Raymond J. Tesi, MD, INmune Bio, Boca Raton, FL, outlines the clinical development of XPro1595 for the treatment of Alzheimer’s disease (AD), sharing positive findings that support its continued investigation. XPro1595 is a protein biologic that targets soluble TNF (sTNF), designed based on evidence that suggests neuroinflammation is one of the prime drivers of neurodegeneration and cognitive decline. After demonstrating benefit in mouse models of AD (reduced brain amyloid deposition, reduced microglial activation, improved synaptic function, and improved cognition), a Phase Ib open-label safety and target engagement trial was launched in November 2019. The trial enrolled 20 patients with Alzheimer’s disease and evidence of peripheral inflammation. After three months, patients treated with the 1 mg/kg dose showed decreased neuroinflammatory markers on imaging (white-matter free water) and in the cerebrospinal fluid. Based on these data, two Phase II trials have been launched in people with mild AD and (NCT05318976) mild cognitive impairment (NCT05321498), respectively. As in the Phase I trial, participants must show signs of inflammation. The trials will randomize patients to receive 1 mg/kg XPro1595 or placebo in a 2:1 ratio, assessing six-month change in the Early and Mild Alzheimer’s Cognitive Composite (EMACC) as the primary outcome measure. This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.