Q702 is an orally available, selective Axl/Mer/CSF1R triple kinase inhibitor showing significant anti-tumor activities through immune activation and chemo-sensitizing effects in various tumor models.Axl and Mer receptor tyrosine kinase (RTK) have been reported as playing important roles in multiple cancer indications. Axl has been known to promote epithelial-to-mesenchymal transition (EMT) leading to drug and immune resistant tumor. Axl and Mer’s roles in inactivation of innate immunity in cancer and enveloped viral infection also have been reported. Therefore, inhibition of Axl and Mer functions has been considered as one of the good mode of actions in fighting against cancer, particularly after emergence of T cell checkpoint inhibitor therapy as Axl and Mer affects complementary innate immune system.
Colony Stimulating factor-1 receptor (CSF1R) also indicated in regulation of tumor micro-environment (TME), creating immune suppressive condition by differentiation of tumor associated macrophage (TAM) and recruitment of myeloid derived suppressor cells (MDSC). Therefore, inhibition of CSF1R functions also has been considered as effective way to activate anti-tumor immunity.
Q702 selectively inhibits Axl, Mer and CSF1R RTK at the same time, maximizing innate immune activation capacity as well as making cancer cells more drug and immune susceptible. Q702 is effective as monotherapy as well as in combination with T cell checkpoint inhibitors in various tumor models. Monotherapy activity of agents with innate immune activating mode of action has been increasingly regarded as an essential characteristic for success in clinic due to recent set-backs of leading drug candidates in the area. Q702 builds up anti-tumor immunity through multiple mode of actions, it is well positioned to be effective in severely immune suppressed conditions.
Q702 is under preclinical development and gearing up to file U.S. IND in 2019 against solid tumors.
1. Q701, a selective Axl/Mer inhibitor as an immune checkpoint inhibitor (2017 AACR-NCI-EORTC poster)
2. Q702, Selective Axl, Mer and CSF1R triple kinase inhibitor with dual potentials leading to tumor regression (2019 AACR annual meeting)
1. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature, 507(7493),508-12, 2014; (Mar, 27) (Pubmed)
1. Killer targets in metastasis (SciBX)