Positive Safety and Biomarker Phase 1b Results for PMN310 Mild Cognitive Impairment and Alzheimer Disease

ProMIS Neurosciences reported positive 6-month interim safety and biomarker data for PMN310, a monoclonal antibody targeting amyloid-beta oligomers designed to treat mild cognitive impairment due to Alzheimer disease and mild Alzheimer disease.¹ The drug was shown to have a favorable safety profile across genotypes, with no cases of amyloid-related imaging abnormalities-edema (ARIA-E) reported.² Positive observations of consistent movement in disease-relevant biomarkers may potentially reflect randomization of treatment, investigators noted.

“These interim data reinforce our central thesis: by selectively targeting toxic oligomers, PMN310 has the potential to deliver the benefits of amyloid-directed therapy without the ARIA burden that has constrained this class of drugs,” said Neil Warma, chief executive officer of ProMIS Neurosciences.¹ “The absence of ARIA-E, an overall favorable safety profile, and early biomarker movement together align with our expectations based on our prior studies. We look forward to our 12-month topline readout in the first quarter of 2027,” he added.

The PRECISE-AD phase 1b trial blinded interim results are based on 136 patients with mild cognitive impairment due to Alzheimer disease or general mild Alzheimer disease. Previous phase 1a data in healthy patients showed encouraging data which supported the phase 1b trial. PRECISE-AD is a randomized, double-blind, placebo-controlled study evaluating the pharmacokinetics, safety, and tolerability of multiple ascending doses of intravenous PMN310. Doses studied include 5, 10, and 20 mg/kg. The full study includes 144 patients across 3 dosing cohorts who will receive treatment for 12 months. Patients carrying APOE4 were included in the trial and the interim analysis.

Highlights from phase1b interim analysis include a favorable safety profile across all genotypes, no serious treatment-related adverse events, and no drug-related discontinuations. No ARIA-E was observed, even in high-risk APOE4 carriers—11% of whom were homozygotes. Total ARIA prevalence was 4.4% with all occurrences being mild, asymptomatic, and consisting only of ARIA microhemorrhage. In terms of biomarkers, a majority of patients showed reductions in disease-relevant biomarkers compared with expected increase in natural-history trajectories: 68.5% had a decline in plasma pTau217 and 62.5% had a decline in CSF MTBR-tau243. Investigators noted these percentages are consistent with a potential beneficial drug effect and potentially reflective of the trial’s 3:1 treatment vs placebo randomization, but do not confirm efficacy at this time.

Will Mantyh, MD, a behavioral neurologist at the University of Minnesota, commented “In real-world practice, ARIA risk is the central prescribing barrier: clinicians, patients, and health systems must contend with the issues of safety monitoring, identification, and sometimes emergent neurological treatment of ARIA. A profile with low incidence of total ARIA, including no ARIA-E, would be a game-changer.” He highlighted that “Just as importantly, plasma pTau217 and CSF MTBR-tau243 are among the most informative fluid biomarkers we have for tracking Alzheimer biology; seeing early, coherent movement in both is highly encouraging before a definitive readout.”

PMN310 is a humanized IgG1 monoclonal antibody which selectively targets toxic oligomers of amyloid-beta while avoiding binding to amyloid plaques and vascular deposits. With this selectivity, the drug potentially can reduce or eliminate risk of ARIA, including edema and microhemorrhage. The monoclonal antibody was granted Fast Track Designation by the US Food and Drug Administration in July 2025.

Unblinded 12-month topline data, including efficacy, are expected in the beginning of 2027.

References

1. ProMIS Neurosciences reports positive blinded six-month interim safety and biomarker data for PMN310 in the PRECISE-AD phase 1b Alzheimer’s disease trial. Press release. July 28, 2026. Accessed July 28, 2026. https://www.biospace.com/press-releases/promis-neurosciences-reports-positive-blinded-six-month-interim-safety-and-biomarker-data-for-pmn310-in-the-precise-ad-phase-1b-alzheimers-disease-trial

2. PMN310 in patients with early Alzheimer’s disease (PRECISE-AD). ClinicalTrials.gov. July 13, 2026. Accessed July 28, 2026. https://clinicaltrials.gov/study/NCT06750432