Phase 2 MINDFul Trial Results on XPro1595 for Early Alzheimer Disease With Inflammation

INmune Bio today announced that results from its phase 2 MINDFuL trial that evaluated the safety, biomarker engagement, and clinical efficacy of XPro (XPro1595, pegipanermin) in patients with mild Alzheimer disease (AD) characterized by biomarkers of inflammation. In a prespecified analysis of the protocol-defined AD with inflammation (ADi) subgroup, XPro showed directionally consistent benefit across cognitive, global, functional, behavioral, and biomarker endpoints over 24 weeks, with no amyloid-related imaging abnormalities (ARIA) observed.¹ However, XPro1595 did not show statistical significance on the primary endpoint within the overall study population.

XPro1595 is a TNF inhibitor currently in clinical trial. The drug neutralizes soluble TNF without affecting transmembrane TNF or TNF receptors. It could have beneficial effects in patients with neurologic disease, as it decreases neuroinflammation. Targeting inflammation is thought to be useful in improving cognitive function and neuronal communication.²

"MINDFuL is the first peer-reviewed trial to prospectively identify Alzheimer's patients by both amyloid pathology and a biomarker-defined inflammatory signature. In this prespecified subgroup, we observed directional improvements across cognitive, global, functional, behavioral, and biomarker endpoints, with no ARIA. The cross-domain consistency tracks with the underlying biology and represents the type of signal a phase 2 trial is designed to identify, forming the foundation of a phase 3 program,” said CJ Barnum, PhD, the vice president of neuroscience at INmune Bio.

The results have been published in the peer-reviewed journal NPJ Dementia, entitled "XPro1595 in Early Alzheimer's Disease with Inflammation: Results from the Phase 2 MINDFuL Trial."³ This publication discusses how XPro demonstrated consistent positive trends in a prespecified enriched subpopulation (n=100) with amyloid-beta positivity and 2 or more inflammation biomarkers (hsCRP, ESR, HbA1c, or APOE ε4 allele). The paper further highlights the effect sizes (Cohen's d) up to 0.27 across cognitive (EMACC, International Shopping List Test), Patient-Reported Outcomes (Goal Attainment), behavioral (Neuropsychiatric Inventory), and biomarker endpoints (pTau217 and GFAP), directionally consistent with an XPro treatment effect. These findings support prioritization of the enriched population in future studies to optimize detection of treatment effects.

“MINDFuL provides interesting and valuable insights into selective soluble TNF inhibition as a potential therapeutic approach for early Alzheimer disease. While XPro1595 did not show statistical significance on the primary endpoint within the overall study population, a prespecified subset of participants, enriched for the presence of amyloid and inflammatory biomarkers (ADi), demonstrated consistent directional patterns favoring XPro1595 across cognitive and neuropsychiatric outcomes. This biomarker-enriched analysis, supported by comparable numerical differences in pTau217 and GFAP, reveals important mechanistic and clinical findings that warrant careful consideration for future development strategies,” concluded the study authors.³

The authors also specifically noted the importance of the absence of ARIA, which is a crucial distinction from other treatments currently available. Many therapeutic offerings have elevated risks of cerebrovascular events in vulnerable populations, especially APOE ε4 carriers, who make up a large proportion of patients with AD.^4,5

"The publication of the phase 2 results from MINDFuL in NPJ Dementia, together with the FDA Fast Track designation, strengthens the value of the XPro platform. The trial also supports a biomarker-enriched (inflammation-enriched) strategy designed to improve future trial design and enhance the potential for clinical success, while reinforcing the broader potential of selective sTNF neutralization across inflammation-driven diseases,” shared David Moss, the chief executive officer of INmune Bio.

References

1. INmune Bio publishes phase 2 MINDFuL trial results in NPJ Dementia, advancing the XPro™ platform. News release. May 15, 2026. Accessed May 15, 2026. https://www.benzinga.com/pressreleases/26/05/g52592939/inmune-bio-publishes-phase-2-mindful-trial-results-in-npj-dementia-advancing-the-xpro-platform

2. Kinney JW, Bemiller SM, Murtishaw AS, et al. Inflammation as a central mechanism in Alzheimer's disease. Alzheimers Dement (N Y). 2018;4:575-590.

3. Jaeger J, Staats KA, Barnum S, et al. XPro1595 in early Alzheimer’s disease with inflammation: results from the phase 2 MINDFuL trial. NPJ Dementia. 2026;37(2).

4. Foley KE, Wilcock DM. Three major effects of APOEε4 on Aβ immunotherapy induced ARIA. Front Aging Neurosci. 2024;16:1412006.

5. Zimmer JA, Ardayfio P, Wang H, et al. Amyloid-related imaging abnormalities with donanemab in early symptomatic Alzheimer disease: secondary analysis of the TRAILBLAZER-ALZ and ALZ 2 randomized clinical trials. JAMA Neurol. 2025;82(5):461.