Acumen Pharmaceuticals (ABOS) R&D Day 2024 summary

Strategic vision and market opportunity

• Focus on developing sabirnetug, a next-generation antibody targeting toxic A-beta oligomers in early Alzheimer's disease, aiming for improved efficacy and safety over current anti-amyloid therapies.

• The early AD population is growing due to aging demographics and better diagnostics, with an estimated 7 million affected in the U.S. and over 50 million globally, expected to triple by 2050.

• Recent regulatory and payer advances, including FDA fast track designation and Medicare coverage for amyloid PET scans, support the clinical and commercial pathway.

• Partnership with Halozyme to develop a subcutaneous formulation of sabirnetug, with phase I results expected in Q1 2025, aims to enhance patient convenience and market reach.

• Cash and marketable securities of $281M as of June 30, 2024, provide projected runway into the first half of 2027, supporting ongoing and planned clinical development.

Scientific rationale and clinical differentiation

• Sabirnetug is highly selective for soluble A-beta oligomers, believed to be the most toxic species in AD, with lower affinity for monomeric A-beta compared to other antibodies.

• Preclinical studies show sabirnetug rescues synaptic plasticity and reduces synaptic loss, with evidence of target engagement and functional benefit in animal and human tissue models.

• Phase I INTERCEPT-AD trial demonstrated dose-proportional target engagement, amyloid lowering (20-21% reduction), and favorable pharmacokinetics.

• Fluid biomarker data showed improvements in A-beta 42/40 ratio, reductions in p-Tau181 and p-Tau217, and positive effects on synaptic markers VAMP2 and neurogranin after only three doses.

• ARIA incidence was low and mostly asymptomatic; notably, no ARIA was observed in E4 homozygotes, a high-risk group, though further validation is needed in larger studies.

Clinical development and future plans

• Phase II ALTITUDE-AD trial is ongoing in North America and Europe, with enrollment expected to complete in the first half of 2025 across 70 sites.

• The trial features two active dose arms plus placebo, open-label extension, and broad eligibility (including patients up to 90 years old), designed to maximize patient access and data quality.

• No public interim analyses are planned for phase II; top-line subcutaneous phase I data expected Q1 2025.

• Biomarker-driven screening (p-Tau prior to PET) has improved trial efficiency, reducing unnecessary scans by 50%.

• Subcutaneous formulation aims for no more than a single weekly injection, leveraging Halozyme's ENHANZE technology.