XPro1595 in early Alzheimer’s disease with inflammation: results from the phase 2 MINDFuL trial
6 affiliations
- 1Cognition Metrics, LLC, Hixon, TN, USA
- 2INmune Bio, Inc, Boca Raton, FL, USA
- 3Psychological Assessment and Consulting Services, PLLC, Geneva, NY, USA
- 4Allucent, Cary, NC, USA
- 5Toronto Memory Program, Toronto, ON, Canada
- 6Department of Neurology, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA
Abstract
Alzheimer’s disease (AD) involves chronic neuroinflammation driven by tumor necrosis factor (TNF). XPro1595 selectively neutralizes pathological soluble TNF while preserving neuroprotective transmembrane TNF signaling. MINDFuL (clinicaltrials.gov NCT05318976, registration April 1st 2022) was a Phase 2, multicenter, randomized, double-blind, placebo-controlled, proof-of-concept study. Participants with Early AD and elevated inflammatory biomarkers received XPro1595 (1.0 mg/kg) or placebo for 24 weeks with Early Mild Alzheimer’s Cognitive Composite (EMACC) as the primary endpoint. A prospectively defined biomarker-enriched population included amyloid-positive participants with ≥2 inflammatory markers (ADi). The mITT population ( n = 200) showed no difference in EMACC ( p = 0.672). However, the ADi population ( n = 100) showed signals across multiple clinical endpoints favoring XPro1595, including the EMACC (Cohen’s d = 0.27), Neuropsychiatric Inventory ( d = −0.23), particularly the subfactor agitation/hyperactivity (d = −0.37), and the Goal Attainment Scale ( d = 0.18). Accordingly, in ADi, XPro1595 attenuated plasma pTau217 ( d = −0.18) and GFAP ( d = −0.19). Many effect sizes were larger in participants with higher drug exposure. Notably, no amyloid-related imaging abnormalities (ARIA) were observed. While XPro1595 did not meet the primary endpoint in mITT, in ADi consistent directional patterns favoring XPro1595 across cognitive and neuropsychiatric outcomes were observed. These findings support XPro1595 as an interesting therapeutic for persons with AD and elevated inflammatory burden.
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BibTeX
@article{jaeger2026xpro1595,
title = {{XPro1595 in early Alzheimer’s disease with inflammation: results from the phase 2 MINDFuL trial}},
author = {Judith Jaeger and Kim A. Staats and Sarah Barnum and Parris Pope and Lisle R. Kingery and Melanie Buitendyk and Sharon Cohen and Malú G. Tansey and Raymond J. Tesi and Christopher J. Barnum},
journal = {npj Dementia},
year = {2026},
month = may,
doi = {10.1038/s44400-026-00091-x},
url = {https://doi.org/10.1038/s44400-026-00091-x},
note = {CC BY},
}
RIS
TY - JOUR
TI - XPro1595 in early Alzheimer’s disease with inflammation: results from the phase 2 MINDFuL trial
AU - Judith Jaeger
AU - Kim A. Staats
AU - Sarah Barnum
AU - Parris Pope
AU - Lisle R. Kingery
AU - Melanie Buitendyk
AU - Sharon Cohen
AU - Malú G. Tansey
AU - Raymond J. Tesi
AU - Christopher J. Barnum
PY - 2026
DA - 2026/05/13
JO - npj Dementia
DO - 10.1038/s44400-026-00091-x
UR - https://doi.org/10.1038/s44400-026-00091-x
AB - Alzheimer’s disease (AD) involves chronic neuroinflammation driven by tumor necrosis factor (TNF). XPro1595 selectively neutralizes pathological soluble TNF while preserving neuroprotective transmembrane TNF signaling. MINDFuL (clinicaltrials.gov NCT05318976, registration April 1st 2022) was a Phase 2, multicenter, randomized, double-blind, placebo-controlled, proof-of-concept study. Participants with Early AD and elevated inflammatory biomarkers received XPro1595 (1.0 mg/kg) or placebo for 24 weeks with Early Mild Alzheimer’s Cognitive Composite (EMACC) as the primary endpoint. A prospectively defined biomarker-enriched population included amyloid-positive participants with ≥2 inflammatory markers (ADi). The mITT population ( n = 200) showed no difference in EMACC ( p = 0.672). However, the ADi population ( n = 100) showed signals across multiple clinical endpoints favoring XPro1595, including the EMACC (Cohen’s d = 0.27), Neuropsychiatric Inventory ( d = −0.23), particularly the subfactor agitation/hyperactivity (d = −0.37), and the Goal Attainment Scale ( d = 0.18). Accordingly, in ADi, XPro1595 attenuated plasma pTau217 ( d = −0.18) and GFAP ( d = −0.19). Many effect sizes were larger in participants with higher drug exposure. Notably, no amyloid-related imaging abnormalities (ARIA) were observed. While XPro1595 did not meet the primary endpoint in mITT, in ADi consistent directional patterns favoring XPro1595 across cognitive and neuropsychiatric outcomes were observed. These findings support XPro1595 as an interesting therapeutic for persons with AD and elevated inflammatory burden.
SN - 3005-1940
ER -