Alzheimer Agent PMN310 Shows No ARIA-E in Six-Month Interim Analysis of Phase 1b AD Trial

In recent news, ProMIS Neurosciences reported positive six-month blinded interim safety and biomarker data from PRECISE-AD, the phase 1b trial of PMN310, an antibody designed to selectively target toxic amyloid-beta oligomers in patients with Alzheimer disease (AD).¹ Overall, no cases of ARIA-E were observed across all genotypes, including APOE4 homozygotes, and unblinded topline 12-month results are expected in the first quarter of 2027.¹

Interim safety and biomarker findings

In the blinded interim analysis of 136 patients with AD, PMN310 showed a favorable safety profile across all genotypes, including a subgroup that was 61% APOE4 carriers, of whom 11% were homozygotes. In addition, no ARIA-E was reported at the data cutoff, and total ARIA was 4.4%, consisting entirely of mild, asymptomatic ARIA-H (microhemorrhages); there were no treatment-related serious adverse events and no drug-related discontinuations.¹

On a blinded basis, 68.5% of patients showed a decline from baseline in plasma pTau217 and 62.5% showed a decline in CSF MTBR-tau243, both against an expected increase under natural disease progression. The company characterized this as potentially reflective of the trial's 3:1 active-to-placebo randomization and consistent with target engagement, while cautioning that these are blinded observations not yet tied to specific treatment arms, and that biomarker trends may not ultimately predict clinical effects.¹

"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," Neil Warma, chief executive officer of ProMIS Neurosciences, said in a statement.¹

Will Mantyh, MD, a behavioral neurologist at the University of Minnesota, added, "In real-world practice, ARIA risk is the central prescribing barrier... A profile with low incidence of total ARIA, including no ARIA-E, would be a game-changer. Just as importantly, plasma pTau217 and CSF MTBR-tau243 are among the most informative fluid biomarkers we have for tracking Alzheimer's biology; seeing early, coherent movement in both is highly encouraging before a definitive readout."¹

Trial design

For context, PRECISE-AD (NCT06750432) is a randomized, double-blind, placebo-controlled study evaluating multiple ascending intravenous doses of PMN310 (5, 10, and 20 mg/kg) in patients with mild cognitive impairment due to AD or mild AD, with treatment continuing over 12 months.¹

The trial has since completed enrollment of 144 participants across the three dosing cohorts; when it launched in January 2025, it had targeted 100 patients across 22 US sites using a fixed-dose 3:1 randomization scheme (350, 700, and 1400 mg), indicating the protocol was later revised to the weight-based dosing and larger enrollment reflected in current reporting.²

Background: PMN310 and prior phase 1a data

PMN310, a humanized IgG1 monoclonal antibody, is designed to selectively bind toxic amyloid-beta oligomers, believed to be among the earliest and most damaging drivers of AD pathology, while avoiding plaques and vascular deposits, a mechanism intended to decouple potential efficacy from ARIA risk. In addition, the FDA granted PMN310 Fast Track designation in July 2025.¹

The phase 1a trial in healthy volunteers (NCT06105528) enrolled 40 individuals aged 18-65 across 2 US sites and evaluated 4 single-ascending dose cohorts (2.5, 5, 10, and 20 mg/kg). Treatment was well tolerated, and CSF levels of PMN310 showed dose-proportional, target-engaging concentrations at days 3 and 29, with the lowest dose achieving greater than 100-fold molar excess over expected oligomer levels in CSF; the observed half-life of approximately 25 days supported a once-monthly dosing schedule.³

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. News release. ProMIS Neurosciences Inc. July 28, 2026. Accessed July 29, 2026. https://www.promisneurosciences.com/news-media/press-releases/detail/271/promis-neurosciences-reports-positive-blinded-six-month
2. ProMIS Neurosciences Initiates Phase 1b Clinical Trial (PRECISE-AD) in Alzheimer's Disease. News release. ProMIS Neurosciences Inc. January 10, 2025. Accessed July 29, 2026. https://www.globenewswire.com/news-release/2025/01/10/3007552/0/en/ProMIS-Neurosciences-Initiates-Phase-1b-Clinical-Trial-PRECISE-AD-in-Alzheimer-s-Disease.html
3. ProMIS Neurosciences Reports Positive Top-Line Data from its Phase 1a Alzheimer's Trial. News release. ProMIS Neurosciences Inc. July 26, 2024. Accessed July 29, 2026. https://www.globenewswire.com/news-release/2024/07/26/2919566/0/en/ProMIS-Neurosciences-Reports-Positive-Top-Line-Data-from-its-Phase-1a-Alzheimer-s-Trial.html