Researchers published the findings in the American Journal of Respiratory and Critical Care Medicine. The article is titled “Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis.” The results were also presented at the 53rd annual meeting of the European Association for the Study of the Liver in Paris, April 11-15.
Bemcentinib combats tissue scarring, or fibrosis, by inhibiting a protein called Axl receptor tyrosine kinase. It is associated with various cancers, and its activity is increased in idiopathic pulmonary fibrosis (IPF).
Researchers at Cedars-Sinai Medical Center in Los Angeles discovered that Axl levels were higher in lung tissue with IPF than in normal cells.
The team also showed that bemcentinib prevented cells that contribute to fibrosis development, called fibroblasts, from proliferating and traveling elsewhere in the lungs. This stopped the development of fibrosis, according to their laboratory and mouse model research.
Based on these results, the team suggested that Axl “contributes to the activation of pulmonary fibroblasts in IPF, suggesting that targeting this RTK [receptor tyrosine kinase] pathway might be an effective anti-fibrotic strategy.”
The team added that Axl levels could be used as a biomarker to identify patients with poor disease outlooks or who might not respond well to treatment with an Axl inhibitor.
“This patient data and preclinical findings in IPF and cirrhotic NASH [nonalcoholic steatohepatitis, a condition characterized by liver fibrosis] are very compelling and suggest that selective AXL inhibition may have potential as a new approach to treating life-threatening fibrotic diseases,” Richard Godfrey, chief executive officer of BerGenBio, said in a press release.
“While our focus remains clearly on completing our Phase 2 clinical program with bemcentinib and to establish proof of concept for its role as a cornerstone of cancer therapy, we are intrigued by the possibility of therapeutic benefit from our AXL inhibitors in fibrotic diseases. We will continue to support this research and look forward to integrating it into our pipeline development strategies,” Godfrey added.
Bemcentinib is also being investigated as a cancer treatment. A Phase 1/2 clinical trial (NCT02424617) is evaluating it in combination with erlotinib as a treatment for patients with Stage 3b or Stage 4 non-small cell lung cancer.