ProMIS Neurosciences (Nasdaq: PMN) reported blinded six-month interim safety and biomarker data from its Phase Ib Alzheimer's disease trial, with no cases of amyloid-related imaging abnormalities-edema (ARIA-E) observed across any genotype, including APOE4 homozygotes—a population at highest risk of treatment-related ARIA with currently approved anti-amyloid therapies.
The PRECISE-AD trial is evaluating PMN310, a humanized IgG1 monoclonal antibody that, unlike plaque-binding antibodies, is designed to bind soluble amyloid-β oligomers, which are thought to be among the most neurotoxic forms of amyloid while potentially avoiding interactions with vascular amyloid associated with ARIA.
In the blinded interim analysis of 136 patients, total ARIA was reported at 4.4%, consisting entirely of mild, asymptomatic ARIA-H microhemorrhages, with no treatment-related serious adverse events and no drug-related discontinuations. The trial enrolled 144 participants across three intravenous dosing cohorts of 5, 10, and 20 mg/kg, with a 3:1 active-to-placebo randomization, and remains blinded.
On biomarkers, 68.5% of patients showed a decline from baseline in plasma pTau217 and 62.5% showed a decline in CSF MTBR-tau243, against expected increases based on natural-history trajectories. The company noted these directional trends are consistent with the trial's randomization pattern and potential target engagement, but explicitly stated the observations are not a determination of efficacy and may not ultimately reflect clinical effects. Treatment allocations remain unknown. Unblinded 12-month topline data, including efficacy endpoints, are expected in Q1 2027.