BerGenBio ASA announced that it presented data linking AXL activation to STK11 loss of function in Non-Small Cell Lung Cancer (NSCLC) in an abstract titled, AXL as a Therapeutic Target in STK11 mutant NSCLC, at the American Association for Cancer Research (AACR) Annual Meeting 2023. An analysis of tumors lacking STK11 function from BerGenBio's 2nd line NSCLC trial (BGBC008) and publicly available datasets suggest that STK11 and KEAP1 mutations are transcriptionally similar and share a common signature for STK11 loss of function. Loss of function leading to inactivation of STK11 is found in approximately 30% of lung adenocarcinomas as a result of both mutational and non-mutational mechanisms. These tumors with inactivated STK11 are likely to promote AXL activation due to high levels of energetic and metabolic stress, resulting in a poorer prognosis in NSCLC.

AXL, a member of the TAM family of receptor tyrosine kinases, is expressed in over 80% of NSCLC tumors that demonstrate loss of STK11 function. AXL is activated in response to inflammation, hypoxia, cellular stress or drug treatment. AXL is expressed in both tumor cells, where it enhances survival and drug resistance, and in innate immune cells, such as dendritic cells and macrophages, where AXL drives immune suppression.

BerGenBio's selective AXL inhibitor bemcentinib targets key survival and resistance mechanisms within the tumor and restores the anti-tumor characteristics of innate immune cells within the tumor microenvironment.