AXL as a therapeutic target in fibrosis; biology and biomarkers

Fibrose, økt bindevevsmengde i et vev eller organ, er en viktig årsak til sykdom og død over hele verden. Det er derfor et betydelig behov for nye behandlingsformer som kan forhindre fibrose. Bioteknologifirmaet BerGenBio ASA utvikler nye hemmere av AXL/EMT signalveien, en mekanisme som ikke bare driver legemiddelresistens og spredning (metastase) av kreft, men som også spiller en viktig rolle for utvikling av fibrose og i ulike infeksjonssykdommer som COVID19. I dette prosjektet skal BerGenBio forsøke å vise at hemming av AXL er en sikker og effektiv måte å behandle fibrose i pasienter, og å forstå mekansimene for hvordan hemming av AXL hindrer og reduserer fibrose. For å nå disse målene samarbeider vi tett med akademiske grupper som er eksperter på AXL singnalering og hvilken rolle AXL spiller for sykdomsutvikling i nyre, lever og lungefibrose. Pre-kliniske data fra dette prosjektet har blitt presentert som ePoster presentasjon ved ERA-EDTA i mai 2022 og som poster ved EASL i juni.

The project has further validated AXL as a relevant and potential target in fibrotic diseases of kidney, liver and lung, and has contributed to several of the UN Sustainability development goals. Good health and wellbeing: Through completion of a clinical Ph1a and Ph1b study, we have confirmed safety and tolerability of our proprietary anti-AXL antibody tilvestamab and determined PK and target engagement in a selected patient population. Quality education: Funding from this project has been important in the training of several PhD students both internationally in BerGenBio and at collaborating academic institutions. Industry, Innovation and Infrastructure: This project has contributed to further knowledge of the important role of AXL in fibrotic pathology in experimental models. Several model systems and assays have been developed to allow studies of inhibition of AXL using the tilvestamab monoclonal antibody and comparative studies between the small molecule AXL inhibitor bemcentinib and tilvestamab.

BerGenBio ASA is a clinical-stage oncology company advancing first-in-class, selective AXL kinase inhibitors against aggressive diseases. The receptor tyrosine kinase AXL is becoming a profiled target for developing drugs to treat resistant and metastatic cancer. Over the last decade it has become evident that the AXL pathway also plays a decisive role in fibrosis. Fibrotic diseases of the lung, liver and kidney are a significant cause of death worldwide. BerGenBio’s selective AXL inhibitors are effective in preventing fibrosis in a variety of model systems. The objective of this project is to perform research and development to demonstrate that AXL-inhibition is a safe and effective treatment for fibrosis in human patients and to deepen our understanding of the mechanisms by which AXL-inhibition prevents and reduces fibrosis. To achieve these goals, BerGenBio has established collaborations with academic groups that are experts in AXL signaling (Prof. James B Lorens, Department of Biomedicine, UoB, Bergen, Norway) and on the role of AXL signaling in liver fibrosis (PhD Albert Morales, Institute of Biomedical Research, Barcelona, Spain).