Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition with recurrent painful nodules, abscesses, and sinus tract formation leading to irreversible tissue damage and scarring. Previous transcriptome analyses have identified markers that are significantly elevated in lesional HS skin, including cytokines (interleukin [IL]-1α, IL-6, tumor necrosis factor [TNF]-α, IL-17, IL-12/23, IL-10), interferon family members, Toll-like receptor 2, antimicrobial peptides, and tyrosine kinases (Janus kinase [JAK] 1/3, BTK, SYK) and their downstream signaling partners. Here we generated and studied skin punch biopsy transcriptomic and blood proteomic data from patients (pts) with HS enrolled in 2 trials (NCT03569371, NCT03607487) evaluating INCB054707, an oral small-molecule JAK1-selective inhibitor, for 8 weeks (wk). Available paired biopsies were evaluated by RNA sequencing (RNA-Seq) comparing lesional skin at baseline and Wk 8 from pts receiving INCB054707 15 or 30 mg once daily (QD); blood samples were collected at baseline and Wk 4 and 8 from all INCB054707 (15, 30, 60, and 90 mg QD) and placebo groups. Following treatment, RNA-Seq analyses showed downregulation of many HS disease markers and inflammatory signaling pathways, elevation of several genes involved in normal sweat gland biology, and reversal of a gene expression signature shared by HS lesional and wounded skin in the 30-mg QD group at Wk 8. Sera proteomic data evaluating >1100 proteins (Olink Proteomics platform) revealed that JAK1 inhibition with INCB054707 was associated with dose-dependent reductions in specific proteins at Wk 4 and 8. Several proteins that exhibited reduced levels in circulation were also identified as being elevated in HS lesional vs healthy skin, such as TNF, IL1R1, IL2RA, ADAM8, and S100A12. These results show the association of INCB054707 treatment with improved disease biology in pts with HS.

ESDR049 - Janus Kinase 1 Inhibitor INCB054707 Modulates Disease-Associated Markers and Pathways in Hidradenitis Suppurativa

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING