Corvus Pharmaceuticals (CRVS) Study result summary

Key clinical findings

• Phase I trial of soquelitinib in atopic dermatitis showed strong efficacy, with 75% of patients achieving EASI 75, 25% EASI 90, and 33% IGA 0/1 after eight weeks of treatment, outperforming placebo.

• Mean EASI score reduction was 72% at eight weeks for soquelitinib versus 40% for placebo, with durable responses persisting post-treatment.

• Efficacy was consistent in patients with prior systemic therapy, including those resistant to dupilumab and JAK inhibitors.

• No new safety signals or severe adverse events were observed; adverse events were mild to moderate and similar between active and placebo groups.

• Disease control was maintained in the 30-day post-treatment follow-up period.

Study design and patient population

• The study included four cohorts, with Cohort 4 using a one-to-one randomization and an eight-week treatment period, while earlier cohorts used four weeks.

• 72 patients were enrolled across all cohorts, with 48 receiving soquelitinib and 24 placebo; 35% had received prior systemic therapies.

• Patients had moderate to severe atopic dermatitis, often with advanced disease and prior treatment failures.

• Placebo-controlled, blinded design ensured robust efficacy assessment, with no concomitant topical steroids allowed.

• Cohort 4 had well-balanced arms and included 50% of patients with prior systemic therapy.

Mechanism of action and biomarker insights

• Soquelitinib is a selective, oral ITK inhibitor, sparing RLK and minimizing off-target effects, designed to regulate multiple T cell pathways.

• ITK inhibition reduces Th2 and Th17 cell differentiation and cytokine production, while increasing Treg cells, supporting immune rebalancing.

• Biomarker analysis showed sustained reductions in IL-4, IL-5, IL-17, TARC, and Th2 cells, with effects persisting beyond treatment.

• Dose-dependent biomarker responses were observed, with the largest reductions in higher dose cohorts.

• Single-cell RNA-seq confirmed reduction in Th2 cells and changes in JAK-STAT signaling pathways.