822 RPT193, a CCR4 inhibitor, improves the inflammatory skin transcriptomic profile in patients with atopic dermatitis

The chemokine receptor CCR4 mediates CCL17- and CCL22-driven chemotaxis of Th2 cells into the skin patients with atopic dermatitis (AD). RPT193 is an oral inhibitor that has been developed to treat AD other allergic inflammatory diseases. safety efficacy as monotherapy for moderate-to-severe was previously described in a placebo-controlled, double-blinded Phase 1 study. Here, we present peripheral biomarker analysis from this trial. Following 28 days 400 mg daily treatment, RNA-seq and/or RT-PCR demonstrated significant downregulation general inflammation- (MMP12; p<0.01), innate immunity- (IL8; T-cell/T-cell activation- (IL2, CCL19, CCR7, ICOS; p<0.05), Th1- (CCL2; Th2- (CCL22, CCR4; Th17/Th22-related markers (IL22, CCL20, CCR6, S100A8, S100A9, S100A12, PI3/Elafin; p<0.05) compared baseline RPT193-treated, but not placebo-treated, subjects. Significant modulation also seen placebo genes related inflammation, T-cell activation, T helper subsets (MMP12, IL-2, ICOS, DEFB4, IL-22, p<0.05). We observed decreased surface expression on circulating no major changes abundance subsets. In conclusion, these data suggest treatment improves transcriptome, consistent clinical efficacy, well decreases periphery. A 2 study planned investigate moderate severe AD.