• New findings highlight that PMN310 was able to target toxic amyloid-beta oligomers more selectively than other amyloid-beta-directed antibodies which were generated using synthetic oligomers
• Rationally designed vaccine candidate for prevention of Alzheimer’s disease showed robust and sustained antibody response focused on pathogenic amyloid-beta oligomers
“We are excited about the new data presented at the AAIC conference on mechanisms and monitoring of Alzheimer’s disease and emerging treatment options which we believe may improve the lives of patients and their families,” said Gail Farfel, Ph.D., Chief Executive Officer of ProMIS Neurosciences. “The increasingly recognized benefit of targeting oligomers of Aβ underscores the potential advantage of our PMN310 antibody and AβO vaccine candidates. Both were generated using our proprietary computational modeling platform to identify epitopes restricted to misfolded, toxic AO thereby providing a highly selective AβO-targeted response for potentially greater clinical activity and improved safety profile compared to less selective approaches. Furthermore, we are far along in our preparations to move PMN310 into clinical development with an informative trial design to evaluate its potential as a treatment for Alzheimer’s disease.”
In May 2023, ProMIS received clearance from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) application for PMN310 for the treatment of AD. The Company plans to initiate a Phase 1a clinical trial designed to evaluate the pharmacokinetics, safety and tolerability of a range of PMN310 doses in healthy adult volunteers as the first study in the PMN310 planned clinical development program.
Details of the poster presentation are as follows:
PMN310 for the Potential Treatment of Alzheimer’s Disease
Title: Selective targeting and protection against toxic amyloid-beta oligomers by PMN310, a monoclonal antibody rationally designed for greater therapeutic potency in Alzheimer’s disease
Session: Drug Development
Presenter: Neil Cashman, M.D.
In preclinical studies, the binding selectivity of PMN310 was compared to that of other Aβ-directed antibodies using surface plasmon resonance. The results demonstrated that PMN310 was able to selectively bind to toxic AβO in AD brain extract and was less impacted by monomer competition than other Aβ-directed antibodies except ACU193, which was equivalent to PMN310. Additionally, of all antibodies tested including biosimilars for ACU193 and PRX012, only PMN310 and solanezumab did not bind to plaque, potentially reducing the incidence of Aβ-related imaging abnormalities (ARIA) associated with plaque-binding antibodies. Additionally, PMN310 completely protected memory function as measured in two rodent models of AD, supporting evaluation of the candidate as a potential therapeutic option for the treatment.
Vaccine Candidate for Potential Prevention of Alzheimer’s Disease
Title: Rational design of a vaccine for Alzheimer’s disease using a computationally-derived conformational epitope to selectively target toxic amyloid-beta oligomers
Session: Drug Development
Presenter: Neil Cashman, M.D.
ProMIS presented a poster on its vaccine candidate being evaluated preclinically for the prevention of AD at AAIC. The findings were previously shared in an oral presentation at the 2023 at the American Academy of Neurology (AAN) Annual Meeting.
The preclinical evaluation of ProMIS’ vaccine candidate consisting of an AβO conformational B cell peptide epitope conjugated to a carrier protein to provide T cell help, elicited a robust and sustained antibody response with either alum or QS-21 as adjuvants approved for human use. The serum antibodies were selective for AβO with no detectable binding to monomers or plaque, potentially reducing the risk of ARIA. In addition, no potentially deleterious T helper responses to the conformational AβO peptide epitope were detected, potentially reducing the risk of meningoencephalitis. These results support ProMIS’s approach to designing a vaccine for AD prevention with the potential for sustained anti-disease activity and ease of use with fewer doses compared to chronic antibody treatment.
Both poster presentations are available on the Posters and Publications page of the Company’s website at http://www.promisneurosciences.com
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.
