Dr. Gail Farfel reports

PROMIS SHOWCASES PRECLINICAL DATA AT THE ALZHEIMER'S ASSOCIATION INTERNATIONAL CONFERENCE 2023 ON COMPUTATIONALLY-DERIVED ANTIBODY AND VACCINE FROM ALZHEIMER'S PIPELINE

Promis Neurosciences Inc. has provided details of preclinical data further supporting the potential therapeutic advantage of its lead candidate for Alzheimer's disease (AD), PMN310, a humanized IgG1 antibody directed toward toxic amyloid-beta oligomers (AbetaO). Additionally, the company has detailed preclinical mouse studies that further characterize a computationally derived AD vaccine directed at AbetaO. Promis's proprietary algorithm identifies targets specific to a toxic protein species to avoid cross-reactivity with other forms of the same protein. The data were presented in posters on July 16, 2023, at the Alzheimer's Association International Conference (AAIC) 2023 in Amsterdam, Netherlands.

"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 Dr. Gail Farfel, PhD, chief executive officer of Promis Neurosciences. "The increasingly recognized benefit of targeting oligomers of Abeta underscores the potential advantage of our PMN310 antibody and AbetaO vaccine candidates. Both were generated using our proprietary computational modelling platform to identify epitopes restricted to misfolded, toxic AbO, thereby providing a highly selective AbetaO-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, MD

In preclinical studies, the binding selectivity of PMN310 was compared with that of other Abeta-directed antibodies using surface plasmon resonance. The results demonstrated that PMN310 was able to selectively bind to toxic AbetaO in AD brain extract and was less impacted by monomer competition than other Abeta-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 Abeta-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: Dr. Cashman, MD

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's vaccine candidate, consisting of an AbetaO 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 AbetaO 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 AbetaO 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 with chronic antibody treatment.

Both poster presentations are available on the posters and publications page of the company's website.

About Promis Neurosciences Inc.

Promis Neurosciences 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, Ont., and Cambridge, Mass.

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