XPro1595 Phase 2 MINDFuL Results Published; FDA Aligns on Phase 2b/3 Registrational Plan

INmune Bio Inc. announced that results from its Phase 2 MINDFuL trial of XPro1595 (pegipanermin) in early Alzheimer’s disease with inflammation have been published in the peer-reviewed journal NPJ Dementia, and that the FDA has aligned on an integrated phase 2b/3 registrational program for the drug.

In the pre-specified Alzheimer’s disease with inflammation (ADi) subgroup, XPro showed directionally consistent benefit across cognitive, global, functional, behavioral, and biomarker endpoints over 24 weeks, with no amyloid-related imaging abnormalities (ARIA) observed. The publication, titled “XPro1595 in Early Alzheimer’s Disease with Inflammation: Results from the Phase 2 MINDFuL Trial,” reported consistent positive trends in a pre-specified enriched subpopulation (n=100) with amyloid-beta positivity and two or more inflammation biomarkers (hsCRP, ESR, HbA1c, or APOE ε4 allele). Effect sizes (Cohen’s d) reached up to 0.27 across cognitive (EMACC, International Shopping List Test), patient-reported outcomes (Goal Attainment), behavioral (Neuropsychiatric Inventory), and biomarker endpoints (pTau217 and GFAP).

The company received FDA feedback supporting advancement to a registrational study in patients with Alzheimer’s disease with biomarkers of inflammation. The FDA’s recommendations were consistent with an enrichment-led design to identify patients with inflammatory biomarker profiles linked to soluble tumor necrosis factor (TNF) signaling. The integrated phase 2b/3 design includes approximately 300 participants in phase 2b over a 9-month evaluation period to validate efficacy and biomarker assumptions before the phase 3 element continues. The complete phase 3 program is expected to enroll over 1000 participants, evaluated over 18 months, with the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) as the primary efficacy endpoint. Patients will be enrolled based on two or more biomarkers associated with peripheral inflammation and immune-mediated disease risk (high-sensitivity C-reactive protein, erythrocyte sedimentation rate, hemoglobin A1c, apolipoprotein E4). The FDA recommended the trial include an exploratory cohort of nonenriched early Alzheimer’s disease patients.

The vice president of neuroscience at INmune Bio said the MINDFuL trial is the first peer-reviewed trial to prospectively identify Alzheimer’s patients by both amyloid pathology and a biomarker-defined inflammatory signature, and that the cross-domain consistency forms the foundation of a Phase 3 program. The CEO said the FDA’s feedback on the enrichment-led design, primary endpoint, and integrated Phase 2b/3 structure validates the company’s scientific and clinical strategy, and noted the phase 2 study had zero cases of ARIA.

INmune Bio will host a webinar on February 27, 2026, at 9:30 a.m. ET focusing on the registrational pathway of XPro1595, covering MINDFuL trial results, FDA feedback, and the path to Phase 3.