On September 25, 2016 Leading oncology biopharmaceutical company BerGenBio AS, reported important new preclinical study data on its first-in-class AXL inhibitor, BGB324 (Press release, BerGenBio, SEP 25, 2016, View Source [SID:SID1234515416]). The study showed AXL to be a key factor in tumour resistance to the emerging class of new immune checkpoint inhibitors that can be targeted through combination therapy with BGB324. The study data was presented in a poster today at CRI-CIMT-EATI-AACR – The 2nd International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper), in New York.
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The new study evaluated whether BGB324 used in combination with immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1) in mouse carcinoma models enhanced the effect of immune checkpoint blockade in aggressive adenocarcinomas displaying limited immunogenicity. BGB324 is a highly selective small molecule inhibitor of the AXL receptor tyrosine kinase. An important regulator of the tumour cell plasticity related to EMT (Epithelial-to-Mesenchymal Transition), AXL signalling is also a key suppressor of the innate anti-tumour immune response. Thus AXL contributes uniquely to both tumour intrinsic and extrinsic mechanisms that suppress anti-tumour immunity. The new study shows that AXL was induced in tumours by immune checkpoint inhibitor treatment and postulated that this could limit their efficacy.
BGB324 is the only selective AXL inhibitor currently in clinical development. Phase Ib clinical trials are underway as single agent and in combination with standard of care drug (cytarabine) in acute myeloid leukaemia (AML), and in combination with erlotinib in non-small cell lung cancer (NSCLC).
Richard Godfrey, Chief Executive Officer of BerGenBio, commented:
"We believe this strong new preclinical data clearly demonstrates the rationale for combining BGB324 with immune checkpoint inhibitors to treat aggressive cancers. This study shows that these inhibitors actually increase AXL expression that supports immune evasion. Treatment with BGB2324 counters this, increasing tumor immunogenicity and promoting the anti-tumour response. In addition to the ongoing development of BGB324 in AML and NSCLC, this data suggests that BGB324 could also be used in combination with cancer immunotherapeutic agents to enhance their efficiency."