XPro™ Shows Cognitive and Biomarker Benefits in Phase 2 Alzheimer’s Trial

INmune Bio announced publication of results from its Phase 2 MINDFuL trial (NCT05318976) evaluating XPro™ (XPro1595, pegipanermin) in patients with early Alzheimer’s disease. The study was published in the peer-reviewed journal NPJ Dementia.

The randomized, placebo-controlled trial assessed the safety, biomarker engagement, and clinical activity of XPro™, a selective inhibitor of soluble tumor necrosis factor (sTNF). The therapy is designed to block inflammatory TNFR1 signaling while preserving transmembrane TNF/TNFR2 pathways involved in normal immune and repair functions.

A key focus of the study was a pre-specified, protocol-defined subgroup of patients with Alzheimer’s disease and inflammation (ADi). This biomarker-enriched subgroup included 100 patients with amyloid-beta positivity and at least two inflammatory markers, including hsCRP, ESR, HbA1c, or the APOE ε4 allele.

At 24 weeks, patients treated with XPro™ in the ADi subgroup showed directionally consistent improvements across cognitive, functional, behavioral, global, and biomarker measures compared with placebo. The findings suggest potential clinical and biological activity in Alzheimer’s patients with inflammatory signatures.

Reported effect sizes (Cohen’s d) reached up to 0.27 across several endpoints, including the Early Mild Alzheimer’s Cognitive Composite (EMACC), International Shopping List Test, Goal Attainment patient-reported outcomes, Neuropsychiatric Inventory scores, and biomarkers pTau217 and GFAP. While modest, these effect sizes are within the range commonly reported in early-stage Alzheimer’s disease trials.

The biomarker findings also indicated target engagement on pTau217 and GFAP, supporting the proposed effect of XPro™ on neuroinflammatory and neurodegenerative pathways.

No amyloid-related imaging abnormalities (ARIA) were observed during the study, a notable finding given the safety concerns associated with several anti-amyloid antibody therapies. Overall tolerability and adverse event rates were reported as generally comparable between treatment groups, with no new safety signals identified in the ADi subgroup.

The authors stated that prospectively enriching Alzheimer’s trials using both amyloid pathology and inflammatory biomarkers may improve detection of treatment effects in selected patient populations.

CJ Barnum, Vice President of Neuroscience at INmune Bio, said the MINDFuL study is the first peer-reviewed Alzheimer’s trial to prospectively identify patients using both amyloid pathology and biomarker-defined inflammation. He noted that the consistent directional findings across clinical and biomarker measures, together with the absence of ARIA, support further development of XPro™ in Phase 3 studies.

David Moss, Chief Executive Officer of INmune Bio, said the publication, along with the FDA Fast Track designation previously granted to XPro™, supports the company’s inflammation-enriched development strategy for Alzheimer’s disease.

The company noted that some endpoint findings remain exploratory and that the Phase 2 study was not powered to establish definitive efficacy across all individual clinical measures within the ADi subgroup. INmune Bio plans to advance XPro™ into Phase 3 development using an inflammation-enriched enrollment strategy informed by the MINDFuL data.

Reference

INmune Bio Publishes Phase 2 MINDFuL Trial Results in NPJ Dementia, Advancing the XPro™ Platform

Study Details | NCT05318976 | A Study of XPro1595 in Patients with Early Alzheimer’s Disease with Biomarkers of Inflammation | ClinicalTrials.gov

Jaeger, J., Staats, K.A., Barnum, S. et al. XPro1595 in early Alzheimer’s disease with inflammation: results from the phase 2 MINDFuL trial. npj Dement. 2, 37 (2026). https://doi.org/10.1038/s44400-026-00091-x