In vitro and in vivo preclinical pharmacokinetic characterization of ulacamten, a small molecule cardiac myosin inhibitor for the treatment of heart failure with preserved ejection fraction (HFpEF)

included CYP-mediated deformylation (metabolite M1) and hydroxylation of the methyl group of the methylcyclohexyl moiety (metabolite M2).The predicted human pharmacokinetic parameters clearance (CL), steady-state volume of distribution, and half-life were 4.5 mL/min/kg, 5.8 L/kg, and 14.9-hours, respectively, determined from an average of multiple prediction methods.Ulacamten preclinical attributes and predicted human pharmacokinetic parameters allowed for its progression to clinical development.