Acumen Pharmaceuticals, Inc. has published new findings from its Phase 1 INTERCEPT-AD study of sabirnetug (ACU193).

The research highlights the experiences of patients in the clinical trial to inform development of future trials, biomarker data to support sabirnetug’s mechanism of action, and an ultra-sensitive method of measuring small amounts of sabirnetug in cerebrospinal fluid (CSF). The posters will be presented at the Alzheimer’s Association International Conference (AAIC) 2024 taking place in Philadelphia and online from July 28 to August 1, 2024.

Sabirnetug is the first humanized monoclonal antibody to demonstrate in patients with early symptomatic AD selective target engagement of AβOs, a soluble and highly toxic form of Aβ that accumulates early in AD and is a persistent trigger of synaptic dysfunction and neurodegeneration. Acumen is developing sabirnetug as a potential best-in-class antibody treatment for early symptomatic AD.

“These findings from our Phase 1 study of sabirnetug highlight not only the strength of the study design with participants having early symptomatic AD but also continue to support the potential for sabirnetug as a best-in-class treatment," said Eric Siemers, MD, Chief Medical Officer of Acumen.

“Our research reflects our focus on incorporating the patient voice into drug development, provides further support for the mechanism of action of sabirnetug, and includes developing powerful tools for drug development with an assay that can measure even small amounts of sabirnetug bound to toxic soluble amyloid beta oligomers in patients in our clinical trials. These insights can help us as we advance clinical studies of sabirnetug, including our ongoing Phase 2 study. As recently approved therapies for Alzheimer’s gain traction, we have an opportunity to advance a next-generation treatment that has the potential to optimize the benefit-risk ratio compared to first-generation disease-modifying treatments for AD,” Siemers added.

Acumen is putting patients first by incorporating the patient voice in drug development. Acumen conducted exit interviews in a subset of patients from the INTERCEPT-AD trial to understand their experience with MCI and mild AD and expectations for treatment. Acumen also obtained feedback on topics such as the decision-making process preceding trial enrollment and the overall trial experience, and examined the results by participant gender to guide planning for future clinical trials.

Participants reported a broad array of symptoms consistent with AD, most frequently difficulty with memory or cognitive functioning. Nearly every participant desired treatment that would keep the disease from getting worse or slow progression. Additionally, participants wanted a new treatment that would help them maintain the ability to recognize loved ones and maintain or improve communication abilities.

The study revealed that three administrations of sabirnetug significantly lowered CSF levels of both pre- and post-synaptic proteins, consistent with its proposed mechanism of action to inhibit synaptic binding of AβOs. VAMP2, a biomarker associated with synaptic injury, was significantly lowered in all multiple ascending dose cohorts and appeared to be the biomarker most sensitive to sabirnetug in this study. Acumen is planning to evaluate longer-term changes in biomarkers and their relationship to clinical outcomes in the ongoing 18-month Phase 2 clinical trial ALTITUDE-AD to further support sabirnetug’s mechanism of action.