ProMIS Neurosciences Inc. announced the publication of a paper titled, ?Relationship between therapeutic activity and preferential targeting of toxic soluble aggregates by amyloid-beta-directed antibodies," in the online journal, bioRxiv. The study characterized and compared the binding profile of various amyloid-beta (Ab)-directed antibodies to monomers, soluble oligomers and insoluble Ab fibrils. The results indicate that selectivity for soluble toxic Aß oligomers may be a driver of clinical efficacy and indicated that PMN310 displayed the greatest degree of oligomer selectivity.

PMN310, the Company?s novel monoclonal antibody being evaluated as a treatment for Alzheimer?s disease (AD), is currently undergoing Phase 1a clinical studies in healthy volunteers, with initial safety and pharmacokinetic data expected in mid-2024. Aß-directed antibodies tested clinically for therapeutic activity against AD have shown varying degrees of efficacy. A side-by-side comparison of antibody binding to different molecular species of Aß conducted by ProMIS provided insight into the observed variability in clinical outcomes.

A correlation was observed between reported clinical efficacy and the ability of an antibody to retain binding to soluble oligomers from AD brains when faced with monomer competition. PMN310 showed a high degree of resistance to monomer competition. Importantly, unlike all other antibodies tested, PMN310 also avoided binding to plaque and vascular deposits of Ab.

Consequently, PMN310, may reduce the risk of brain edema (ARIA-E) and microhemorrhages (ARIA-H) often associated with plaque-binding antibodies. This premise is supported by the results showing that weekly dosing of a murine version of PMN310 at very high doses (800 mg/kg) for 26 weeks in a mouse model of AD did not cause any detectable brain hemorrhages upon microscopic examination.