Acumen presents topline results from first-in-human Phase 1 study of ACU193

Acumen Pharmaceuticals presented topline results from the Phase 1 INTERCEPT-AD trial of ACU193, the first clinical-stage AbetaO targeting antibody therapy in early AD, at the Alzheimer’s Association International Conference 2023, taking place in Amsterdam and online from July 16-20, 2023. Topline results demonstrated that ACU193 was generally well-tolerated with a compelling overall safety profile, meeting the primary objective of this Phase 1, first-in-human, randomized, double-blind, placebo-controlled study in both single and multiple doses in 60 participants with early AD. Dose levels were 2, 10, 25 and 60 mg/kg for one to three doses administered intravenously. An analysis of change in amyloid plaque load, as measured by positron emission tomography SUVr, demonstrated a rapid, dose-related mean decrease at the higher dose levels studied. This finding is comparable to mean amyloid plaque decreases of approved Ass monoclonal antibodies at similar time points in their clinical development. The overall rate of amyloid related imaging abnormalities – edema was 10.4%, which included one case of symptomatic ARIA-E. Pharmacokinetic results in serum and cerebrospinal fluid demonstrated statistically significant dose proportionality and support monthly dosing of ACU193. Statistically significant, dose-related central target engagement was observed as measured by ACU193-AssO complex, establishing the first target engagement assay developed that is specific to an AssO-targeting antibody. An exposure response relationship model revealed near maximal target engagement with repeated dosing at 25 mg/kg and 60 mg/kg. ACU193 Demonstrated Rapid, Dose-Related, Statistically Significant Amyloid Plaque Reduction Higher doses of ACU193 showed a statistically significant reduction in amyloid plaque load as determined by amyloid PET after 6-12 weeks. This finding provides evidence that ACU193 is active in the brain. ACU193 was well-tolerated throughout the single-ascending and multiple-ascending dose cohorts. Three treatment-emergent serious adverse events were observed after administration of ACU193; all were deemed not related or unlikely related to ACU193.