RESULTS FROM A 3-MONTH STUDY IN HEALTHY SUBJECTS AGED 60 YEARS WITH THE BACE INHIBITOR CNP520

The BACE inhibitor CNP520 is under clinical development as a potential disease-modifying treatment in asymptomatic subjects at risk for Alzheimer's disease. A 3-month dose-ranging safety and tolerability study in healthy subjects ≥60 years of age has been conducted. Safety, tolerability, pharmacokinetics (PK) and CSF Aβ reduction were investigated. This Phase IIa study was a randomized, double-blind, five arm-parallel-group, placebo controlled study to evaluate four doses of CNP520 (2 mg, 10 mg, 35 mg or 85 mg q.d.) compared to placebo over a 3-month exposure duration in healthy subjects ≥60 years of age. Safety and tolerability were assessed based on adverse event (AE), laboratory, vital sign, ECG, cognitive tests, ophthalmological and dermatological evaluations. CNP520 and Aβ concentrations were quantified in plasma and CSF. CNP520 was safe and well tolerated at all doses tested. There was no major imbalance of AEs between CNP520 and placebo except for skin and subcutaneous tissue disorders that occurred at higher incidence on CNP520 than on placebo (18.0% versus 4.2%), with no evidence of dose dependency. The imbalance was mainly due to events of pruritus that were mostly mild and transient, except for a single longer-lasting event of moderate severity. CSF Aβ concentrations were reduced in a dose-dependent manner up to 91% compared to baseline after 3-month exposure and stable over time. The pharmacokinetics of CNP520 was characterized by dose-proportional increase in plasma exposure. T1/2 was approximately 150 h, supporting daily dose administration. Safety, tolerability, PK and pharmacodynamic data obtained in this 3-months study in healthy subjects ≥60 years of age support further development of CNP520 in cognitively unimpaired individuals at risk for Alzheimer's disease.