ProMIS Neurosciences presents in vitro preclinical data on PMN310

ProMIS Neurosciences presented new in vitro preclinical data supporting the differentiation of PMN310 from other amyloid-beta-directed antibodies at the International Conference on Alzheimer’s and Parkinson’s Disease and Related Neurological Disorders. Antibody therapies that target Abeta in AD continue to generate interest with recent approvals and new potential treatments in development. A large body of evidence suggests that soluble toxic Abeta oligomers, rather than Abeta monomers or plaque, are the principal driver of synaptic dysfunction, neuronal loss and cognitive decline in AD patients. However, it has been a challenge to specifically target toxic oligomers since they are the least abundant form of Abeta in the brain. In preclinical studies, ProMIS Neurosciences’ lead candidate, PMN310, has demonstrated its ability to selectively target pathogenic Abeta oligomers without unproductive binding to non-toxic monomers or plaque. In a poster presentation titled, "Differentiation of PMN310 from other amyloid-beta-directed antibodies: Ability to selectively target toxic brain oligomers despite competing monomers and plaque," surface plasmon resonance was used to assess the binding of multiple Abeta-directed antibodies to a toxic oligomer-enriched low molecular weight fraction of soluble brain extract from AD patients, with and without pre-exposure to competing monomers. The antibodies that best avoided monomer competition and retained measurable binding to AD brain toxic oligomers have also generated positive results in clinical trials. Antibodies that could not overcome monomer competition have produced negative clinical trial results. In this side-by-side comparison in a nonclinical assay, PMN310 was the least impacted by monomer competition, resulting in an overall greater toxic oligomer binding level versus all comparators. Further, in contrast to the other Abeta-directed antibodies, PMN310 did not bind to plaque or vascular deposits in AD brain, suggesting that it may carry a reduced risk of dose-limiting ARIA side effects associated with plaque-binding antibodies.