INmune Bio (INMB) Status Update summary

Trial overview and results

• The MINDFuL phase II trial was a double-blind, placebo-controlled study with 208 participants with early Alzheimer's disease and at least one inflammatory biomarker, randomized 2:1 (XPro:placebo) for 24 weeks.

• The primary endpoint (EMACC) was not met in the full mITT population, but a predefined subgroup of amyloid-positive patients with two or more inflammation biomarkers showed prevention of cognitive decline and clinically meaningful effect size (0.27) on EMACC.

• XPro showed cognitive, behavioral, and biological benefits in this subgroup, including improvements in EMACC, Neuropsychiatric Inventory, and pTau217 levels.

• The trial demonstrated that targeting neuroinflammation may slow cognitive decline in early Alzheimer's disease.

• Effect sizes for cognitive and behavioral endpoints were comparable to or better than those seen with anti-amyloid antibodies at 18 months, despite the trial's shorter six-month duration.

Safety and tolerability

• XPro was found to be safe, with no deaths, ARIA, or serious neurologic complications; the most common adverse event was manageable injection site reactions, leading to discontinuation in 10 patients.

• No organ toxicity, drug-related hospitalizations, or emergency interventions were reported; safety profile was consistent across age groups and ApoE4 status.

• Injection site reactions occurred in 80% of XPro patients but were generally mild and manageable, leading to improved management protocols during the trial.

• No restrictions were identified regarding concomitant medications, including anti-amyloid therapies or anticoagulants.

• The drug was considered safe for elderly patients with multiple comorbidities.

Biomarker and endpoint insights

• The subgroup analysis focused on amyloid-positive patients with multiple inflammation biomarkers, as these patients showed the most benefit.

• pTau217 was highlighted as a potent biomarker, with XPro showing favorable effects in the target population.

• The EMACC cognitive measure was validated as a sensitive and appropriate endpoint for future trials, minimizing demographic variance.

• Effect sizes ≥0.2 in early-phase AD trials are considered preliminary evidence of efficacy; XPro met this benchmark across multiple parameters.

• XPro is a selective soluble TNF inhibitor, aiming to reduce neuroinflammation while preserving normal TNF function.