Acumen Pharmaceuticals (ABOS) Bank of America CNS Therapeutics Virtual Conference summary

Advances in Alzheimer's disease research and treatment

• Biomarkers for Alzheimer's can appear decades before symptoms, especially in ApoE4 carriers, supporting earlier intervention strategies.

• Recent approvals of disease-modifying therapies (lecanemab, donanemab) mark a turning point, shifting focus to optimizing intervention timing and efficacy.

• Early intervention in mild cognitive impairment and mild dementia populations is now possible, with future potential to treat preclinical cases.

• Fluid biomarkers are expected to play a growing role in identifying at-risk patients and guiding treatment regimens.

• The field is moving toward more personalized and earlier interventions as understanding of disease biology and biomarkers improves.

Sabirnetug's mechanism and clinical rationale

• Sabirnetug targets Aβ oligomers, believed to be early and potent instigators of Alzheimer's pathology, rather than monomers or plaques.

• The antibody demonstrates high selectivity (8,000-fold) for oligomers, minimizing off-target effects on normal amyloid forms.

• Early pharmacodynamic effects in phase I suggest potential for greater clinical benefit compared to current agents.

• Sabirnetug may offer both induction and maintenance therapy options, with flexibility in treatment regimens.

• Lower observed rates of ARIA in phase I, especially among E4 homozygotes, could provide a safety advantage.

Clinical development and trial progress

• The phase II ALTITUDE-AD study is a 540-patient, three-arm, placebo-controlled trial measuring cognitive decline over 18 months, with a 12-month open-label extension.

• Primary endpoint is iADRS, chosen for its sensitivity, with secondary cognitive and biomarker endpoints.

• Enrollment began in May 2024, with completion expected by mid-2025, reflecting strong site and participant enthusiasm.

• No interim analyses are planned to preserve the study's pivotal status for regulatory filing.

• The study design and size are intended to robustly detect treatment effects and inform future regulatory discussions.