ProMIS Neurosciences Inc. (TSX: PMN) (Nasdaq: PMN), a biotechnology company focused on the generation and development of antibody therapeutics targeting toxic misfolded proteins in neurodegenerative diseases such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA), today presented new in vitro preclinical data supporting the differentiation of PMN310 from other amyloid-beta (Aβ)-directed antibodies at the International Conference on Alzheimer’s and Parkinson’s Disease and Related Neurological Disorders (AD/PD 2023).
Antibody therapies that target Aβ in AD continue to generate interest with recent approvals and new potential treatments in development. A large body of evidence suggests that soluble toxic Aβ oligomers, rather than Aβ 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 Aβ in the brain. In preclinical studies, ProMIS Neurosciences’ lead candidate, PMN310, has demonstrated its ability to selectively target pathogenic Aβ oligomers without unproductive binding to non-toxic monomers or plaque.
“We believe these encouraging data help differentiate our lead therapeutic candidate, PMN310, from other Aβ-directed antibodies. As shown in our AD/PD poster, PMN310 selectively targeted toxic oligomers and avoided interaction with plaque and vascular deposits,” said Johanne Kaplan, Ph.D., Chief Development Officer of ProMIS Neurosciences. “We believe that these data support clinical development of PMN310, and we are excited to submit an IND application in the coming weeks as we advance our plans to bring a next-generation therapy to patients suffering with Alzheimer’s disease.” Dr. Kaplan will be interviewed by VJNeurology during the AD/PD meeting. Links will be posted to the Events page of the ProMIS website once available.
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 Aβ-directed antibodies (PMN310, donanemab, aducanumab, lecanemab, crenezumab, solanezumab, gantenerumab) 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 (aducanumab, lecanemab, donanemab) 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 Aβ-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 (amyloid-related imaging abnormalities) side effects associated with plaque-binding antibodies.
ProMIS Neurosciences Inc. is a development stage biotechnology company focused on generating and developing antibody therapeutics selectively targeting toxic misfolded proteins in neurodegenerative diseases such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA). The Company’s proprietary target discovery engine is based on the use of two complementary techniques. The Company applies its thermodynamic, computational discovery platform – 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 MSA. ProMIS has offices in Toronto, Ontario and Cambridge, Massachusetts. ProMIS is listed on Nasdaq and the Toronto Stock Exchange under the symbol PMN.