion of the trial demonstrated proof of biology as evidenced by a dose proportional induction in HBG mRNA and accompanying increases in HbF-containing reticulocytes (F-reticulocytes). At 10mg, the highest dose studied to date, the mean changes were 4.5-fold and 4.2-fold, respectively. The increases in F-reticulocytes indicate that the HBG mRNA increases observed with FTX-6058 treatment are translating to HbF protein production. Additionally, all FTX-6058 doses in the MAD portion of the trial achieved maximal target engagement as evidenced by decreases in trimethylation at lysine 27 of histone H3 (H3K27me3), a downstream target of the polycomb repressive complex 2 (PRC2). These proof of mechanism results were achieved with once-daily, oral administration of FTX-6058 for 14 consecutive days, which was also generally well-tolerated in all SAD and MAD cohorts completed to date. “These results with FTX-6058 are very encouraging,” said Julie Kanter, MD, co...