Safety, Tolerability, Pharmacokinetics, and Brain Target Occupancy of the OGA Inhibitor ASN90 in Healthy Participants

Abstract Background The OGA inhibitor ASN90/FNP‐223 has the potential for disease modification in neurodegenerative diseases. A phase 1 clinical program in healthy participants was performed to determine its suitability for subsequent studies in movement disorders and Alzheimer's disease (AD) patients. Methods Clinical Study 1: A randomized, double‐blind, placebo‐controlled, first‐in‐human study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and food effect of single and multiple doses of orally administered ASN90 in healthy adult and elderly participants. Clinical Study 2: A phase 1, open‐label, positron emission tomography (PET) study in healthy participants to determine the relationship between plasma concentration and brain target occupancy of ASN90 following a single oral dose. Objectives To assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and central nervous system (CNS) target engagement of ASN90 in healthy participants. Results ASN90 was considered safe and well tolerated with dose‐proportional pharmacokinetics at steady‐state up to oral doses of 500 mg twice daily. Cerebrospinal fluid‐to‐plasma ratios for mean peak and mean systemic exposures were in the range of 2.5%–4.6%. Investigation of CNS occupancy using a PET ligand demonstrated that target occupancy of greater than 98% in the brain of healthy participants can be achieved at doses that are clinically well tolerated. Conclusions The phase 1 results of ASN90 in healthy participants provide strong support for its further development in progressive supranuclear palsy (PSP) and AD. Currently, Ferrer Internacional, S.A. is conducting a phase 2 study, known as PROSPER (ClinicalTrials.gov ID: NCT06355531), to evaluate the efficacy, safety, and pharmacokinetics of ASN90 in slowing the progression of PSP. © 2025 International Parkinson and Movement Disorder Society.