PMN310 Alzheimer’s Antibody Shows Early Low-ARIA Signal, but Blinded Data Await Unblinding

Alzheimer’s antibodies designed to clear disease-causing proteins often require a trade-off between potential efficacy and brain imaging abnormalities. PMN310, developed by ProMIS Neurosciences, has now produced a preliminary signal: in a six-month interim analysis of a phase 1b clinical trial, there were no cases of ARIA-E involving brain edema, while the overall incidence of amyloid-related imaging abnormalities (ARIA) was 4.4%.

The analysis included 136 patients. All ARIA cases were mild, asymptomatic ARIA-H—microhemorrhages visible on imaging. The company also said that no treatment-related serious adverse events or drug-related trial discontinuations had been identified. Among the participants, 61% carried an APOE4 genetic variant and 11% were APOE4 homozygotes; patients in these groups are generally considered to face a higher risk of ARIA when treated with amyloid antibodies.

But the most important limitation at present is contained in the phrase “blinded pooled analysis.” Researchers have not yet disclosed which patients received PMN310 and which received placebo, so the 4.4% figure is the combined rate for both groups. It cannot establish in which group the imaging abnormalities primarily occurred, much less demonstrate that PMN310 is safer than existing therapies. The sample size and six-month follow-up period are also insufficient to rule out rarer or later-emerging risks.

PMN310 is designed to selectively recognize soluble, toxic amyloid-beta oligomers while avoiding plaques and vascular deposits as much as possible. ProMIS argues that this binding approach may reduce the ARIA burden commonly seen with plaque-targeting antibodies. The absence of ARIA-E so far is consistent with this hypothesis, but it does not establish a causal relationship.

The interim data also showed biomarker changes: plasma pTau217 declined from baseline in 68.5% of patients, while cerebrospinal fluid MTBR-tau243 declined in 62.5%. These markers are associated with tau pathology in Alzheimer’s disease, but the figures likewise come from pooled results combining the treatment and placebo groups. Biomarker reductions do not necessarily indicate cognitive benefit, and the company explicitly stated that efficacy cannot currently be determined from these findings.

The PRECISE-AD trial enrolled a total of 144 patients with mild cognitive impairment or mild Alzheimer’s disease and is evaluating intravenous doses of 5, 10, and 20 milligrams per kilogram over a 12-month treatment period. The unblinded results expected in the first quarter of 2027 will be the critical test: only then may it become clear what ARIA risk is associated with each dose, whether the biomarker changes were driven by the drug, and whether those changes can translate into measurable clinical benefit.