Late Breaking Abstract - CosMx™ subcellular spatial molecular imaging of bronchial biopsies from patients with severe eosinophilic asthma treated with mepolizumab. Preliminary results of the MESILICO study.

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Background: MESILICO study has provided evidence of the effect of mepolizumab, an anti-IL-5 biologic, on airway remodeling in severe asthma at 12 months post-treatment ( NCT04612556 ). We continued to deeper characterisation of the cellular and molecular diversity of bronchial biopsies from these patients to provide insight into the pathophysiology of eosinophilic asthma. Methods: CosMx™ Spatial Molecular Imaging was undertaken of formalin-fixed paraffin embedded slides of bronchial biopsies collected at pre-treatment and 12 months post-treatment from patients with late-onset severe eosinophilic asthma with obstructive patterns that were administered mepolizumab (100mg SC every 4 weeks). Slides were stained and analysed on the NanoString CosMx™ SMI platform using the Human 6,000-plex Discovery Panel. Measurements and Main Results: Preliminary analysis found that from 2,651 cells profiled there were 3,216 genes above the lower limit of detection. Epithelial genes and innate immune cells were identified and changes in the expression of immunoglobulin genes evident with treatment. Changes in ligand-receptor interactions were observed between epithelial and immune cells. Conclusions: CosMx™ spatial profiling was able to profile distinct cell types in bronchial biopsies and identify anti-IL5 related changes in pathophysiology. These results extend understanding of Mepolizumab’s activity on the biology of asthma. GSK214163

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