Innovative drugs for aggressive, drug resistant cancers
BerGenBio AS is a biopharmaceutical company committed to developing novel cancer therapeutics that can prevent or reverse acquired drug resistance by inhibiting a pathway known as epithelial to mesenchymal transition (EMT). Its lead drug candidate, BGB324 is the only selective Axl kinase inhibitor in clinical development. Axl kinase is an essential mediator of EMT and acquired drug resistance in many tumour types, including lung, breast, prostate as well as certain leukemias. The Company has developed a pipeline of drug candidates targeting the EMT process for cancer and other diseases. It’s second program, BGB002, which inhibits a novel, undisclosed target of EMT, has received a highly prestigious scientific award and funding in 2014 for development to formal preclinical studies.
Our approach to cancer
Cancer is one of the leading causes of death worldwide. While the detection and treatment of primary tumours has improved significantly in recent years, frequently these cancers recur as secondary, metastatic tumors and tend to be very aggressive and drug resistance, causing most cancer-related fatalities. Effective diagnostic and therapeutic options for such aggressive cancers remain a significant unmet medical need. Understanding how tumors become invasive (metastatic) and resist current treatments is a major health issue. BerGenBio is a leader in understanding EMT biology in cancer, which mediates the biological drivers of aggressive, drug resistant cancers, and is committed to discovering and developing novel drugs targeting EMT. It discovers EMT targets through its proprietary, patent protected, technology platform, CellSelect™, which utilises a high content RNAi based screen to identify and validate novel targets and biomarkers. The Company has identified a number of novel EMT targets using CellSelect™, including Axl kinase, and is developing a pipeline of innovative drug candidates against these. BGB324, which targets Axl, will be thoroughly evaluated in several multi-centre clinical trials, for non-small cell lung cancer and acute myeloid leukaemia patients.
BerGenBio is developing a pipeline of novel therapeutics that inhibit EMT, a pathway that drives emergence of an aggressive phenotype of cancer that is associated with metastases, acquired drug resistance and thus poor prognosis.
Axl kinase is key in driving cancer drug resistance
BerGenBio was first to discover that Axl tyrosine kinase receptor is an essential mediator of EMT. Axl is upregulated in tumors residing in a hostile micro-environment and mediates the EMT process by signal transduction to the nucleus of the cancer cells, which in turn drives escape (metastasis) and acquired drug-resistance in many cancers. BGB324, which is an orally bioavailable small molecule, potently and selectively inhibits Axl kinase and has shown significant anti-tumour activity in many preclinical in vivo cancer models, including lung cancer, pancreatic cancer and certain leukemias. In these in-vivo studies, BGB324 was shown to delay or reverse acquired drug resistance when used in combination with standard of care therapy, including cytotoxic and targeted therapies.
The hostile tumour microenvironment induces EMT, which drives the cancer cells to develop a more invasive and drug resistant phenotype, Axl kinase is an essential mediator of the EMT process.