Acumen Pharmaceuticals Presents Sabirnetug (ACU193) Fluid Biomarker and Target Engagement Analyses from Phase 1 INTERCEPT-AD Study in Early Alzheimer’s at the AD/PD 2024 Annual Meeting - Seite 2

Sabirnetug had an observed dose-dependent trend in the multiple ascending dose cohorts on CSF levels of pTau181, pTau217 total tau, neurogranin and the Aβ42/Aβ40 ratio, consistent with the downstream pharmacologic effects after just three administrations of the drug. Key findings include:

• Improvements in biomarkers associated with AD pathology, including significantly lowered CSF levels of neurogranin (-13.9%) and pTau181 (-13.0%) and trending toward an increasing Aβ42/40 ratio using 60 mg/kg Q4W as compared to the placebo group;
• A nominally significant correlation between target engagement of AβOs and change in neurogranin across all doses, supportive of drug effect; and
• A trend in correlation between target engagement of AβOs and change in p-tau181 across all doses, also supportive of drug effect.
  

These findings support a biological link between sabirnetug and neurogranin and pTau181 and are consistent with sabirnetug’s proposed mechanism of action and intended target engagement of AβOs, as sabirnetug’s effects on these two biomarkers are more closely related to binding of AβOs than plaque reduction.

“We’re thrilled to return to AD/PD this year since completing the Phase 1 INTERCEPT-AD trial with results from our biomarker assessment, which further validate our confidence in sabirnetug’s proposed mechanism of action,” said Daniel O’Connell, Chief Executive Officer of Acumen. “As the Alzheimer’s treatment landscape continues to evolve, we’re seeing just how important biomarkers are to better characterize and understand the underlying pathology of disease, and we look forward to exploring the relationship between these biomarkers and clinical outcomes in a longer-term Phase 2 study.”

Target Engagement in INTERCEPT-AD: Development of a Novel Assay Measuring Sabirnetug (ACU193)-Amyloid Beta Oligomer Complexes in Human CSF

Additionally, Acumen presented a poster detailing its method to develop the first assay to directly measure target engagement of AβOs by an immunotherapy (as measured by sabirnetug-AβO complex in CSF) in the INTERCEPT-AD trial. The novel assay configuration was tailored to selectively detect sabirnetug-AβO complex in CSF as a direct measure of target engagement, showing clear dose-related increases in target engagement across all cohorts. This data also informed development of a pharmacokinetic-pharmacodynamic (PK/PD) model, which ultimately demonstrated that the highest doses used in INTERCEPT-AD (60 mg/kg Q4W and 25mg/kg Q2W) approached maximal target engagement, as was presented in October 2023.