Acumen Pharmaceuticals (ABOS) R&D Day 2024 summary

Strategic Focus and Market Opportunity

• Targeting early Alzheimer's disease, a population of ~7 million in the US, with prevalence expected to grow due to aging and improved diagnosis.

• Emphasis on differentiated approach by targeting toxic amyloid beta oligomers, supported by decades of research and CNS drug development expertise.

• Recent regulatory advances and clinical validation of anti-amyloid therapies have established a pathway for next-generation treatments.

• Partnership with Halozyme to develop a subcutaneous formulation, aiming for greater patient convenience and optionality, with topline results from a healthy volunteer study expected in Q1 2025.

• Focus on expanding treatment options for the growing Alzheimer's population, leveraging a team with extensive CNS/AD drug development experience.

Scientific Rationale and Preclinical Data

• Sabirnetug is a humanized monoclonal antibody with high selectivity for soluble A-beta oligomers, believed to be key neurotoxins in AD.

• Preclinical studies show sabirnetug binds multiple oligomer species, neutralizes synaptic toxicity, and rescues synaptic plasticity.

• Demonstrated high selectivity for oligomers over monomers, with ~8,000-fold preference, differentiating it from other antibodies.

• Chronic administration in animal models increased postsynaptic density and reduced amyloid deposition, especially in younger animals.

• Oligomer targeting may offer benefits in both efficacy and safety, particularly for high-risk subpopulations like APOE4 carriers.

Clinical Development and Trial Results

• Phase I INTERCEPT-AD trial showed dose-proportional target engagement, significant amyloid plaque reduction, and favorable pharmacokinetics.

• Five cases of ARIA were observed, all resolved without serious outcomes; notably, no ARIA in E4 homozygotes, a key high-risk group.

• Biomarker analysis revealed dose-dependent improvements in A-beta 42/40 ratio, reductions in p-Tau181 and p-Tau217, and positive effects on synaptic markers VAMP2 and neurogranin.

• Duration of dosing influenced biomarker response, supporting the design of the ongoing 18-month phase II ALTITUDE-AD trial, which uses higher, monthly IV doses (35mg/kg and 50mg/kg Q4W).

• ALTITUDE-AD Phase 2 trial is enrolling globally across 70 sites, with completion of enrollment expected in the first half of 2025.