New cross-trial analysis supports the biomarker’s potential to predict clinical benefit, reinforcing biomarker-driven trial designs.
A new peer-reviewed analysis suggests plasma phosphorylated tau (pTau) biomarkers can serve as meaningful primary endpoints in early-stage Alzheimer’s disease clinical trials, with potential to predict subsequent clinical benefit.
The analysis, published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions, was conducted by Pentara Corp in collaboration with scientists from ProMIS Neurosciences Inc. Using summary data from several large monoclonal antibody trials in early Alzheimer’s disease, researchers found that plasma pTau181 and pTau217 changes at six months correlated with clinical outcomes measured at 18 months.
The findings support the use of plasma pTau as a primary endpoint in early clinical development and as a quantitative bridge to predict future clinical outcomes, according to the researchers.
“Our analysis shows that plasma pTau not only tracks disease biology, but also robustly predicts clinical outcomes across multiple monoclonal antibody trials,” says Larry D Altstiel, MD, PhD, chief medical officer of ProMIS and a co-author on the paper, in a release.
Supporting Biomarker-Driven Trial Design
The analysis supports the design of ProMIS’ ongoing PRECISE-AD Phase 1b clinical trial, which is evaluating PMN310, the company’s lead amyloid-beta targeting antibody, in patients with early Alzheimer’s disease. PMN310 is designed to selectively target toxic amyloid-beta oligomers while avoiding binding to monomers or plaque, which is associated with higher rates of amyloid-related imaging abnormalities.
The PRECISE-AD trial incorporates plasma pTau217 as a primary biomarker endpoint, with a planned six-month interim analysis expected in the second quarter of 2026.
“The ability to link a six-month plasma readout to later clinical benefit means we can make smarter, earlier decisions about PMN310’s development path, while using capital more efficiently,” says Neil Warma, chief executive officer of ProMIS Neurosciences, in a release.
Practical Applications for Trial Optimization
The cross-trial analysis quantified how strongly early plasma pTau changes predicted later clinical outcomes across multiple well-characterized Alzheimer’s disease trials. The magnitude of this relationship, combined with the biomarker signal being easier to detect than clinical signals, makes plasma pTau an attractive primary endpoint for early proof-of-concept studies.
“By combining data across several large, well-characterized AD trials, we were able to quantify how strongly early plasma pTau changes predicted later clinical outcomes,” says Suzanne Hendrix, PhD, CEO of Pentara Corp and a co-author on the paper, in a release. “This approach has the potential to reduce trial size and duration while increasing confidence in the decisions sponsors must make as they advance into Phase 3 pivotal studies.”
The PRECISE-AD trial is a randomized, double-blind, placebo-controlled study evaluating multiple ascending doses of intravenous PMN310 in patients with mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease. The study has targeted enrollment of 128 patients and is designed to provide 95% confidence for detection of amyloid-related imaging abnormalities.
PMN310 received Fast Track designation from the US Food and Drug Administration in July 2025. Final top-line data from the PRECISE-AD trial is expected in the fourth quarter of 2026.
D 168502358 | Alzheimer © Designer491 | Dreamstime.com
