Incyte is developing a small molecule inhibitor of AXL and MER.
AXL and MER belong to the TAM family of receptor tyrosine kinases (RTKs), broadly expressed in a variety of tissues. AXL and MER are overexpressed, amplified, and/or translocated in many solid tumors and hematological malignancies.
The aberrant activation of these RTKs plays important roles in tumor growth, survival, angiogenesis, metastasis, and chemoresistance.
In addition, the tumor microenvironment can subvert the functions of AXL and MER to evade immune responses through a number of mechanisms, such as by enhancing clearance of apoptotic material, shifting tumor-associated macrophage differentiation toward an immunosuppressive phenotype, curtailing antigen-presenting cell activity, and disabling the anti-metastatic functions of natural killer cells.
The therapeutic inhibition of AXL and MER signaling may have direct anti-tumor effects while also promoting host immune responses against tumors.