INmune Bio reported new Phase 2 MRI data showing XPro improved white matter myelin integrity and cortical microstructure in early Alzheimer’s disease at Week 24, supporting biologic activity of selective soluble TNF inhibition.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
INmune Bio has reported new Phase 2 imaging findings showing that its investigational therapy XPro1595 (XPro) produced early treatment-related changes in brain microstructure in patients with early Alzheimer’s disease (AD). The data, which will be presented at the Alzheimer’s Association International Conference (AAIC) 2026, demonstrated statistically significant improvements in white matter myelin integrity at Week 24, providing further evidence of the drug’s biological activity through selective soluble tumor necrosis factor (TNF) inhibition.
The findings build on topline imaging results released in June 2026 from the Phase 2 MINDFuL study (NCT05318976). In the modified intent-to-treat population, XPro showed a statistically significant treatment effect on a white matter myelin biomarker compared with placebo (p < 0.01). Larger treatment effects were observed among patients selected using the company’s biomarker enrichment strategy.
Independent MRI Techniques Show Consistent Brain Microstructure Changes
The AAIC presentation expands the analysis by combining chi-separation imaging, which measures white matter myelin integrity using magnetic susceptibility, with cortical disarray measurement (CDM), an advanced diffusion MRI technique that evaluates gray matter microstructure.
Although the two imaging methods rely on different MRI acquisition techniques, processing pipelines, and tissue targets, both detected treatment-related changes in the same direction after 24 weeks. According to the investigators, this concordance strengthens the evidence that XPro is producing biologically meaningful effects on brain tissue rather than imaging artifacts.
Selective Soluble TNF Inhibition Targets Neuroinflammation
XPro selectively inhibits soluble TNF, a key inflammatory signaling molecule implicated in neurodegenerative diseases, while preserving transmembrane TNF signaling that supports normal immune function. Chronic neuroinflammation contributes to myelin damage, synaptic dysfunction, and progressive neuronal loss in Alzheimer’s disease, making soluble TNF an emerging therapeutic target.
Because alterations in white matter and cortical microstructure often occur before measurable brain atrophy develops, detecting treatment-related changes at 24 weeks may provide an earlier indication of therapeutic activity than conventional volumetric MRI endpoints.
Imaging Biomarkers May Detect Early Treatment Effects
Dr. CJ Barnum, Vice President of Neuroscience at INmune Bio, said the findings demonstrate that biomarkers of gray and white matter integrity can capture early pathological processes linked to cognitive decline. He noted that observing treatment effects on both white matter myelin and cortical microstructure within 24 weeks, using independent imaging approaches, supports the conclusion that XPro is engaging disease-relevant biological pathways earlier than traditional structural imaging would be expected to detect.
Chief Executive Officer David Moss added that improvements in myelination have remained one of the most consistent findings across the company’s preclinical and clinical research. He said the imaging results strengthen confidence that selective soluble TNF inhibition is achieving target engagement and may have broader applications across neurological diseases involving myelin injury.
AAIC 2026 Presentation and Next Steps
INmune Bio will present the expanded imaging analyses during the Developing Topics: Biomarkers poster session at AAIC 2026, taking place July 12-15 in London, United Kingdom. The poster will include longitudinal imaging analyses, subgroup findings, and additional mechanistic data for both white matter myelin integrity and cortical microstructure endpoints.
The new analyses further support the ongoing clinical development of XPro as a potential disease-modifying therapy for early Alzheimer’s disease and provide additional evidence that advanced MRI biomarkers may help detect biological treatment responses earlier in the disease course.
Reference
INmune Bio to Present Positive Phase 2 Imaging Data for XPro in Early Alzheimer’s Disease at AAIC
About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.