Gannex Pharma Announces New Dual Targeting Drug for NASH

NASH- nonalcoholic steatohepatitis, an aggressive version of the fatty liver disease, is a disorder characterized by fat build-up and inflammation in the liver. It is usually non-symptomatic and may progress to cirrhosis and liver failure, similar to the damage caused by excessive alcohol consumption. 

Gannex Pharma announced a new candidate ASC43F which successfully completed Phase 1 clinical trials. ASC43F is an in-house dual-targeting oral tablet for treatment of NASH. It acts as an agonist for thyroid hormone receptor ß (THRß) and farnesoid X receptor (FXR), specifically in the liver. Activating these receptors regulates fat metabolism and induces anti-inflammatory response. 

Novel Combinatorial Therapy for NASH

ASC43F is a fixed dose combination of two candidates ASC41F and ASC42 which were well tolerated and reduced cholesterol in participants in Phase 1 trials in the U.S and China. Rat NASH model studies demonstrated that combining the two drugs improved outcomes. ASC43F was approved in October 2021 by the U.S FDA as an IND (Investigational New Drug). 

The clinical trial was completed in 2 months after IND approval and shows promising results for Gannex’s NASH pipeline. Established in 2019, Gannex Pharma works on research and commercialization of drugs for NASH and is a subsidiary of China-based Ascletis Pharma Inc. Currently, Gannex has 3 clinical candidates and 3 combination therapies in development. 

In phase 1 clinical trials, ASC43F was well-tolerated and safe in healthy participants and NASH patients. The pharmacokinetic data was similar to those of ASC41 and ASC42. Dr. Handan He, Chief Scientific Officer of Ascletis, explained how ASC43F functions better than monotherapy of ASC41/42. He said, “The U.S. Phase 1 study confirmed a favorable safety profile of ASC43F and similar PK parameters of ASC41 and ASC42 from ASC43F as compared to those of ASC41 and ASC42 single tablets. ASC41 and ASC42 have complementary MOA’s, as THRβ agonists have shown primarily anti-metabolic effects, while FXR agonists have shown primarily anti-fibrotic, as well as anti-inflammatory effects. Thus, a combination of these two molecules can potentially work synergistically, targeting all NASH components – steatosis, ballooning, inflammation and fibrosis. In addition, a THRβ agonist combined with an FXR agonist may reduce potential adverse events, such as lowering atherogenic risks, by decreasing the elevated LDL-C that has been associated with other FXR agonists.”

NASH – An Emerging Market for Novel Therapeutics 

With obesity rates increasing steadily across developing and developed economies, there is a large unmet need for medical interventions for fatty liver and associated disorders. Cases of NASH progression to end stage liver disease are expected to increase 2-3 fold by 2030. Despite high prevalence, currently there are no FDA-approved drugs for NASH and hence it is an attractive avenue for biopharma to invest in treatments. According to an industry report, there are currently over 140 candidates in the NASH market pipeline, under various stages of clinical review. Combination therapies are an attractive paradigm to provide solutions to patients, since NASH is mostly associated with other risk factors. 

Author

Sahana Shankar