Ascletis Received China IND Approval of Its FXR Agonist ASC42 for Chronic Hepatitis B Indication

Ascletis Pharma Inc. today announces that China National Medical Products Administration (NMPA) has approved the Investigational New Drug (IND) application for its drug candidate ASC42 to conduct clinical trials for chronic hepatitis B (CHB) indication.

ASC42 is an in-house developed, selective, potent farnesoid X receptor (FXR) agonist. ASC42 is an oral tablet formulation developed with in-house proprietary technology and is stable at room temperature.

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.

Nucleot(s)ide analogues (direct antiviral drugs) inhibit only reverse transcription of HBV RNA into HBV DNA and do not inhibit the transcription of HBV cccDNA (covalently closed circular DNA) into HBV RNA, thus have no inhibitory effect on HBsAg. As an FXR agonist, ASC42 has unique mechanism of action against 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.

ASC42 is the second investigational new drug of Ascletis for HBV functional cure. Another investigational new drug for HBV functional cure is PD-L1 antibody ASC22, which is currently in Phase IIb study and has demonstrated good safety and preliminary efficacy in HBsAg reduction in Phase IIa study.

"We are excited about ASC42 IND approval for CHB," said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis, "This is a key milestone for our CHB functional cure pipeline. The potential synergy between ASC42 and ASC22 or Pegasys® is promising for our effort on CHB functional cure."

About Ascletis

Ascletis is an innovative R&D driven biotech, a health supply company, 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.