ProMIS Neurosciences announces publication on plasma pTau in Alzheimer’s

ProMIS Neurosciences (PMN) announced a publication in the peer-reviewed journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions. entitled, “Leveraging recent advances in plasma biomarkers to optimize early proof of concept trials in Alzheimer’s disease.” The analysis, conducted by Pentara Corporation in collaboration with scientists from ProMIS, provides important new evidence that plasma phosphorylated tau can serve as a meaningful primary endpoint in early-stage AD clinical trials, with potential to predict subsequent clinical benefit. Key Findings from the Publication Using summary data from several large monoclonal antibody trials in early AD, the analysis showed: Strong predictive relationship: Group level treatment effects on plasma pTau at 6 months were strongly correlated with treatment effects on the Clinical Dementia Rating Sum of Boxes at 12 months. Amplified signal, earlier readout compared to clinical outcomes: The effect size on plasma pTau was ~2.6 times larger than the effect size on CDR-SB, indicating that biomarker changes can be detected earlier and more robustly than clinical changes. Potential for smaller, more efficient trials: Simulations suggest that, for drugs with effect sizes similar to those seen with one of the leading mAbs, well-powered proof-of-concept trials using plasma pTau as a primary endpoint may require as few as ~100 participants. Together, these 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. ProMIS is currently conducting PRECISE-AD, an ongoing Phase 1b clinical trial of PMN310, its lead amyloid-beta targeting antibody, in patients with early Alzheimer’s disease. PMN310 is designed to selectively target toxic amyloid-beta oligomers, the species believed to be a primary driver of synaptic dysfunction and downstream disease pathology, while avoiding binding to monomers or plaque which is associated with higher rates of amyloid-related imaging abnormalities. The newly published analysis is directly aligned with, and supportive of, key elements of the PRECISE-AD design: Biomarker-centric strategy: PRECISE-AD incorporates plasma pTau as a central biomarker endpoint at 6 and 12 months, consistent with the timing and methodology highlighted in the publication. Early readout with potentially predictive value: By assessing plasma pTau changes as early as 6 months, PRECISE-AD is positioned to generate an early, quantitative signal of disease modification that can be used to model and predict future clinical outcomes. Efficient, de-risking design: The publication’s simulations reinforce that a biomarker-driven Phase 1b trial can be both smaller and faster, while still providing robust information to guide dose selection and go/no-go decisions for future trials including a pivotal Phase 3 trial. Mechanistic fit for PMN310: Because PMN310 is designed to neutralize toxic oligomers upstream of tau phosphorylation, meaningful reductions in plasma pTau could be expected if PMN310 successfully interrupts this pathogenic cascade.