Soquelitinib, a selective ITK inhibitor, demonstrates activity in atopic dermatitis (AD) phase 1 clinical trial by a novel mechanism of action

Summary: Abstract Body: Interleukin-2-inducible T cell kinase (ITK) is required for the differentiation of naïve helper T cells (Th) into Th2 and Th17 subsets. Given the critical role of these cells in AD, we are evaluating soquelitinib (SQL), an oral, covalent selective ITK inhibitor shown to block Th2 and Th17 differentiation and the production of their associated cytokines such as IL-4, 5, 13, 31, 17, for the treatment of AD. We report interim results of a Phase 1 study evaluating SQL’s safety and preliminary efficacy in patients (pts) with moderate to severe AD. The randomized, double blind study design is: 4 cohorts (sequentially enrolled) of 16 pts (12 active to 4 placebo [PBO]); 4 week treatment with additional 30 day follow-up; dosages from 100mg BID, 200mg QD, 200mg BID, to 400mg QD. The 100mg BID and 200mg QD cohorts are fully enrolled. SQL-treated pts demonstrated disease response vs PBO at either dose in terms of mean %EASI reduction at Day 28. EASI 75 or IGA 0/1 was achieved in 25% of pts at 100mg BID dose and in 57% at 200mg QD dose. No PBO pts achieved either measure of response. Serum cytokines including IL-5, 17F, 31, 33 and TSLP were reduced more from baseline to Day 28 in treated responders vs non-responders (p≤0.02 for each comparison) while PBO pts showed little change in these cytokines. Day 58 safety follow-up showed continued improvement in EASI in the “off period” for SQL-treated pts but not in PBO. Increased circulating FoxP3 +Tregs were found in the blood of SQL treated pts and a reduction in circulating (type 2 innate lymphoid cells) ILC2 cells were seen. In SQL-treated pts, AEs were limited to 1 Gr 1 nausea and 1 Covid 19; all pts received the full course of treatment. This is the first report of selective ITK inhibition for treatment of AD and indicates that this mechanism has the potential for more durable control of AD with an oral agent due to blockade of multiple Th2/Th17 cytokines, induction of Treg suppression and blockade of ILC2. Albert S. Chiou¹, James T. Rosenbaum², Lih-Yun Hsu², Dan Li², Gabriel Luciano², Suresh Mahabhashyam², Richard Miller² 1. Stanford Medical Center, Palo Alto, CA, United States. 2. Corvus Pharmaceuticals Inc, So. San Francisco, CA, United States. Clinical Research: Interventional Research