Gyre Therapeutics, Inc. announced the publication of the manuscript titled Hydronidone induces apoptosis in activated hepatic stellate cells through endoplasmic reticulum stress-associated mitochondrial apoptotic pathway in the Journal of Gastroenterology and Hepatology. This publication includes both in vivo and in vitro studies supporting the potential of hydronidone (F351), a novel derivate of pirfenidone, as a promising therapy for the treatment of liver fibrosis. Liver fibrosis is characterized by the progressive accumulation of extracellular matrix (ECM), which disrupts the normal liver architecture.

Research has shown that quiescent HSCs undergo activation and transform into myofibroblast-like cells to produce ECM in chronic liver disease, and therefore that liver fibrosis can be reversed by eliminating aHSCs. This study found that treatment with hydronidone significantly promoted apoptosis in aHSCs in both the CCl4- and DDC-induced liver fibrosis in mice and LX-2 cells. Mechanistic studies revealed that hydronidone triggered ERS and subsequently activated the IRE1a-ASK1-JNK pathway and subsequent dysfunction of the mitochondria, ultimately resulting in the apoptosis of aHSCs.

Gyre Pharmaceuticals is currently evaluating hydronidone in a Phase 3 trial for the treatment of Chronic Hepatitis B (CHB)-associated liver fibrosis in the PRC with topline data anticipated by early 2025. The trial is evaluating 248 patients with a primary endpoint of the reduction of the liver fibrosis score (Ishak Scoring System) by at least one grade after taking hydronidone in combination with entecavir. Pending results from the Phase 3 trial, Gyre intends to initiate a Phase 2 a proof-of-concept trial to evaluate hydronidone for the treatment of NASH-associated liver fibrosis in 2025.