Gannex Announces China NMPA Approved Phase II and III Protocols of ASC42, an FXR Agonist, for Treatment of Primary Biliary Cholangitis

Gannex Pharma Co., Ltd., a wholly owned company of Ascletis Pharma Inc. (HKEX:1672) announces today that the protocols of Phase II and III clinical trials of ASC42 to treat patients with primary biliary cholangitis (PBC) has been approved by China National Medical Products Administration (NMPA). PBC is a new chronic hepatobiliary disease indication approved for clinical trials of ASC42. The other two chronic hepatobiliary disease indications approved by China NMPA and/or U.S. Food and Drug Administration (FDA) are chronic hepatitis B (CHB) and non-alcoholic steatohepatitis (NASH).

With the approval of ASC42 PBC Phase II and III protocols by China NMPA, Gannex is expected to complete the Phase II trial in 100 patients who have an inadequate response to or are unable to tolerate Ursodeoxycholic acid (UDCA).  The Phase II study consists of three active treatment arms and one placebo control arm at the ratio of 1:1:1:1 and is expected to complete in the second half of 2022. Gannex will initiate the Phase III trial after the communications with China NMPA in terms of drug registration related matters such as Chemistry, Manufacturing and Control (CMC) and toxicology studies.

ASC42 is an in-house developed, novel non-steroidal, selective, potent Farnesoid X receptor (FXR) agonist with best-in-class potential and global intellectual property. The data from the U.S. Phase I trial of ASC42 indicated there was no pruritus observed during 14-day treatment of the once-daily human therapeutic dose of 15 mg and FXR target engagement biomarker FGF19 increased 1,780% on Day 14 of treatment with 15 mg dose. Furthermore, mean LDL-C values remained within the normal range during 14-day, once daily treatment with 15 mg.

UDCA is the only drug which is approved in China for PBC and approximately 40% PBC patients have an inadequate response to or are unable to tolerate UDCA. Obeticholic Acid (OCA), which is not approved in China, is the only approved medicine in the U.S. for PBC patients who have an inadequate response to or are unable to tolerate UDCA. However, there are significantly increased pruritus rates and LDL-C levels in patients with OCA treatment. Lack of pruritus and LDL-C level increase at the therapeutic dose makes ASC42 a potential best-in-class PBC drug. Gannex intends to start a Phase III trial in the U.S. and European Union after the completion of the Phase II study in China.

Jidong Jia, MD, Director of the Liver Disease Center, Beijing Friendship Hospital, Capital Medical University, Deputy Director of National Clinical Research Center for Digestive Diseases, stated, "There is a significant unmet medical need for PBC treatment, and from the Phase I data, there was no pruritus observed during 2-week treatment with the human therapeutic dose of ASC42. I am pleased to be the principal investigator of clinical trials of ASC42 for PBC indication."

Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis said, "After the recent progress in CHB functional cure with our immunotherapy, we have now obtained the approval of PBC as the third hepatobiliary disease indication of ASC42 by China NMPA. We are working very hard to transform ourselves into a global R&D leader in hepatobiliary diseases."

About Ascletis

Ascletis is an innovative R&D driven biotech listed on the Hong Kong, S.A.R., China Stock Exchange (1672.HK), a global platform covering the entire value chain from discovery and development to manufacturing and commercialization. Ascletis is committed to developing and commercializing innovative drugs in the areas of viral diseases, NASH/PBC, and cancer (oral cancer metabolic checkpoint and immune checkpoint inhibitors) to address unmet medical needs both in China and globally. Led by a management team with deep expertise and a proven track record, Ascletis targets those therapeutic areas with unmet medical needs from a global perspective, and efficiently advances the developments of pipelines with an aim of leading in global competition. To date, Ascletis has three marketed products and 18 robust R&D pipelines of drug candidates with global competitiveness, and is actively exploring new therapeutic areas.

1. Viral Diseases: (1) Hepatitis B Virus (functional cure): focus on breakthrough therapies for CHB functional cure with a subcutaneously-injected PD-L1 antibody – ASC22 and Pegasys® as cornerstone drugs. (2) HIV/AIDS: ASC22, an immune therapy to restore HIV-specific immune responses and eventually lead to a functional cure of HIV-infected patients. (3) Hepatitis C: successfully launched an all-oral regimen of combining ASCLEVIR® and GANOVO® (RDV/DNV regimen). 

2. Non-alcoholic Steatohepatitis/Primary Biliary Cholangitis: 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, THRβ and FXR, three fixed-dose combinations for NASH and one PBC program targeting FXR.

3. Cancer (oral cancer metabolic checkpoint and immune 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 immune checkpoint inhibitors.

4. Exploratory Indications: Acne: Following NASH and recurrent GBM, the third indication for ASC40 has been approved to enter Phase 2 clinical trial.

Source: Ascletis Pharma Inc.