Ascletis Announces Dosing of the First Cohort of Healthy Subjects in the FXR Agonist ASC42 Bridging Study for Chronic Hepatitis B Indication in China

Ascletis Pharma Inc. today announces the dosing of the first cohort of healthy subjects in the ASC42 bridging study in China for CHB indication. ASC42 is an in-house developed, novel non-steroidal, selective, potent FXR agonist with best-in-class potential.

On June 7, 2021, Ascletis announced that China National Medical Products Administration (NMPA) had approved the Investigational New Drug (IND) application for ASC42 to conduct clinical trials in China for CHB indication. 

On June 16, 2021, Gannex, a wholly owned company of Ascletis announced ASC42 positive topline results of safety and pharmacodynamic biomarkers from the U.S. Phase I trial of NASH indication. The data indicated that there were no pruritus observed during 14-day treatment of the once-daily human therapeutic dose of 15 mg and no treatment-emergent alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations during 14-day, once daily treatment with 15 mg. 

Based on the pharmacokinetic data from the ASC42 Phase I trial in 64 healthy subjects in the U.S., the bridging study in China is a randomized, placebo-controlled, double-blind single-ascending dose (5 mg and 15 mg) study in 30 healthy subjects receiving ASC42 or matching placebo (ClinicalTrials.gov Identifier: NCT04679129). The objective of the bridging study is to select doses for the upcoming Phase II trial in China in patients with CHB.

As an FXR agonist, ASC42 has unique mechanism of action against hepatitis B virus (HBV): ASC42 inhibits the transcription of HBV cccDNA into HBV RNA, which in turn inhibits the translation of HBV RNA into HBsAg. ASC42 may also reduce HBV cccDNA stability. Both in vitro primary human hepatocyte (PHH) cells and in vivo AAV/HBV mouse studies demonstrated that ASC42 significantly inhibited serum hepatitis B surface antigen (HBsAg) and HBV pregenomic RNA (pgRNA), indicating that ASC42 has therapeutic potential to functionally cure CHB.

"We are excited about moving FXR agonist ASC42 into CHB indication," said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis, "Dosing the first cohort subjects in China for CHB indication is achieved merely one month after receiving China NMPA's IND approval. This demonstrates again the execution excellence of our clinical development team."

About Ascletis

Ascletis is an innovative R&D driven biotech and listed on Hong Kong, S.A.R., China Stock Exchange (1672.HK). Ascletis is committed to developing and commercializing innovative drugs in the areas of NASH, cancer lipid metabolism and oral checkpoint inhibitors, viral hepatitis and HIV/AIDS for unmet medical needs in China and globally. Led by a management team with deep expertise and a proven track record, Ascletis has developed into a fully integrated platform covering the entire value chain from discovery and development to manufacturing and commercialization.

Ascletis has three marketed products and seventeen R&D pipeline drug candidates or combination therapies (eleven of them developed in-house). 1. NASH: Gannex, a wholly-owned company of Ascletis, is fully dedicated to the R&D and commercialization of new drugs in the field of NASH. Gannex has three clinical stage drug candidates against three different targets – FASN, THR-beta and FXR, and three combination therapies. 2. Cancer lipid metabolism and oral checkpoint inhibitors: focus on a pipeline of oral inhibitors targeting FASN which plays a key role in cancer lipid metabolism and a pipeline of oral PD-L1 small molecule inhibitors as the next generation checkpoint inhibitors. 3. Viral hepatitis: (i) Hepatitis B: focus on breakthrough therapies for HBV clinical cure with subcutaneously injected PD-L1 antibody - ASC22 and Pegasys® as cornerstone drugs. (ii) Hepatitis C: successfully launched all oral regimen of ASCLEVIR® and GANOVO® combination (RDV/DNV regimen); and ASC18 fixed dose combination (FDC) is an upgraded version of RDV/DNV regimen with bridging study finished. 4. HIV/AIDS: ASC09F is a FDC treatment of HIV targeting protease. The clinical trial application of ASC09F has been approved.