Axl and Mer receptors are reported to have many functions, including promotion of epithelial-mesenchymal transition (EMT), resistance to antitumor therap,y and negative regulation of the innate immune response. Particular attention has been given to Axl and Mer receptor tyrosine kinase's (RTK) roles in regulating macrophage and NK cell activation as tumor cells exploit Axl and Mer signaling pathway to downregulate antitumor immunity, constituting an immune checkpoint. Q701 is a highly potent, selective, orally available Axl and Mer RTK inhibitor that can relieve immune suppression through innate immunity activation leading to T-cell activation. In various syngeneic mouse models, Q701 shows tumor regression activities by treatment of compound alone or in combination with other treatments, while Q701 has no direct cytotoxic activity against tested cell lines. Q701 treatment also show immune activation profile in tumor leading to T-cell activation. Q701 is under IND-enabling studies and a back-up program with Axl, Mer, and CSF1R inhibitors is in candidate nomination stage.

Citation Format: Yeong-In Yang, Hwankyu Kang, Dongsik Park, Jiye Ahn, Jinho Choi, Seohyun Ahn, Jaeseung Kim, Kiyean Nam. Q701, a selective Axl and Mer inhibitor as an immune checkpoint inhibitor [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A205.