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

Scientific rationale and mechanism of action

• Focus on neutralizing A-beta oligomers, which are highly toxic to synapses and drive neurodegeneration in Alzheimer's disease.

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

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

Clinical trial design and safety findings

• Phase I study in Alzheimer's patients established a wide dosing range up to 60 mg/kg to assess safety and target engagement.

• Five cases of ARIA-E observed, mostly at the highest dose, but overall safety profile considered favorable compared to historical agents.

• Dose response observed for target engagement, with plateauing at higher doses guiding phase II dose selection.

Target engagement and biomarker analysis

• Developed a sensitive ELISA-based assay to confirm sabirnetug binds oligomers in patient CSF.

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

• Phase I showed effects on multiple biomarkers, including amyloid, total tau, phospho-tau, and synaptic markers like VAMP2 and neurogranin.

• Observed biomarker changes suggest downstream effects on neurodegeneration and synaptic pathology.