ProMIS Neurosciences has announced the first human evidence of dose-dependent amyloid-beta oligomer (AβO) reduction by its lead Alzheimer’s drug candidate, PMN310, in data presented at the 2026 Alzheimer’s Association International Conference (AAIC) in Cambridge, Massachusetts.

The findings, derived from analysis of samples collected during the company’s Phase 1a trial in healthy volunteers (NCT06105528), demonstrated that individuals receiving PMN310 exhibited a dose-dependent reduction in detectable AβO in cerebrospinal fluid (CSF) at both three and 29 days after dosing. While healthy individuals carry lower oligomer burdens than Alzheimer’s patients, amyloid-beta oligomers are detectable in CSF even in cognitively normal adults, making this a meaningful measure of target engagement.

“This represents one of the first quantitative demonstrations of treatment-related oligomer reduction in humans,” the company stated.

Neil Warma, Chief Executive Officer of ProMIS Neurosciences, highlighted the significance of the findings: “These data represent an important milestone for PMN310 and offer evidence supporting our precision medicine approach in treating Alzheimer’s disease. Using CSF samples from our Phase Ia study, subjects receiving PMN310 showed a clear dose-dependent reduction in oligomer particles, which, we believe, represents direct evidence that PMN310 was able to reach the brain and engage its intended target.”

Warma also acknowledged the contribution of the company’s partner, attyloid, for their role in assay development, noting that ProMIS intends to deploy this assay in its ongoing PRECISE-AD Phase 1b trial to directly measure oligomer burden in Alzheimer’s patients before and after treatment.

Differentiated Mechanism Targets Toxic Oligomers While Sparing Plaque

Dr. Johanne Kaplan, Chief Development Officer of ProMIS Neurosciences, provided context on the therapeutic rationale behind PMN310’s selective approach. “A large body of evidence in Alzheimer’s disease research indicates that disease pathogenesis is not directly driven by plaque burden, but rather by soluble toxic amyloid-beta oligomers. Selectively targeting oligomers while avoiding plaque could have a meaningful impact on both the efficacy and safety of treatment, reducing off-target binding that limits effective dosing and potentially limiting the ARIA side effects associated with plaque-binding antibodies.”

Kaplan added that the data presented provide pharmacodynamic evidence supportive of PMN310’s differentiated mechanism of action.

Key Results Presented at AAIC 2026

The poster presentation detailed several key findings:

Oligomer Reduction: Placebo-treated healthy volunteers (N=40) in the Phase 1a trial exhibited low levels of AβO in CSF. PMN310 administration resulted in a dose-dependent reduction in detectable AβO particles in CSF.

Strict Oligomer Selectivity: PMN310 demonstrated strong binding to AβO with no interaction with monomers by surface plasmon resonance (SPR), and no detectable reactivity with plaques or vascular deposits of Aβ in Alzheimer’s disease brain tissue sections, representing the potential for a differentiated clinical profile.

Favorable Pharmacokinetics and Tolerability: PMN310 was generally well-tolerated, with CSF concentrations linearly dose-dependent, reaching 100–600 times the estimated molar concentration of AβO, and a CSF half-life of approximately 27 days.

Preclinical Memory Preservation: In a transgenic Alzheimer’s disease mouse model, PMN310 preserved memory and learning performance in the Morris Water Maze task.

The assay used to measure amyloid-beta oligomers in CSF was surface-based fluorescence intensity distribution analysis (sFIDA), developed by attyloid GmbH, which enables direct quantification of oligomer particles with unprecedented sensitivity. While the assay is currently exploratory, it provides pharmacodynamic evidence of target engagement by PMN310.

PMN310, ProMIS’ lead product candidate for the treatment of Alzheimer’s disease, is a humanized IgG1 monoclonal antibody designed to selectively target only the toxic oligomers of amyloid-beta, believed to be among the earliest and most damaging drivers of Alzheimer’s disease, while avoiding binding to amyloid plaques and vascular deposits. This selectivity may reduce or eliminate the risk of amyloid-related imaging abnormalities (ARIA), including brain swelling (ARIA-E) and microhemorrhages (ARIA-H), which are commonly associated with plaque-binding antibodies.

PMN310 was granted Fast Track Designation by the US Food and Drug Administration in July 2025. Based on encouraging results from the Phase 1a trial in healthy volunteers, ProMIS initiated the PRECISE-AD Phase 1b trial to evaluate PMN310 in patients with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease.

PRECISE-AD (NCT06750432) is a randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and pharmacokinetics of multiple ascending doses (5, 10, and 20 mg/kg) of intravenous PMN310. The study has completed enrollment of 144 participants across the three dosing cohorts who are being treated for twelve months.

ProMIS expects to share blinded six-month interim data from the PRECISE-AD Phase 1b trial in the coming weeks. The interim analysis will focus on blinded aggregate safety data and overall trends in selected biomarkers across study participants. Top-line unblinded results are expected in early Q1 2027.