Phase 1b Trial of Oligomer-Targeting Agent PMN310 for Alzheimer Disease Gets Underway

ProMIS Neurosciences Inc. announced the initiation of its phase 1b clinical trial, PRECISE-AD, to evaluate PMN310, a monoclonal antibody, as a treatment for Alzheimer disease (AD).

The trial will assess the safety, tolerability, and pharmacokinetics of PMN310 in people with mild cognitive impairment due to AD (stage 3) or early-stage AD (stage 4). Key biomarkers and clinical efficacy measures will also be evaluated, according to a January 10, 2025, press release.1

PMN310 is a humanized IgG1 antibody designed to selectively target toxic amyloid-beta oligomers (AβO), which are thought to be a key factor in AD pathology, without binding to amyloid plaques. This mechanism is intended to reduce the risk of amyloid-related imaging abnormalities (ARIA), a known side effect associated with some existing AD treatments.1 Results from a phase 1a study in healthy volunteers demonstrated a favorable safety profile and robust cerebrospinal fluid drug concentrations, supporting further investigation in patients with AD.2

“Current AD treatments offer only modest efficacy, often accompanied by significant side effect challenges such as ARIA, leaving a substantial unmet need for new options,” Neil Warma, CEO of ProMIS Neurosciences, said in the press release.1 “We believe PMN310 has the potential to deliver on this need through its selective targeting mechanism.”

The randomized, double-blind, placebo-controlled study will enroll approximately 100 patients across 22 active clinical sites in the US. Participants will receive monthly intravenous doses of PMN310 at 1 of 3 levels (5, 10, or 20 mg/kg) or a placebo over a 12-month period. Regular assessments will include MRI scans to monitor for ARIA. Blood and cerebrospinal fluid samples will be collected to track pharmacodynamic markers and evidence of target engagement.1

“Monoclonal antibodies targeting toxic amyloid-beta species are the first treatments that have shown disease modifying capacity for Alzheimer's disease. It is often preferable to have multiple therapeutics available as treatment options. Thus, PMN310 is exciting because of its novel targeting of amyloid oligomers, potentially offering another solution for physicians and their patients,” Cameron S. Olezene, MD, principal investigator at Flourish Research in Philadelphia, one of the first sites to become activated in the PRECISE-AD trial, said in the press release.1

The PRECISE-AD trial aims to generate comprehensive data to guide future development, including interim findings anticipated in the first half of 2026.1

References:

1. ProMIS Neurosciences initiates phase 1b clinical trial (PRECISE-AD) in Alzheimer’s disease. News release. ProMIS Neurosciences. January 10, 2025. Accessed January 13, 2025. https://www.promisneurosciences.com/news-media/press-releases/detail/236/promis-neurosciences-initiates-phase-1b-clinical-trial

2. ProMIS Neurosciences presents positive data from PMN310 phase1a clinical trial at the 17th Clinical Trials on Alzheimer’s Disease Conference. News release. ProMIS Neurosciences. October 30, 2024. Accessed January 13, 2025. https://www.promisneurosciences.com/investors/news-events/press-releases/detail/232/promis-neurosciences-presents-positive-data-from-pmn310