ProMIS Neurosciences to Present PMN310’s Targeting of Toxic Oligomers at Cognitive & Behavioral Neurosciences Conference

ProMIS Neurosciences Inc., a biotechnology firm headquartered in Cambridge, Massachusetts, and Toronto, Ontario, focuses on developing antibody treatments for neurodegenerative disorders like Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA). Recently, the company unveiled preclinical data at the 4th International Conference on Cognitive & Behavioral Neurosciences (ICBN) in Lisbon, Portugal, underscoring the potential efficacy of its leading product candidate, PMN310, in treating AD.

Research has identified that the most harmful form of amyloid-beta (Aß) in Alzheimer's disease is not the insoluble fibrils and monomers but the soluble toxic oligomers. The therapeutic efficiency of antibodies could be significantly improved by targeting these toxic amyloid-beta oligomers (AßO) without engaging with the non-toxic species. PMN310 is designed as a next-generation antibody with enhanced selectivity for these toxic oligomers, potentially offering more effective treatment options.

Dr. Johanne Kaplan, ProMIS Neurosciences' Chief Development Officer, emphasized the importance of these findings, stating that PMN310 shows increased selectivity for toxic oligomers. This selectivity could reduce the risk of amyloid-related imaging abnormalities (ARIA), a common dose-limiting toxicity linked to plaque-binding antibodies. The company’s data additionally reveals that PMN310 does not bind to amyloid-beta plaque or vascular deposits, a unique characteristic among Aß-directed antibodies.

The preclinical studies evaluated the binding affinity of PMN310 and other Aß-targeting antibodies to a toxic oligomer-enriched fraction of brain extract from AD patients using surface plasmon resonance, both with and without monomer competition. PMN310 exhibited minimal interaction with monomers and maintained its binding capability to toxic oligomers even amidst high levels of monomer competition. Immunohistochemistry further indicated that PMN310 did not bind to amyloid-beta plaque or vascular deposits, suggesting a potentially improved safety and efficacy profile compared to other Aß-directed antibodies.

In July 2024, ProMIS reported favorable topline data from the initial four cohorts in its first-in-human Phase 1a clinical trial of PMN310, meeting key objectives for tolerability, safety, and pharmacokinetics. The firm plans to present topline results from all five cohorts soon and intends to initiate a Phase 1b study in the last quarter of 2024.

PMN310 is a humanized monoclonal antibody developed to specifically target soluble amyloid beta oligomers (AβOs), which are believed to be the most toxic and harmful form of amyloid-beta. These soluble AβOs are known to bind to neurons, inhibiting synaptic function and instigating neurodegeneration. By selectively attacking these toxic AβOs, PMN310 aims to tackle what is increasingly recognized as a primary cause of neurodegeneration in Alzheimer’s disease.

ProMIS Neurosciences Inc. continues to make strides in developing antibody treatments aimed at toxic misfolded proteins in neurodegenerative diseases such as AD, ALS, and MSA. The company employs a proprietary discovery platform, ProMIS™ and Collective Coordinates, to identify novel targets known as Disease Specific Epitopes on the molecular surface of misfolded proteins. Through this innovative approach, ProMIS is working on generating novel antibody therapeutics to address these debilitating diseases.

ProMIS Neurosciences operates offices in Cambridge, Massachusetts, and Toronto, Ontario.