ProMIS Reports Positive Interim Phase 1b Results for Alzheimer's Drug Candidate PMN310

Early Clinical Data Shows Encouraging Safety Profile

ProMIS Neurosciences Inc., a clinical-stage biopharmaceutical company, has announced positive six-month blinded interim results from its Phase 1b PRECISE-AD clinical trial evaluating PMN310 in patients with mild cognitive impairment due to Alzheimer's disease and patients with mild Alzheimer's disease.

According to the company, the interim analysis showed a favorable safety profile along with early changes in important disease-related biomarkers. The study remains ongoing, and topline 12-month results are expected during the first quarter of 2027.

Study Evaluated 136 Patients

The interim analysis included data from 136 patients participating in the PRECISE-AD trial.

The study is investigating PMN310, an investigational monoclonal antibody designed to treat Alzheimer's disease by targeting toxic amyloid-beta oligomers while avoiding amyloid plaques.

Researchers evaluated safety, tolerability, and biomarker changes during the first six months of treatment.

No Cases of ARIA-E Reported

One of the most important findings from the interim analysis was the absence of amyloid-related imaging abnormalities-edema (ARIA-E).

ARIA-E is a known safety concern with several currently approved amyloid-targeting Alzheimer's therapies because it involves swelling in the brain that may require additional monitoring or treatment.

As of the interim data cutoff, no cases of ARIA-E were observed.

The company also reported that total amyloid-related imaging abnormalities (ARIA) occurred in 4.4% of patients. All reported cases involved mild and asymptomatic amyloid-related imaging abnormalities-microhemorrhages (ARIA-H).

Researchers also reported:

• No treatment-related serious adverse events
• No drug-related treatment discontinuations

These findings suggest that PMN310 continues to demonstrate a favorable safety profile during the ongoing study.

Safety Maintained in High-Risk Genetic Groups

The favorable safety results were also seen among patients carrying the APOE4 gene variant.

Approximately 61% of study participants were APOE4 carriers, including 11% who carried two copies of the gene, a group generally considered to have a higher risk of Alzheimer's disease progression and treatment-related complications.

Even within this higher-risk population, researchers reported no cases of ARIA-E.

Biomarker Changes Suggest Drug Activity

The company also observed encouraging early changes in several Alzheimer's disease biomarkers.

Although the study remains blinded and researchers do not yet know which patients received PMN310 or placebo, many participants showed reductions in biomarkers that are normally expected to increase as Alzheimer's disease progresses.

Among the patients evaluated:

• 68.5% showed a decline in plasma pTau217 from baseline.
• 62.5% showed a decline in cerebrospinal fluid MTBR-tau243.

These biomarkers are widely used to monitor disease activity in Alzheimer's disease.

The company noted that these observations may reflect the study's 3:1 randomization in favor of active treatment. However, because the trial remains blinded, these biomarker trends cannot yet be interpreted as proof of treatment effectiveness.

PMN310 Uses a Different Treatment Approach

PMN310 has been designed to selectively bind toxic amyloid-beta oligomers rather than amyloid plaques.

Researchers believe these toxic oligomers are among the earliest drivers of Alzheimer's disease.

Unlike plaque-targeting therapies, PMN310 aims to avoid binding to amyloid plaques and blood vessel deposits, which may reduce the risk of ARIA while still targeting disease-related proteins.

This selective mechanism is intended to separate potential clinical benefit from the safety concerns seen with some existing Alzheimer's therapies.

Company Looks Ahead to 12-Month Results

ProMIS Chief Executive Officer Neil Warma said the interim findings support the company's strategy of targeting toxic amyloid-beta oligomers while minimizing the risk of ARIA.

He said the absence of ARIA-E, the favorable overall safety profile, and the early biomarker trends are consistent with expectations based on previous research.

The company now plans to complete the ongoing trial and expects topline unblinded results during the first quarter of 2027, including efficacy data.

Experts See Potential Benefit

Dr. Will Mantyh, a behavioral neurologist at the University of Minnesota, said ARIA remains one of the biggest challenges when prescribing currently available amyloid-targeting therapies.

He noted that clinicians, patients, and healthcare systems often need additional monitoring because of the risk of brain swelling and related complications.

According to Dr. Mantyh, a treatment showing a low incidence of ARIA and no cases of ARIA-E could represent an important advancement.

He also highlighted that plasma pTau217 and cerebrospinal fluid MTBR-tau243 are among the most useful biomarkers currently available for monitoring Alzheimer's disease progression, making the observed early biomarker changes encouraging ahead of the final study results.

About the PRECISE-AD Clinical Trial

PRECISE-AD is a randomized, double-blind, placebo-controlled Phase 1b clinical study evaluating PMN310 in patients with mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease.

The study has enrolled 144 participants across three dose groups:

• 5 mg/kg
• 10 mg/kg
• 20 mg/kg

Participants receive intravenous PMN310 treatment for 12 months.

Researchers are evaluating safety, tolerability, pharmacokinetics, disease biomarkers, and clinical outcomes throughout the study.

Fast Track Status Supports Development

PMN310 received Fast Track Designation from the US Food and Drug Administration (FDA) in July 2025.

The designation is intended to help speed the development and review of therapies that address serious medical conditions with significant unmet needs.

The ongoing PRECISE-AD trial follows encouraging findings from an earlier Phase 1a study conducted in healthy volunteers.

About ProMIS Neurosciences

ProMIS Neurosciences is a clinical-stage biotechnology company focused on developing therapeutic antibodies and vaccines that selectively target toxic protein oligomers involved in neurodegenerative diseases.

The company's research is centered on developing treatments for Alzheimer's disease and other disorders caused by misfolded proteins using highly selective antibody technologies.