R&D(research and development)

F351

Drug description

Small molecule compound for liver fibrosis

Purpose of use

F351 is a new chemical entity (NCE) with global composition patent projection. It inhibits hepatic stellate cell proliferation and also the TGF-β signaling pathway. Studies in DMN and CCI4 animal models demonstrated excellent efficacy. Compared with pirfenidone, F351 has tested nearly 10 times more potent in various biochemistry, cell biology, and animal models. In photo toxicity tests, F351 also demonstrated 5-10 times improvement over pirfenidone.

Indication

Liver fibrosis is a process of scar formation on the liver which effects millions of patients in China alone. The principal cause of hepatic fibrosis/cirrhosis in Asia, including Japan and China, is viral infection hepatitis B (HBVA). In the U.S. and Europe, alcohol abuse is another leading cause of this disease. The advanced stage of liver fibrosis is liver cirrhosis. Liver transplantation is required at the advanced stage of the disease. The applicability of such transplantations is severely limited due to the finite number of donor organs available and the clinical condition of the potential recipients. Therefore development of fibrosis, and particularly cirrhosis, is associated with a significant morbidity and mortality rate. Thus, there is a critical unmet and urgent medical need to develop anti-fibrotic therapeutic strategies.

Clinical Development

The Company completed F351 Phase I A & B trials in China, with more than 200 volunteers participating in the studies. Formulated in capsule form, F351 in the studies was very well tolerated without sever adverse events observed at dosages up to 600 mg/tid. Pharmacokinetics studies demonstrated that F351 is quickly absorbed after oral administration and there is no obvious drug accumulation in human bodies. CFDA approval for Phase II trials was received in June 2014 for HBV liver fibrosis with starting dosage at 60 mg/tid (180 mg/day), and launched Phase 2 clinical trial June 2015.

For additional indications, F351 has the potential to be further developed to for Non-alcoholic steatohepatitis (NASH) liver disease and Non-alcoholic fatty liver disease (NAFLD). Other studies have indicated its ability to inhibit renal fibrosis and improve renal functions in UUO and 5/6 nephrectomy, which infers F351 may also be sued in chronic kidney failure.