Poster presentation of study highlighting oligomer selectivity of PMN310 compared to that of other amyloid-beta-directed antibodies
Dr. Johanne Kaplan, ProMIS Chief Development Officer delivered a poster presentation on July 31st entitled: “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 amyloid-beta (Aß) in Alzheimer’s disease (AD) consist of soluble toxic oligomers as opposed to insoluble fibrils (plaque) and monomers. The ability of a therapeutic antibody to target toxic Aß oligomers without being diverted by binding to competing non-toxic species is expected to result in greater efficacy.
The poster describes a study comparing ProMIS’ lead therapeutic candidate PMN310 to other Aß-directed antibodies for selectivity and ability to maintain interaction with toxic oligomers in the presence of competing Aß monomers. The binding of multiple Aß-directed antibodies to synthetic oligomers with and without pre-exposure to competing monomers, was evaluated by surface plasmon resonance (SPR). Binding of the antibodies to a toxic oligomer-enriched low molecular fraction of brain extract from Alzheimer’s disease (AD) patients was similarly evaluated by SPR, with and without monomer competition.
Results of this study showed that PMN310 displayed little or no interaction with monomers and was among the least impacted by excess monomer competition in binding to synthetic oligomers or to naturally occurring toxic oligomers in AD brain extract. This characteristic was shared by other Aß antibodies that have shown positive clinical outcomes, such as donanemab, lecanemab and aducanumab. In contrast, non-selective antibodies that failed in pivotal trials, such as crenezumab and solanezumab, were strongly inhibited by monomer competition.
In conclusion, PMN310 distinguished itself from other Aß-directed antibodies by its enhanced selectivity for toxic oligomers (negligible binding to monomers and plaque) along with its ability to withstand competition by abundant monomers. Additionally, the avoidance of interaction with plaque and vascular deposits by PMN310 could potentially reduce the risk of brain swelling associated with plaque-binding antibodies (amyloid-related imaging abnormality with edema, ARIA-E).
The narrated poster presentation will be available on the ProMIS website www.promisneurosciences.com after the AAIC® closes on August 4, 2022.
ProMIS Neurosciences’ lead therapeutic candidate, PMN310, is a monoclonal antibody for Alzheimer’s disease created with a novel, proprietary method for generating and developing antibodies that can uniquely and precisely target toxic forms of otherwise normal proteins. PMN310 selectively targets the toxic oligomeric species of amyloid-beta (Aß), a root cause of Alzheimer’s disease. Preclinical studies have shown that PMN310 demonstrates a high degree of selectivity and protective activity against toxic oligomers.
About ProMIS Neurosciences
ProMIS Neurosciences Inc. is a development stage biotechnology company focused on generating and developing antibody therapeutics selectively targeting toxic oligomers implicated in the development and progression of neurodegenerative diseases, in particular Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). The Company’s proprietary target discovery engine is based on the use of two complementary techniques. The Company applies its thermodynamic, computational discovery platforms – ProMIS™ and Collective Coordinates – to predict novel targets known as Disease Specific Epitopes on the molecular surface of misfolded proteins. Using this unique approach, the Company is developing novel antibody therapeutics for AD, ALS and PD. ProMIS is headquartered in Toronto, Ontario, with offices in Cambridge, Massachusetts. ProMIS is listed on Nasdaq and the Toronto Stock Exchange under the symbol PMN.
For Investor Relations please contact:
Alpine Equity Advisors
Nicholas Rigopulos, President
Tel. 617 901-0785
The TSX has not reviewed and does not accept responsibility for the adequacy or accuracy of this release. This information release contains certain forward-looking information. Such information involves known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from those implied by statements herein, and therefore these statements should not be read as guarantees of future performance or results. All forward-looking statements are based on the Company’s current beliefs as well as assumptions made by and information currently available to it as well as other factors. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Due to risks and uncertainties, including the risks and uncertainties identified by the Company in its public securities filings, actual events may differ materially from current expectations. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.