Together with CymaBay Therapeutics Inficure Bio have co-presented positive data at the American Association for the study of Liver Diseases (AASLD).
Inficure and CymaBay performed a functional study in the NIF mouse model using seladelpar, a selective peroxisome proliferator (PPAR) delta agonist currently in a Phase 3 study for Primary Biliary Cholangitis (PBC). The goal of the study was to assess the ability of seladelpar to reduce established fibrosis in the liver in the NIF mouse model. Previous work with seladelpar supports that it may reduce fibrosis in both preclinical models and in humans. The molecular mechanisms of fibrosis reduction are not well elucidated although a reduction in established fibrosis is generally agreed to be beneficial to a patient.
The data demonstrated not only a fibrosis reducing effect observed in other animal models but that fibrosis reduction will also occur in the kidney, states the company. This gives a proof-of-concept that the NIF mouse can be used to test the effect of compounds on fibrosis in both liver and kidney at the same time.
“We are very pleased with the results from this study. Liver fibrosis and renal fibrosis are both difficult conditions for a patient, and having a model that is capable of recapitulating some of the same effects observed in humans is a key asset in drug discovery and development. These data demonstrate the utility of the NIF mouse to test various agents for their effects on fibrosis and provide insights into mechanisms that could be translated for patients benefit,” says Sofia Mayans, CEO at Inficure Bio.
”We chose to test the effect of seladelpar in the NIF mouse, since we wanted to assess if seladelpar could reduce established fibrosis. The NIF mouse has previously been used with the “reducing established fibrosis paradigm” and the model has renal fibrosis in addition to liver fibrosis. This gave us an opportunity to assess the ability of seladelpar to reduce established fibrosis in both the liver and the kidney at the same time,” says Ed Cable, Sr. Director of Research at CymaBay Therapeutics. “The data from the study reproduced the reduction of liver fibrosis observed in other models as well as the novel finding of a reduction in glomerular fibrosis, indicating that PPARdelta agonists exert beneficial extrahepatic effects. Liver fibrosis remains a feature of PBC and a compound that reduces liver fibrosis would be a significant improvement compared with the therapeutics currently available. Having access to a variety of preclinical models is key to elucidating different mechanisms underlying complex biologic processes, and the NIF mouse model provided us with a significant amount of actionable data. The NIF model, being an early developing model, provides a readily available preclinical model to test fibrosis regression in both liver and kidney.”
Photo of Team Inficure Bio