Ascletis Announces Completion of the Bridging Study and Initiation of Phase II Trial of FXR Agonist ASC42 in China for Chronic Hepatitis B Indication

--ASC42 bridging study demonstrated consistent pharmacokinetic profiles between U.S. and Chinese population

-- ASC42 was safe and well tolerated in Chinese population with only grade 1 adverse events

--10 mg and 15 mg once daily doses of ASC42 were selected in combination with pegylated interferon and nucleos(t)ide analogs for Phase II study in patients with chronic hepatitis B

 

Hangzhou and Shaoxing, China, August 25, 2021-- Ascletis Pharma Inc. (HKEX: 1672) announces today the completion of the bridging study and initiation of Phase II trial of farnesoid X receptor (FXR) agonist ASC42 in China for chronic hepatitis B (CHB) indication. ASC42 is an in-house developed, novel non-steroidal, selective, potent FXR agonist with best-in-class potential.


CHB is the second indication of ASC42. As an FXR agonist, ASC42 has a 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 hepatitis B surface antigen (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 HBsAg and HBV pregenomic RNA (pgRNA), indicating that ASC42 has therapeutic potential to functionally cure CHB.


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 was no pruritus observed and no treatment-emergent alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations during 14-day, once daily treatment with 15 mg (therapeutic dose). 

(Details referring to press release:https://www.ascletis.com/news_detail/175/id/507.html)


Based on the pharmacokinetic data from the ASC42 Phase I trial in the U.S. (ClinicalTrials.gov Identifier: NCT04679129), the bridging study in China was a randomized, placebo-controlled, double-blind single-ascending dose study in 30 healthy subjects receiving ASC42 or matching placebo (ClinicalTrials.gov Identifier: NCT04965337). The objective of the bridging study was to select doses for the upcoming Phase II trial in China in patients with CHB. ASC42 bridging study demonstrated consistent pharmacokinetic profiles between the U.S. and Chinese population. Furthermore, ASC42 was safe and well tolerated in Chinese population and had only grade 1 adverse events (AEs), with no grade 2 or above AEs, no serious adverse events (SAEs) or premature discontinuations.


Based on Phase I study in the U.S. and bridging study in China, 10 mg and 15 mg once daily doses of ASC42 were selected in combination with pegylated interferon and nucleos(t)ides analogs for Phase II study in Chinese patients with CHB.


 “I am excited to be the principle investigator of ASC42 Phase II clinical trial for CHB indication,” said Professor Jinlin Hou, MD, Principal Investigator of ASC42 Phase II Study for CHB indication, Director of the Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, “As the functional cure is becoming so important in CHB management, ASC42, a potential best-in-class FXR agonist, offers a novel mechanism of action for us to defeat CHB.”


“We are thrilled about having advanced FXR agonist ASC42 into Phase II study only 2.5 months after the IND approval in China for CHB indication.” said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis, “This demonstrates again the execution excellence and dedication of our clinical development team.”


While promoting Pegasys® (pegylated interferon) that Ascletis is also developing breakthrough therapies, including ASC22 (subcutaneous PD-L1 antibody, Phase IIb trial ongoing in China) and ASC42. which its ultimate goal is to achieve functional cure of CHB which is still a dramatic unmet medical need.


About Ascletis

Ascletis is an innovative R&D driven biotech listed on the Hong Kong 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, and viral diseases, to address unmet medical needs both 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 a robust R&D pipeline of drug candidates.

(1) NASH: Gannex, a wholly-owned company of Ascletis, is 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 fixed-dose combinations. (2) Cancer lipid metabolism and oral checkpoint inhibitors: 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  next generation checkpoint inhibitors. (3) Viral diseases: (i) Hepatitis B: focus on breakthrough therapies for CHB functional cure with a subcutaneously-injected PD-L1 antibody – ASC22 –and Pegasys® as cornerstone drugs. (ii) Hepatitis C: successfully launched an all-oral regimen of combining ASCLEVIR® and GANOVO® (RDV/DNV regimen). (iii) HIV/AIDS: ASC22, an immune therapy to restore HIV-specific immune responses and eventually lead to a functional cure of HIV-infected patients. For more information, please visit www.ascletis.com.


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