Acumen Pharmaceuticals (ABOS) 12th Annual Cantor Fitzgerald Global Healthcare Conference summary

Company overview and pipeline milestones

• Focused on advancing treatments for early Alzheimer's disease, with sabirnetug as the lead monoclonal antibody targeting toxic A-beta oligomers, aiming for phase II proof-of-concept data by late 2024.

• Enhanced Brain Delivery (EBD) program leverages JCR Pharmaceuticals' transferrin receptor-mediated technology to improve CNS delivery, with IND filing targeted for mid-2027.

• Two EBD candidates, ACU301 (sabirnetug cargo) and ACU401 (ACU234 cargo), are in IND-enabling development, with a lead candidate to be selected for phase I.

• Retention and enrollment in the ALTITUDE phase II study have exceeded expectations, with over 95% rollover into open-label extension.

• Key value-creating goals include validating the oligomer hypothesis in ALTITUDE and dosing the first EBD patient in 2027.

Scientific rationale and mechanism of action

• Sabirnetug is highly selective for A-beta oligomers, believed to be the most neurotoxic species in Alzheimer's, with 10,000-fold selectivity over monomers and 100-fold over fibrils.

• The oligomer hypothesis posits that targeting soluble A-beta oligomers could yield earlier or more robust cognitive benefits compared to plaque-directed therapies.

• Phase I data demonstrated target engagement, dose response, and favorable safety, with low ARIA rates and positive biomarker shifts in imaging and fluid markers.

• Synaptic markers such as neurogranin and VAMP2 showed promising changes, suggesting network-level effects.

• The field is rapidly evolving with new biomarkers, enhancing the ability to monitor and optimize therapeutic strategies.

Clinical development and study design

• ALTITUDE phase II is a three-arm, placebo-controlled, 18-month study with 542 subjects, using iADRS as the primary endpoint and CDR Sum of Boxes as secondary.

• Doses of 35 and 50 mg/kg every four weeks were selected based on phase I dose-response and biomarker data.

• Study is powered to detect meaningful cognitive changes, with rapid enrollment and strong patient retention.

• ARIA was observed in phase I, mostly at the highest dose, with no ARIA-E in E4 homozygotes; ongoing monitoring in phase II will further inform safety.

• A 30% or greater slowing on iADRS versus placebo is considered a clear win, benchmarking against approved agents.