ProMIS Neurosciences has reported six-month interim safety and biomarker data from the Phase 1b PRECISE-AD trial of PMN310 in patients with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease, with no cases of amyloid-related imaging abnormalities-edema (ARIA-E) observed across all genotypes.

The blinded interim analysis included 136 patients and found a favourable safety profile, including in patients carrying the APOE4 gene variant, which is associated with an increased risk of ARIA in some amyloid-directed Alzheimer’s therapies.

The company said 61% of patients in the trial were APOE4 carriers, including 11% who were APOE4 homozygotes. No cases of ARIA-E were reported at the six-month data cutoff, while total ARIA was 4.4%, consisting only of mild, asymptomatic amyloid-related imaging abnormalities-microhemorrhages (ARIA-H).

No treatment-related serious adverse events or drug-related discontinuations were reported in the interim analysis.

The findings are relevant as researchers continue to develop treatments that target the underlying biology of Alzheimer’s disease while seeking to reduce the safety risks associated with existing amyloid-directed approaches.

PMN310 targets toxic amyloid-beta oligomers

PMN310 is an investigational therapy designed to selectively bind toxic amyloid-beta oligomers while avoiding amyloid plaques. ProMIS believes this approach could allow the drug to target disease-driving forms of amyloid while potentially reducing the risk of ARIA.

The company said the blinded interim analysis also showed early movement in disease-relevant biomarkers. A majority of patients showed reductions from baseline in plasma pTau217 and cerebrospinal fluid (CSF) MTBR-tau243, biomarkers associated with Alzheimer’s disease pathology.

According to the interim analysis, 68.5% of patients had a decline from baseline in plasma pTau217, while 62.5% had a decline in CSF MTBR-tau243.

However, the trial remains blinded, meaning researchers do not yet know which patients received PMN310 and which received placebo. The company said the biomarker observations are therefore not a determination of efficacy and may not ultimately translate into clinical benefit.

The company also noted that the observed biomarker trends could potentially reflect the trial’s 3:1 active-to-placebo randomisation, highlighting the need for further data before conclusions can be drawn about PMN310’s effectiveness.

Alzheimer’s safety data to be followed by efficacy results

The interim findings provide an early look at the safety and biological activity of PMN310, but the next major milestone will be the planned 12-month topline readout, which is expected in the first quarter of 2027 and will include efficacy data.

Neil Warma, chief executive officer of ProMIS Neurosciences, said: “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.”

Warma added that the absence of ARIA-E, the overall safety profile and early biomarker movement were consistent with the company’s expectations based on earlier studies.

The potential safety profile of PMN310 was also highlighted by Will Mantyh, a behavioural neurologist at the University of Minnesota, who said: “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.”

Mantyh added that a low incidence of total ARIA, alongside movement in plasma pTau217 and CSF MTBR-tau243, would be encouraging ahead of a definitive readout.

The PRECISE-AD trial remains ongoing and blinded. ProMIS expects to report 12-month topline data in Q1 2027, providing a clearer assessment of whether the early biomarker findings translate into clinical efficacy.