お知らせ • Jun 02
INmune Bio Reports Statistically Significant Treatment Effect On Advanced White Matter MRI Biomarker In Phase 2 MINDFuL Alzheimer's Trial
INmune Bio Inc. announced results from exploratory chi-separation (?-separation) MRI imaging analyses from the MINDFuL Phase 2 clinical trial of XPro™ (XPro1595) in patients with early Alzheimer's disease encompassing both mild cognitive impairment (MCI) and mild Alzheimer’s disease dementia. The new MRI findings add to a growing body of evidence supporting XPro™’s precision-medicine development strategy, including the peer-reviewed publication of the Phase 2 MINDFuL results in NPJ Dementia, FDA End-of-Phase 2 alignment on an integrated Phase 2b/3 registrational pathway, and the recent grant of FDA Fast Track designation for XPro™ in early Alzheimer’s disease. Across multiple independent preclinical models of demyelination and neurological injury, white matter has consistently emerged as the most reliable and reproducible target of XPro™ response, with clear, documented effects on myelin volume and quality. While historical industry efforts in AD have focused heavily on gray matter pathology, white matter (WM) degeneration and myelin loss are increasingly recognized as fundamental, early contributors to cognitive decline. Chi-separation MRI was included in the MINDFuL Phase 2 trial as a target engagement biomarker for white matter. This method was chosen given that the trial enrolled patients with MCI and mild AD, the disease stage at which white matter abnormalities are prominent and highly clinically relevant. Chi-separation is a recently validated imaging technique that resolves key challenges of conventional MRI myelin measurement and can be deployed across standard multi-site clinical infrastructure without requiring specialty scanners, making it a methodologically superior and operationally scalable measure of white matter biology. The blinded analysis, performed by an independent imaging core laboratory, revealed statistically significant treatment effect on myelin: Full mITT Population (N=200): After 24 weeks of treatment, XPro™-treated participants showed a statistically significant difference in myelin compared to placebo (p=0.0028) with a medium effect size (Cohen's d=0.46). This effect across the full treatment population reproduces XPro™'s most reliable preclinical signature, establishing target engagement in AD patients with a high degree of confidence. Biomarker-Enriched AD Population (N=100): In patients with amyloid-positivity and two or more elevated inflammatory biomarkers at baseline, the treatment effect strengthened further to a medium-to-large effect size (Cohen's d=0.59; p=0.0098). This is the patient profile most directly aligned with XPro™'s anti-neuroinflammatory mechanism. INmune Bio will present the complete chi-separation dataset from the MINDFuL study, including longitudinal trajectory analysis, subgroup characterization, dose-response analyses, and mechanistic interpretation at the Alzheimer's Association International Conference (AAIC) 2026 which will take place July 12–15, 2026 in London, UK. The presentation will also include data from complementary advanced MRI endpoints in the MINDFuL imaging package. Additional details will be announced following the presentation. Following a successfully completed End-of-Phase 2 meeting, INmune Bio has secured regulatory alignment with the FDA on the design of its upcoming registrational program, establishing a clear, de-risked pathway toward commercial submission. Supported by FDA Fast Track designation granted on May 14, 2026, the Phase 2b/3 seamless adaptive trial is engineered to support the registration of XPro™ in patients with early Alzheimer's disease who carry biomarkers of inflammation. The registrational strategy is also supported by the favorable safety profile observed in the Phase 2 MINDFuL trial, including no observed ARIA-E or ARIA-H, an important differentiating feature for a disease-modifying Alzheimer’s program focused on neuroinflammation rather than amyloid clearance. Phase 2b Adaptive Advancement: The Phase 2b portion of the study will utilize the Early Alzheimer's Disease Cognitive Composite (EMACC) and plasma pTau217 as rigorous, decision-gating endpoints. These metrics will dictate the adaptive advancement of the program into the Phase 3 cohort. Phase 3 Registrational Evaluation: The Phase 3 portion is expected to evaluate definitive clinical outcomes, including the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB), which the FDA has raised no objections to using as the sole primary efficacy endpoint for the Phase 3 registrational portion of the program. XPro1595 is a next-generation inflammatory cytokine modulator that neutralizes soluble TNF (sTNF) without affecting transmembrane TNF (tmTNF) or its receptors. This selective targeting is designed to reduce neuroinflammation, a key driver of neurodegeneration in Alzheimer’s disease, while maintaining the protective immune functions of the body. INmune Bio is actively advancing two late-stage product platforms toward registrational milestones: CORDStrom™: A proprietary, pooled, allogeneic, human umbilical cord-derived mesenchymal stromal cell (hucMSC) platform engineered to address the historical clinical challenges of donor variability and manufacturing inconsistency. Following successful clinical readouts in Recessive Dystrophic Epidermolysis Bullosa (RDEB), the platform is transitioning to regulatory filing phases, with a Marketing Authorization Application (MAA) scheduled for the UK MHRA and EU EMA in 2026, alongside a planned U.S. Biologics License Application (BLA) submission. XPro™: A Dominant-Negative Tumor Necrosis Factor (DN-TNF) platform that selectively neutralizes soluble TNF (sTNF) to eliminate neuroinflammation without compromising protective immune function. Backed by recently granted FDA Fast Track designation and successful regulatory alignment from an End-of-Phase 2 meeting, XPro™ is positioned for an integrated Phase 2b/3 seamless adaptive registrational program in neuroinflammation-enriched early Alzheimer's disease.