Corvus Pharmaceuticals (CRVS) announced new preclinical data highlighting the potential of soquelitinib, the Company’s lead ITK inhibitor program, to prevent lung damage, inflammation and pulmonary hypertension caused by systemic sclerosis. Systemic sclerosis is an autoimmune disease characterized by inflammation, fibrosis, vascular damage and interstitial lung disease, with ILD and pulmonary hypertension being the major causes of death in these patients. The disease involves the activation of Th2 helper T cells and cytokines produced by these cells, including IL-4, IL-5 and IL-13. The researchers utilized a Fra-2 transgenic mouse model that encompasses many of the features of systemic sclerosis in humans, including spontaneous systemic inflammation and fibrosis in the lungs, skin and heart, which leads to pulmonary hypertension and ILD. These mice also exhibit an accumulation of Th2 helper T cells. The Fra-2 transgenenic mice were treated with oral soquelitinib for seven weeks, compared to control Fra-2 transgenic mice. Compared to the control, the mice treated with soquelitinib showed: Significant reduction in lung infiltration and fibrosis, assessed by histology; Significant improvement in clinical score, which measures disease severity; Reduced vascular smooth muscle hypertrophy, assessed by histology; Reduced right ventricular systolic blood pressure, consistent with improvement in pulmonary hypertension. These results were confirmed in a second model of pulmonary fibrosis using a bleomycin lung injury model. Treatment with soquelitinib showed reduced pulmonary fibrosis, and infiltration with Th2 helper T cells.
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