XPro1595 in Early Alzheimer Disease With Inflammation: Phase 2 MINDFuL Trial Results Submitted for Publication

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INmune Bio today announced the submission of the results of the phase 2 MINDFuL trial on XPro1595, a selective soluble tumor necrosis factor (TNF) neutralizer, in early Alzheimer disease with inflammation (ADi), for peer review to npj Dementia.^1,2

XPro1595 (XPro) is a next-generation inhibitor of TNF that is currently under investigation in clinical trials. XPro acts differently than currently available TNF inhibitors; it neutralizes soluble TNF (sTNF), without affecting trans-membrane TNF (tmTNF) or TNF receptors, offering a mechanistically distinct approach from current amyloid-targeting therapies. Investigators believe XPro could have potential substantial beneficial effects in patients with neurologic disease by decreasing neuroinflammation.

The submitted manuscript provides a comprehensive analysis of the MINDFuL trial—a phase 2, multicenter, randomized, double-blind, placebo-controlled study conducted across 35 centers in 8 countries—which evaluated the safety and efficacy of XPro in participants with early Alzheimer disease and biological signs of inflammation. Participants aged 50 to 85 years with early AD (mild cognitive impairment or mild dementia) and elevated inflammatory biomarkers received weekly subcutaneous injections of XPro1595 (1.0 mg/kg) or placebo for 24 weeks. The primary endpoint was the Early Mild Alzheimer's Cognitive Composite. The study did not meet its primary endpoint in the overall population; however, the data reveal a promising signal in a prespecified subgroup of patients with both amyloid pathology and a high inflammatory burden, defined by 2 or more biomarkers of inflammation, referred to as the ADi population. Of the 206 randomly assigned participants, 200 comprised the modified intent-to-treat (mITT) population and 100 comprised the ADi population.

"The publication of the MINDFuL trial results with the scientific community highlight the potential therapeutic value of our XPro platform. We are encouraged by the trial results of the subgroup analysis, in addition to the demonstrated strong safety profile, which we believe favorably positions XPro for clinical trial advancement," said CJ Barnum, the VP of Neuroscience at INmune Bio.

XPro demonstrated consistent positive trends across cognitive, neuropsychiatric, and biological endpoints, which suggests that targeting neuroinflammation by selectively neutralizing soluble TNF may offer benefits for a very specific subset of individuals living with Alzheimer disease. This supports continued development of XPro as a precision medicine approach for this patient group. Additionally, there was also a complete absence of amyloid-related imaging abnormalities, a serious adverse effect commonly associated with amyloid-targeting therapies. This favorable safety profile was observed in a high-risk patient population, including significant numbers of APOE4 carriers (approximately 70% of participants), patients receiving anticoagulant medications, and individuals with multiple cerebral microbleeds (approximately 33% of participants). Notably, this distinguishes XPro from other treatments and suggests its potential for broader use.

"Data in the subgroup analysis strongly suggests XPro will benefit the trial's target patient population while also providing a strong rationale for our upcoming end-of-phase 2 discussions with regulatory authorities, including the FDA, EMA, and MHRA," said David Moss, the CEO of INmune Bio. "We anticipate receiving regulatory feedback from the FDA in the first quarter of 2026."

References

1. INmune Bio announces submission of phase 2 MINDFuL trial results in Alzheimer's disease to npj Dementia, a Nature Portfolio journal. News release. September 29, 2025. Accessed September 29, 2025. https://www.benzinga.com/pressreleases/25/09/g47912826/inmune-bio-announces-submission-of-phase-2-mindful-trial-results-in-alzheimers-disease-to-npj-deme

2. Jaeger J, Staats KA, Barnum S, et al. XPro1595, a selective soluble TNF neutralizer, in early Alzheimer's disease with inflammation (ADi): results from the phase 2 MINDFuL trial. Preprint. September 27, 2025. Accessed September 29, 2025. https://www.medrxiv.org/content/10.1101/2025.09.24.25336496v1