RedHill Biopharma is evaluating the potential of its proprietary therapy RHB-107 (upamostat, formerly known as Mesupron) to treat inflammatory digestive diseases and cancer, the company announced in a press release.
Results of experimental studies show that WX-UK1, the active compound in RHB-107, efficiently inhibits five serine proteases called trypsin-3, trypsin-2, trypsin-1, matriptase-1, and trypsin-6. These enzymes are associated with cancer progression and spreading, and are also important mediators of several mechanisms involved in gut homeostasis, or stablity.
These findings will be presented at the American Association for Cancer Research (AACR) 2018 Annual Meeting April 14-18 in Chicago. The study, “New potential therapeutic applications of WX-UK1, as a specific and potent inhibitor of human trypsin-like proteases,” is the result of a collaboration between RedHill and researchers at Aarhus University in Denmark.
RHB-107 was initially developed to target the serine protease urokinase (uPA), which is involved in a tissue remodeling process related to tumor invasion and spreading.
Supported by its initial anti-cancer profile, the U.S. Food and Drug Administration (FDA) granted orphan drug status to RHB-107 as a supplemental treatment for pancreatic cancer.
Results of two Phase 2 trials in advanced pancreatic cancer (NCT00499265) and in metastatic breast cancer (NCT00615940) established the therapy’s safety and tolerability profiles. Early data also suggested that RHB-107 holds therapeutic potential for both cancers when administered in combination with standard chemotherapies.
More recently, investigators re-evaluated the activity of WX-UK1. They screened about 200 human trypsin-like serine proteases the active compound could potentially target. Upon narrowing down the list of possible targets by predictive specificity, they built 3-D models of the enzymes and WX-UK1 to simulate their interaction.
Using this strategy, they identified additional enzymes that could be inhibited by WX-UK1, including trypsin-3, trypsin-2, and trypsin-1, all of which were found to be even more sensitive to WX-UK1 than the original uPA target.
Based on these findings, RedHill believes that RHB-107 could potentially treat inflammatory digestive diseases, including irritable bowel syndrome, inflammatory bowel disease, and pancreatitis.
Because it prevents trypsin-2 activity, RHB-107 may also be effective in treating inflammatory pulmonary diseases, including acute respiratory distress syndrome, acute lung injury, alpha-1 antitrypsin deficiency, and chronic obstructive pulmonary disease.