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Safety, Tolerability, Pharmacokinetics, and Brain Target Occupancy of the OGA Inhibitor ASN90 in Healthy Participants
Rolf Pokorny1, J Michael Ryan1, Khalid Abd-Elaziz2
1Asceneuron SA, EPFL Innovation Park, Bâtiment B, Lausanne, Switzerland.
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.
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