FDA Clears IND for Phase 1 Study of Monoclonal Antibody PMN310 for Alzheimer Disease

Gail Farfel, PhD

According to an announcement from ProMis Neurosciences, the FDA has accepted its investigational new drug (IND) application for PMN310, an investigational monoclonal antibody in development for the treatment of Alzheimer disease (AD). The company is expected to initiate a phase 1a clinical study assessing the pharmacokinetics, safety, and tolerability of multiple doses of PMN310 in healthy volunteers.¹

"Receiving IND clearance for PMN310 marks an important corporate milestone as we continue towards our goal of delivering next-generation therapy to patients with Alzheimer’s disease who have limited options to slow cognitive decline," Gail Farfel, PhD, chief executive officer, ProMis Neurosciences, said in a statement.¹ "Our preclinical data demonstrated PMN310’s greater selective binding to toxic oligomers compared to other Aβ-directed antibodies, which we believe supports the potential clinical profile of PMN310. We look forward to advancing PMN310 into clinical development and sharing what we learn from this innovative work."

PMN310 is designed to selectively target the toxic oligomers of amyloid-ß, with a possibly more favorable clinical safety and efficacy profile over other amyloid-directed therapeutics currently in development. The agent does not bind monomers, plaque, or vascular deposits, potentially lowering the risk for amyloid-related imaging abnormalities (ARIA), an issue seen in AD drug development. Additionally, doses of PMN310 may not be limited by off-target binding or adverse events.

In March 2022, ProMis announced findings from an animal model study of AD showing significant cognitive benefits with treatment of PMN310.² Using a transgenic model, treatment with the agent resulted in preserved memory, to the extent that treated mice were indistinguishable from non-transgenic control mice. The positive result built on earlier in vivo data for PMN310 that was published in mid-2019.

Additional preclinical data has been presented at several scientific conferences, including the 2022 Alzheimer’s Association International Conference (AAIC) and the 2023 American Academy of Neurology (AAN) Annual Meeting. At AAIC 2022, a group of investigators presented an analysis comparing the ability of PMN310 to target toxic oligomers with other amyloid-ß (Aß) antibodies in the presence of competing monomers. In the results, PMN310 showed selective binding to toxic oligomers and, when compared with other Aß antibodies, was the least impacted by excess monomer competition in binding to synthetic oligomers or naturally occurring toxic oligomers in AD brain extract.³

Similar findings were reported at the most recent AAN Annual Meeting. Presented by Johanne Kaplan, PhD, chief development officer, ProMIS Neurosciences, data on PMN310 showed no detectable plaque staining, which helps avoid ARIA-edema, whereas other compared antiamyloid therapies such as aducanumab (Aduhelm; Biogen), donanemab (Eli Lilly), lecanemab (Leqembi; Eisai), and gantenerumab (Eli Lilly) have shown ARIA-E rates of around 35%, 30%, 15%, and 25%, respectively.⁴

REFERENCES
1. ProMIS Neurosciences announces FDA clearance of investigational new drug (IND) application for PMN310 in Alzheimer’s Disease. News release. ProMIS Neurosciences. May 8, 2023. Accessed May 8, 2023. https://www.biospace.com/article/releases/promis-neurosciences-announces-fda-clearance-of-investigational-new-drug-ind-application-for-pmn310-in-alzheimer-s-disease/
2. ProMIS Neurosciences’ PMN310 antibody demonstrates significant cognitive benefit in a mouse model of Alzheimer’s disease. March 2, 2022. Accessed May 8, 2023. https://www.biospace.com/article/releases/promis-neurosciences-pmn310-antibody-demonstrates-significant-cognitive-benefit-in-a-mouse-model-of-alzheimer-s-disease/
3. Gibbs E, Coutts J, Roman A, et al. Distinguishing between amyloid-beta-directed antibodies: ability of PMN310 to target toxic oligomers despite competing species. Presented at: AAIC 2022; Poster 67371
4. Kaplan J. Protection against toxic amyloid-beta oligomers by PMN310, a monoclonal antibody rationally designed for greater therapeutic potency in Alzheimer’s disease. Presented at: 2023 AAN Annual Meeting; April 22-27; Boston, MA. Poster 4597