ProMIS Reports Positive Phase 1b PMN310 Interim Results in Alzheimer’s Disease

ProMIS Neurosciences has reported positive blinded six-month interim results from the ongoing Phase 1b PRECISE-AD trial evaluating PMN310 in patients with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease. Among 136 evaluated participants, investigators observed no cases of amyloid-related imaging abnormalities-edema (ARIA-E), including in patients carrying high-risk APOE4 variants. The interim analysis also showed early directional changes in Alzheimer’s disease biomarkers consistent with target engagement, although the study remains blinded and these findings do not establish clinical efficacy.

Oligomer-Selective Approach Targets Toxic Amyloid Without Plaque Binding

PMN310 is a humanized IgG1 monoclonal antibody that selectively binds soluble toxic amyloid-beta oligomers, which are believed to play a key role in the earliest stages of Alzheimer’s disease. Unlike currently approved anti-amyloid antibodies that bind amyloid plaques, PMN310 avoids plaque and vascular amyloid deposits, an approach intended to reduce the risk of amyloid-related imaging abnormalities (ARIA), particularly ARIA-E.

The U.S. Food and Drug Administration granted PMN310 Fast Track designation in July 2025.

ARIA remains one of the principal safety challenges associated with approved plaque-binding anti-amyloid therapies, especially in patients carrying the APOE4 genotype, who face a substantially higher risk of treatment-related imaging abnormalities.

 Interim PRECISE-AD Results Support Favorable Safety Profile

PRECISE-AD (NCT06750432) is a randomized, double-blind, placebo-controlled Phase 1b trial evaluating intravenous PMN310 at doses of 5, 10, and 20 mg/kg in patients with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease.

The blinded interim analysis included 136 participants from the planned enrollment of 144 patients. Key findings included:

• No cases of ARIA-E across all genotypes.
• Overall, ARIA incidence of 4.4%, consisting exclusively of mild, asymptomatic ARIA-H (microhemorrhages).
• No treatment-related serious adverse events.
• No drug-related treatment discontinuations.
• Sixty-one percent of participants carried at least one APOE4 allele, including 11% who were APOE4 homozygotes, yet no ARIA-E events were reported in these higher-risk patients.

The absence of ARIA-E is particularly notable because APOE4 carriers, especially homozygotes, are known to experience the highest rates of ARIA with currently approved plaque-binding anti-amyloid therapies. While direct comparisons across clinical trials should be interpreted cautiously, the low incidence of mild ARIA-H and absence of ARIA-E support the hypothesis that selectively targeting toxic amyloid oligomers may reduce ARIA risk.

Blinded Biomarker Trends Suggest Target Engagement

Investigators also observed early movement in disease-relevant biomarkers. On a blinded basis, 68.5% of participants showed stable or reduced plasma phosphorylated tau 217 (pTau217), while 62.5% demonstrated stable or reduced cerebrospinal fluid MTBR-tau243 levels from baseline.

Because treatment assignments remain blinded, these biomarker trends are interpreted in the context of the trial’s 3:1 active-to-placebo randomization and are considered directionally consistent with target engagement. However, the observations do not establish treatment efficacy, and the relationship between these biomarker changes and future clinical outcomes will not be known until the study is unblinded.

Management Sees Early Validation of Differentiated Strategy

Chief Executive Officer Neil Warma said the interim findings reinforce the company’s strategy of selectively targeting toxic amyloid oligomers while avoiding plaque binding, a mechanism intended to separate therapeutic activity from the ARIA burden associated with current anti-amyloid therapies.

Behavioral neurologist Dr. Will Mantyh of the University of Minnesota noted that ARIA remains one of the primary barriers to prescribing existing amyloid-directed therapies. He said the absence of ARIA-E, together with favorable movement in plasma pTau217 and CSF MTBR-tau243, provides encouraging biological evidence ahead of the definitive 12-month analysis.

Unblinded Topline Results Expected in Early 2027

PRECISE-AD has completed enrollment of 144 participants across three dose cohorts receiving treatment for 12 months. The trial is evaluating safety, tolerability, pharmacokinetics, biomarkers, and exploratory clinical outcomes.

ProMIS expects to report unblinded 12-month topline results, including efficacy and safety data, in the first quarter of 2027. If the favorable safety profile and biomarker findings translate into meaningful clinical benefit, PMN310’s oligomer-selective mechanism could offer a differentiated therapeutic approach for early Alzheimer’s disease by reducing the ARIA burden that has limited broader use of plaque-binding anti-amyloid antibodies.

Reference

ProMIS Neurosciences Reports Positive Blinded Six-Month Interim Safety and Biomarker Data for PMN310 in the PRECISE-AD Phase 1b Alzheimer’s Disease Trial:: ProMIS Neurosciences, Inc. (PMN)