Acumen Pharmaceuticals, Inc. (NASDAQ: ABOS) has announced the publication of the Phase 1 INTERCEPT-AD study results in the Journal of Prevention of Alzheimer’s Disease, marking a significant milestone in the development of its novel therapeutic, sabirnetug (ACU193). The study, a robust, U.S.-based, multi-center, randomized, double-blind, placebo-controlled clinical trial, evaluated the safety, tolerability, and efficacy of sabirnetug in patients with early Alzheimer’s disease (AD). The results demonstrated sabirnetug's potential as a next-generation antibody treatment for early symptomatic AD.

Sabirnetug, a humanized monoclonal antibody, selectively targets and inhibits toxic soluble amyloid beta oligomers (AβOs), preventing them from binding to synapses and preserving neuronal function. The INTERCEPT-AD study results showed that sabirnetug was generally well-tolerated, with no drug-related serious adverse events reported. The overall rate of amyloid-related imaging abnormalities with edema (ARIA-E) was 10.4%, with only one case of mildly symptomatic ARIA-E (2.1%) that resolved within four weeks. Notably, no ARIA-E was observed in APOE homozygotic participants, and four of the five cases of ARIA-E were in APOE heterozygotes.



The study also demonstrated rapid, direct target engagement of AβOs in a dose-proportional manner, changes in biochemical biomarkers in cerebrospinal fluid (CSF), and statistically significant amyloid plaque reduction within higher multiple-ascending-dose (MAD) cohorts. Sabirnetug showed normalizing trends in the multiple ascending dose cohorts on CSF levels of AD biomarkers such as p-tau181, p-tau217, total tau, and the Aβ42/Aβ40 ratio, as well as synaptic biomarkers VAMP2, neurogranin, and neuropentraxin 2. These findings are consistent with downstream pharmacodynamic effects of sabirnetug after just three administrations and with its mechanism of action and target engagement of synaptotoxic AβOs.



The publication of the INTERCEPT-AD study results in the Journal of Prevention of Alzheimer’s Disease is a significant milestone in Acumen's ongoing clinical development of sabirnetug. The robust data package generated by this Phase 1 study provides important evidence of sabirnetug's safety profile, further confirms its mechanism of action, and establishes the foundation for the ongoing Phase 2 ALTITUDE-AD clinical trial. The doses used in the ALTITUDE-AD trial are based on the results of the INTERCEPT-AD study, and Acumen expects to complete enrollment in the first half of 2025.

Acumen is developing sabirnetug as a potential best-in-class antibody treatment for early symptomatic AD. The company's commitment to advancing the collective understanding of Alzheimer's disease pathology and developing a next-generation treatment for this burdensome disease is evident in its ongoing clinical development efforts. As the Phase 2 ALTITUDE-AD trial progresses, investors and analysts will closely monitor the specific biomarkers and clinical endpoints discussed in this article to evaluate sabirnetug's efficacy and potential impact on the AD treatment landscape.

In conclusion, the publication of the Phase 1 INTERCEPT-AD study results in the Journal of Prevention of Alzheimer’s Disease supports Acumen's continued development of sabirnetug for the treatment of early Alzheimer’s disease. The study's findings demonstrate sabirnetug's potential as a next-generation antibody treatment for early symptomatic AD, with a favorable safety profile and encouraging efficacy data. As the Phase 2 ALTITUDE-AD trial continues, investors and analysts will closely monitor the study's progress and the potential impact of sabirnetug on the AD treatment market.