Distinguishing between amyloid‐beta‐directed antibodies: Ability of PMN310 to target toxic oligomers despite competing species

A large body of evidence indicates that the most pathogenic species of Abeta in Alzheimer’s disease (AD) consist of soluble toxic oligomers as opposed to insoluble fibrils and monomers. The ability of a therapeutic antibody to target toxic Abeta oligomers without being diverted by binding to competing non‐toxic species is expected to result in greater efficacy. This is supported by clinical results to date showing poor efficacy of non‐selective antibodies but improved success with partially selective antibodies that bind oligomers and plaque. As a next generation antibody, PMN310 is a therapeutic candidate designed to more selectively target toxic oligomers. Avoiding interaction with plaque and vascular deposits has the additional advantage of potentially decreasing the incidence of amyloid‐related imaging abnormalities (ARIA). In this study, PMN310 was compared to other Abeta antibodies for selectivity and ability to maintain interaction with toxic oligomers in the presence of competing monomers.