ABSTRACT
SAD
FUNGAL INFECTIONS
The authors declare a conflict of interest. M.R.H., E.O., and P.W. were employees of Amplyx (now a Pfizer Inc., subsidiary). M.R.H. was previously an employee of Pfizer and holds Pfizer stock and is currently a consultant for Pfizer. A.J. and M.T. are Pfizer employees and hold Pfizer stock. S.v.M. and E.-J.v.H. are employees of ICON (former PRA Health Sciences). K.J.S. was previously an employee of Amplyx and is now an independent consultant at Hearts Consulting Group, LLC. W.G.K. was a paid consultant to Amplyx with respect to these studies.Fosmanogepix (FMGX, APX001), a first-in-class, intravenous (i.v.) and oral (p.o.) antifungal prodrug candidate is currently in clinical development for the treatment of invasive fungal infections. Manogepix (MGX, APX001A), the active moiety of FMGX, interferes with cell wall synthesis by targeting fungal glycosylphosphatidylinositol-anchored cell wall transfer protein 1, thereby causing loss of cell viability. Data from two phase 1, placebo-controlled, single-ascending dose (SAD) and multiple-ascending dose (MAD) studies evaluating safety, tolerability, and pharmacokinetics of FMGX (doses up to 1,000 mg, i.v. and p.o.) are presented. Eligible participants were healthy adults (aged 18 to 55 years) randomized to receive either FMGX or placebo. Across both phase 1 studies, 151 of 154 participants (aged 23 to 35 years; FMGX: 116, placebo: 38) completed the study. Administration of FMGX i.v. demonstrated linear- and dose-proportional pharmacokinetics of MGX in terms of geometric mean maximum concentration of drug in serum (