Strategy Confirmed With FDA for Phase 2b/3 Study of XPro1595 to Treat Early Alzheimer Disease

INmune Bio confirmed receipt of notes from the US Food and Drug Administration (FDA) on continuing the proposed integrated phase 2b/3 clinical development of XPro1595 for early Alzheimer disease. The company aligned regulatory strategy with FDA recommendations and will continue its drug development strategy.

“The outcome of the End-of-Phase 2 interaction is an important inflection point for XPro1595,” said CJ Barnum, PhD, vice president of neuroscience at INmune Bio. “The FDA’s feedback on our enrichment-led design, primary endpoint, and integrated Phase 2b/3 structure validates our scientific and clinical strategy and provides a clearly defined regulatory path to advancing XPro1595 into a registration-intent program in early Alzheimer disease,” he added.

The FDA’s recommendations were consistent with the company’s approach for an enrichment-led design to identify patients with inflammatory biomarker profiles linked to soluble tumor necrosis factor (TNF) signaling. FDA review was based on the phase 2 clinical data package, which included cognitive and biomarker analyses. Meeting with the FDA indicated alignment on phase 2b/3 framework design, primary endpoint, biomarker-driven strategy, and exploratory cohort.

The phase 2b study will include an integrated design, with approximately 300 participants over a 9-month evaluation period to validate efficacy and biomarkers assumptions before the phase 3 element continues. The complete phase 3 program is expected to enroll over 1000 participants, evaluating over 18 months. For a primary efficacy endpoint, the study will use the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB). Patients will be enrolled based on 2 or more biomarkers associated with peripheral inflammation and immune-mediated disease risk (high sensitivity C-reactive protein, erythrocyte sedimentation rate, hemoglobin A1c, and apolipoprotein E4), which are known to be linked with soluble TNF signaling. The FDA recommended the trial include an exploratory cohort of nonenriched early Alzheimer disease patients to assess the larger effect of XPro1595.

In phase 2b, a 9-month evaluation period will establish evidence for continuation into phase 3. Assessments in the phase will include the Early Mild Alzheimer Cognitive Composite and plasma p-tau-217. These endpoints in phase 2b are thought to show sensitivity to early changes in shorter treatment periods. Then, in phase 3, the sole primary endpoint will use the CDR-SB as a global functional outcome measure.

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

“Our end-of-phase 2 interaction with the FDA reflects alignment between our proposed development strategy and the Agency’s expectations for late-stage Alzheimer programs,” said David Moss, MBA, chief executive officer of INmune Bio. “XPro1595 represents a differentiated approach to Alzheimer disease, based on precision patient selection and selective immune modulation, with a favorable safety profile that included zero cases of [amyloid-related imaging abnormalities] in our phase 2 study. We appreciate and thank the FDA for its constructive engagement and look forward to advancing XPro1595 in a registration-directed program.”

INmune will incorporate FDA feedback into the final protocol for the phase 2b/3 study and anticipates submitting the protocol for review.

References

1. INmune Bio announces FDA alignment on integrated phase 2b/3 registration pathway for XPro1595 in early Alzheimer disease. Press release. February 12, 2026. Accessed February 12, 2026. https://finance.yahoo.com/news/inmune-bio-announces-fda-alignment-120000419.html

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.