Acumen Pharmaceuticals (ABOS) investor relations material

Program overview and scientific rationale

• Lead program sabirnetug is a humanized monoclonal antibody targeting soluble toxic Aβ oligomers, aiming to differentiate on safety and efficacy in Alzheimer's disease.

• Sabirnetug is in a phase II study (ALTITUDE-AD) with results expected late this year.

• Oligomer-directed approaches are believed to offer improved efficacy and safety over plaque-directed therapies.

• Targeting Aβ oligomers is based on their role as potent neurotoxins, distinct from non-toxic monomers.

• The company is also developing enhanced brain delivery (EBD) programs using receptor-mediated transcytosis, aiming for an IND milestone in mid-2027.

Clinical data and trial progress

• INTERCEPT-AD phase I study showed robust target engagement, dose-proportional effects, and positive biomarker changes, supporting advancement to phase II.

• Imaging and fluid biomarkers, including amyloid PET and synaptic markers, showed promising results at higher doses.

• ALTITUDE-AD phase II is a robust, placebo-controlled study with two active doses, enrolling 542 patients across five countries.

• The primary endpoint is iADRS, with a target of 30% slowing over 18 months; high conversion rates to open-label extension observed.

• Study conduct and early terminations have aligned with expectations.

Enhanced brain delivery and partnerships

• Collaboration with JCR Pharmaceuticals leverages their transferrin-directed delivery technology, validated in other indications.

• Enhanced brain delivery has shown 14–40x higher cortical drug levels in non-human primates compared to unmodified antibody.

• Broader and more diffuse brain distribution is expected to synergistically improve therapeutic outcomes.

• Two candidates, sabirnetug and ACU-234, are being advanced, with IND filing planned for mid-2027.

• JCR’s approach has not shown anemia, addressing a key safety concern with transferrin receptor targeting.