Mice are treated with Sotuletinib hydrochloride or vehicle, and evaluated for symptom-free survival. Median survival in the vehicle-treated cohort is 5.7 weeks. In striking contrast, Sotuletinib hydrochloride significantly improves long-term survival with 64.3% surviving to the 26-week trial endpoint. This endpoint is chosen because Ink4a/Arf / mice develop spontaneous tumors, including lymphomas and sarcomas, beginning at ~30 weeks. Sotuletinib hydrochloride is well-tolerated over long-term treatment, with no visible side-effects, consistent with histopathological studies. Histological grading revealed high-grade, invasive gliomas in all vehicle-treated mice. By contrast, Sotuletinib hydrochloride-treated animals have significantly less-malignant tumors, and no detectable lesions in 55.6% of asymptomatic mice at the endpoint[1]. Mice receiving Sotuletinib hydrochloride shows reduced CSF1R staining in both cervical tumors and the associated stroma, with a significant decrease in CSF1R+ stromal macrophages relative to vehicle-treated mice (P<0.05)[2].
