INmune Bio, Inc. announced that results from a Phase 1b study demonstrate that XPro1595, an investigational dominant-negative protein that neutralizes soluble TNF, decreases biomarkers of neuroinflammation across multiple measures and assays, including cerebrospinal fluid (CSF) and MRI, in patients with Alzheimer’s disease (AD). The data suggest that decreasing neuroinflammation results in significant improvements in biomarkers of neurodegeneration and synaptic function. The goal of the ongoing Phase 1b open label dose escalation trial is to demonstrate that XPro1595, when given as a subcutaneous injection once weekly, will decrease neuroinflammation in patients with mild to moderate AD. The data shows that cytokine/chemokine CSF levels after 12 weeks of therapy were decreased, with multiple statistically significant reductions (e.g., c-reactive protein (CRP) & YKL-40, p<0.0001). Additionally, there was a significant correlation between neuroinflammation, as measured by CSF, and MRI white matter free water (R2=0.75; p<0.01), a validated biomarker of neuroinflammation. This supports the use of white matter free water as a neuroinflammatory biomarker of treatment response in future studies. Proteomic CSF analysis revealed that targeting neuroinflammation led to a significant change in multiple AD-related pathways including immune/inflammatory response, CNS neuronal function and injury, dendritic spine morphogenesis and synaptic plasticity. Notably, the analysis found an approximate two-fold reduction in the neurodegeneration markers visinin-like protein 1 (VILIP-1) and neurofilament light (NFL), and an approximate three-fold change in contactin-2 and a half-fold change in neurogranin, both proteins associated with synaptic plasticity (p<0.0001).