On April 2, 2019 BerGenBio ASA (OSE: BGBIO) a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for multiple cancer indications, reported its preclinical data strengthening bemcentinib’s broad potential in reversing tumour-mediated immunosuppression and therapy resistance, presented by the Company’s academic collaborators at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 (March 29 – April 3, Atlanta, Georgia) (Press release, BerGenBio, APR 2, 2019, View Source [SID1234534952]).
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Leading academic groups from the Gustave Roussy Cancer Centre in Paris, France, MD Anderson Cancer Center in Houston, TX, and UT Southwestern Medical Center in Dallas, TX, presented three posters describing pre-clinical findings generated in collaboration with BerGenBio on AXL’s role in aggressive cancer and bemcentinib’s therapeutic effect. The data presented lend further support to the Company’s ongoing clinical proof-of-concept programme and planned late stage strategy evaluating bemcentinib’s potential as a monotherapy and in combination across several indications.
A summary of results presented is given below.
(1) Salem Chouaib et al, Gustave Roussy Cancer Centre, Paris, France: AXL targeting enhances lymphocyte-mediated cytotoxicity of lung cancer cells. Abstract – 1200
Summary of results presented:
NSCLC cells expressing AXL were less prone to cell lysis mediated by cytotoxic T-lymphocytes (CTL) or NK-cells
Bemcentinib treatment led to increased CTL and NK-cell mediated killing of these AXL expressing NSCLC cells
(2) Kavya Ramkumar et al, The University of Texas, MD Anderson Cancer Center, Houston, TX: Targeting AXL sensitizes non-small cell lung cancer to ATR inhibitors by enhancing replication stress. Abstract – 276
Summary of results presented:
Bemcentinib treatment induces DNA damage and a subsequent DNA-damage response in NSCLC cells in a dose-dependent manner
Bemcentinib acts synergistically with DNA-damage-repair targeting agents (ATR inhibitors VX-970 or AZD6738) in reducing viability of NSCLC cells
(3) Wenting Du et al, The University of Texas Southwestern Medical Center, Dallas, TX: AXL is critical for pancreatic cancer progression and metastasis. Abstract –1037
Summary of results presented:
Downregulation of AXL via genetic engineering of pancreatic tumour models resulted in a more active immune microenvironment, prolonged survival and improved response to gemcitabine
Pharmacological intervention with bemcentinib similarly achieves immune activation and potentiates the effect of gemcitabine in pancreatic models where AXL is present on tumour and stroma cells
About AXL
AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases. In cancer, AXL suppresses the body’s immune response to tumours and drives cancer treatment failure across many indications. AXL inhibitors, therefore, have potential high value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases.
About Bemcentinib
Bemcentinib (formerly known as BGB324), is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development programme. Ongoing clinical trials are investigating bemcentinib in multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent.Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity. Increase in AXL function has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers.