Performance of FXR agonist pharmacology studies using our NASH model
We would like to share with you about our experience evaluating farnesoid X receptor (FXR) agonists in the world’s first mouse model that induces liver cancer from nonalcoholic steatohepatitis (NASH) – the STAM™ model – developed by SMC Laboratories, Inc.
The nuclear receptor FXR is activated by bile acids and involved in the regulation of cholesterol metabolism, glucose metabolism and insulin sensitivity.
This is why activation of FXR is thought to lead to the treatment of NAFLD/NASH and a promising target molecule for therapeutic drugs.
Using our model, we have a lot of experience evaluating the efficacy of FXR agonists, such as Tropifexor (Novartis), EDP-305 (Enanta), and Vonafexor (ENYO Pharma), and some of those results have been published in papers and conference presentations.
［Chau M et al. International Journal of Gastroenterology. 2019.; Hernandez E et al. Hepatol Commun. 2019.; Radreau P et al. AASLD. 2019.］
Since NASH has complex and unclear pathogenic mechanisms, no animal model has been reported that can completely reproduce the human phenotype.
Therefore, it is necessary to assess efficacy for NASH using multiple animal models such as genetically engineered models, diet-induced models, and chemical-induced models.
In fact, two candidates mentioned above, Tropifexor and EDP-305, were also tested in other NASH models such as the CDAHFD and Amylin models, in addition to our original NASH model.
This NASH model is one of the few animal models in which both the NAFLD activity score and fibrosis positive area can be assessed, which are the primary endpoints in NASH clinical trials, because it shows similar histological pattern to human NASH.
We have conducted over 800 contract pharmacology studies using this NASH model, and have broad experience evaluating the efficacy of a wide variety of molecular target compounds besides FXR agonists.
Utilizing our experience and the specialist knowledge, we work closely with clients to design tailored studies based on the mechanism of action of your test substance, and provide clients with the data that can translate to results in clinical trials.