Acumen Pharmaceuticals (ABOS) H.C. Wainwright 26th Annual Global Investment Conference 2024 summary

Scientific rationale and mechanism of action

• Focus on neutralizing toxic A-beta oligomers, which are highly toxic to synapses and drive neurodegeneration.

• Chronic treatment with agents targeting soluble aggregates like protofibrils shows ongoing patient benefit.

• Targeting oligomers, rather than monomers or plaques, may unlock greater safety and efficacy.

• Oligomeric aggregates bind to neurons at synapses, causing circuit disruption and tau phosphorylation.

Clinical trial design and safety findings

• Phase I study in Alzheimer's patients established safety, target engagement, and biomarker effects.

• Five cases of ARIA-E observed among 48 patients, mostly at the highest dose; symptomatic ARIA is the main clinical concern.

• Dose response observed for target engagement, with a plateau effect at higher doses.

• Phase II study uses 50 mg/kg and 35 mg/kg dosing every two weeks, informed by phase I results.

Target engagement and biomarker analysis

• Developed a fit-for-purpose ELISA assay to measure drug-oligomer complexes in CSF.

• Significant target engagement observed at 10, 25, and 60 mg/kg doses, with a plateau at higher doses.

• Biomarker analysis showed effects on amyloid, total tau, phospho-tau, and synaptic markers like VAMP2 and neurogranin.

• High-dose levels showed significant effects on phospho-tau 181 and neurogranin.