The NIF mouse spontaneously develops chronic inflammation and fibrosis in the liver and kidney. Histopathological and comparative transcriptomic analyses of the liver and kidney have revealed a large similarity with human sterile liver fibrosis and renal fibrosis, respectively.
Inficure and CymaBay performed a functional study in the NIF mouse model using seladelpar, a selective peroxisome proliferator (PPAR) delta agonist currently in a pivotal 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 positive data presented at the American Association for the study of Liver Diseases (AASLD) by Inficure and CymaBay Therapeutics demonstrated not only a fibrosis reducing effect observed in other animal models but that fibrosis reduction will also occur in the kidney. 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.
InfiCure Bio has developed a faster and more accurate way for pharmaceutical companies that want to test the efficiency of new drugs that treat fibrosis. Fibrosis, or scar tissue, is the body’s natural way of repairing damaged and inflamed tissue. If, however, this process continues unchecked, large amounts of fibrosis can accumulate in the tissue and the organ’s function becomes compromised.
”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.
Ed further comments on the successful treatment in the NIF mouse: “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.”
You can find the poster at: https://content.equisolve.net/cymabay/media/3619e05c8ce63c734b2342e7d1f066ff.pdf
For more information:
Sofia Mayans, PhD, CEO Inficure Bio
+46 70-366 46 66
About Inficure Bio
Inficure Bio is a life science company focused on preclinical development of drugs for treatment of chronic inflammatory and fibrotic conditions. The company has a panel of preclinical models, including a unique model, for studies of chronic inflammation and fibrosis.
Inficure Bio is based on extensive expertise in immunology, inflammation and fibrosis and offers a competent and flexible service in this area. Inficure Bio operates in a global market with customers in e.g. Australia, US and Europe. Further information about the company can be found at www.inficurebio.com.