Acumen Pharmaceuticals, Inc. presented further analyses of the Phase 1 INTERCEPT-AD trial evaluating ACU193, the first clinical-stage AO-targeting antibody, at the 16(th) Annual Clinical Trials on Alzheimer's Disease (CTAD) conference in Boston and online. Acumen additionally presented new target engagement and pharmacokinetic (PK) analyses from clinical trial recruitment in four posters at the conference. Acumen plans to progress to a Phase 2/3 clinical study, with the Phase 2 portion planned to begin in the first half of 2024.

Results also demonstrated dose related plaque reduction, low overall ARIA-E and PK results supporting dosing of ACU193 every four weeks (Q4W), ultimately confirming proof-of-mechanism for the first clinical-stage monoclonal antibody designed to selectively bind AOs while potentially offering improved safety and clinical benefit over existing amyloid-directed therapies. Further analyses and data modeling of the robust Phase 1 dataset, presented at CTAD, shed deeper insights into the broad therapeutic potential of ACU193 and the clinical validity of targeting AOs, while helping to inform the subsequent Phase 2/3 study that will assess clinical efficacy. Modeleling the target engagement Emax curve offered the opportunity to select doses of 35 and 50 mg/kg with substantial target engagement of AOs for the Phase 2/3 study.

Amyloid plaque reduction results from the Phase 1 trial were also considered in the selection of 35 and 50 mg/kg doses, which will be evaluated versus placebo in the Phase 2/3 study". This finding demonstrates ACU193's activity in the brain and is a positive development given the relationship between robust amyloid reduction and slowing clinical decline established by other A-targeting antibodies. In further subgroup data, as presented by Dr. Stephen Salloway, M.D., M.S.,pert Medical School of Brown University, four of the five cases of ARIA-E occurred in APOE4 heterozygotes and none in APOE4 homozygotes.

INTERCEPT-AD: ACU193 CSF pharmacokinetics in the CSF was characterized by dose-proportional exposure in both the single- and multiple-dose cohorts, suggestive of ACU193's intended drug effect in the central nervous system (CNS). An ultra-sensitive assay developed to assess ACU193 drug concentration in the CNS of study participants confirmed that a decrease in ACU193 concentration in the CSF since last dose demonstrated drug clearance from the CNS over time. The full results of the INTERCEPT-AD study will be presented at a future medical congress and submitted for publication in a peer-reviewed clinical journal.

ACU193 has been granted Fast Track designation for the treatment of early Alzheimer's disease by the U.S. Food and Drug Administration.