563 ATx201 modulates biomarkers of skin barrier function and cutaneous inflammation in patients with moderate atopic dermatitis

ATx201 is a small molecule, which decolonizes Staphylococcus aureus and improves the diversity of the skin microbiome in patients with mild-to-severe atopic dermatitis (AD) (DECOLAD). We now report the safety and immune-modulatory effect of ATx201 in patients with moderate AD. In this randomized, double-blind, intraindividual, and vehicle-controlled Phase 2 trial, thirty-one patients received ATx201 CREAM 2% and matching vehicle (1:1) once daily for 3 weeks (NCT03304470), with a 12-day follow-up period. Analysis of the safety data revealed that ATx201 CREAM 2% was generally safe and well-tolerated in subjects with moderate AD lesions. The histological and transcriptional profiling analysis (IHC, microarray and RT-PCR) demonstrated that treatment with ATx201 CREAM 2% significantly (p < 0.05) increased expression of biomarkers related to skin barrier function (PNPLA3, ACOX2, DGAT2, FAXDC2, etc.), and decreases expression levels of markers related to inflammation including Th17 (S100A7, S100A9, CCL20, PI3, CXCL1, IL17C, STAT3), Th2 (IL10, IL4R, CCL26, CCL18, etc.), Th1 (CCL2, CCR1, etc.) and inflammatory cells (Langerin/CD207) compared to vehicle at Day 22. Finally, several biomarkers that were significantly modulated by ATx201 CREAM 2% were significantly correlated with improvement in TSS, TAA scores and the TSS component scores (p < 0.05), such as S100A8 (ρ_TSS = 0.83), KRT16 (ρ_TSS = 0.77), PI3 (ρ_TSS = 0.69), IL13 (ρ_TSS = 0.68), IL22 (ρ_TSS = 0.67) and MMP12 (ρ_TSS = 0.55). IHC analysis further revealed that 15/29 (51.7%) subjects were classified as histological responders receiving ATx201 CREAM 2% versus 9/29 (31.0%) receiving vehicle. These data suggest that topical application of ATx201 is safe and improves biomarkers of skin barrier function and suppresses biomarkers of AD-associated inflammation across multiple T helper cell pathways.