Acumen Pharmaceuticals Presents First Comprehensive Clinical and Biomarker Data for Sabirnetug (ACU193) at American Academy of Neurology 2024 Annual Meeting - Seite 2

Sabirnetug Demonstrated Favorable Safety and Tolerability Profile

The poster outlines that sabirnetug demonstrated a favorable safety and tolerability profile in participants with early AD with a relatively low incidence of ARIA-E. There were four cases of asymptomatic ARIA-E and one symptomatic case among 48 participants who were treated with sabirnetug. Notably, none of the six participants who were APOE Ɛ4 homozygotes experienced ARIA-E despite making up 13% of all participants in the study. This contrasts with other studies of amyloid-targeting monoclonal antibodies where approximately 30 to 40 percent of participants who are APOE Ɛ4 homozygotes experienced ARIA-E.

Target Engagement

Sabirnetug target engagement with AβOs in cerebrospinal fluid (CSF) increased in a dose-dependent manner in both single and multiple ascending dose groups. Central target engagement approached the maximum at the highest doses of sabirnetug administered. The results suggest that at these dose levels, ACU193 concentrations approached saturation of AβOs, and suggests active removal of target from the brain.

Sabirnetug Associated with Changes in CSF and Plasma Biomarkers Indicating Downstream Effects on Amyloid, pTau Species, and Synaptic Markers After Three Administrations

Sabirnetug treatment also changed a number of CSF biomarkers in the multiple ascending dose cohorts, which are indicative of amyloid pathology (Aβ42/40 ratio), tau pathology (pTau181, pTau217), and synaptic injury (neurogranin, VAMP2). Sabirnetug significantly lowered CSF neurogranin (-13.9%), VAMP2 (-8.1%) and pTau181 (-13.0%) concentrations and numerically increased Aβ42/40 after three administrations of sabirnetug at 60 mg/kg once every 4 weeks (Q4W). Sabirnetug target engagement with AβOs was significantly correlated with reduction of CSF neurogranin. Additionally, plasma biomarkers for neuroinflammation (GFAP) and tau pathology (pTau181, pTau217) were lower in the 10 mg/kg Q4W and 60 mg/kg Q4W groups compared to placebo. Furthermore, nearly all patients treated with sabirnetug in the high dose multiple-ascending dose cohorts showed reductions in plaque load after three doses at 63 or 70 days. These results support sabirnetug’s proposed mechanism of action and intended target engagement of synaptotoxic AβOs.