Corvus Pharmaceuticals, Inc. announced the publication of preclinical data that demonstrated the potential of ITK inhibition as a novel approach to treat T cell-mediated inflammatory and immune diseases. Corvus? ITK inhibitors include soquelitinib (formerly known as CPI-818), which was used in the preclinical studies and is currently in clinical trials for oncology indications, and several next-generation molecules that are being optimized for use in a variety of inflammatory and immune disease indications.

Key results from the preclinical studies described in the publication demonstrated that soquelitinib had the following observed effects in models of inflammatory disease: Acute and chronic asthma models: Significant reductions in Th2 cytokines IL-4, IL-5 and IL-13 in both models, along with reductions in a validated disease activity score. Reduction in IL-6 signifying amelioration of inflammation. Systemic sclerosis (Fra2 gene overexpression) model: Improvement in clinical score and preservation of body weight; Improvement in lung histology, reduction of fibrosis and improvement in pulmonary vascular hypertension; Reduction of GATA3-expressing T cells, indicative of effect on Th2 cells; Reduction of ROR gammaT cells (ROR?T), indicative of effects on Th17 cells.

Pulmonary fibrosis (bleomycin-induced) model: More consistent reduction of pulmonary fibrosis compared to an FDA-approved medication (nintedanib); Similar reduction in GATA3 as the systemic sclerosis model results; Reduction in MMP2 and TGF beta, two messenger RNAs associated with fibrosis. Psoriasis (imiquimod (IMQ)-induced) model: Improvement in epidermal thickness, erosion and inflammation; In vitro studies demonstrated a reduction in the expression of ROR?T protein, a master transcription factor that is responsible for developing Th17 cells, and a corresponding dose-dependent reduction in IL-17 cytokine production. Graft versus host disease (GVHD) model: Improvement in survival rates and corresponding decrease in clinical GVHD score; No impact on engraftment or graft-versus-tumor effect.