--Enrollment of the total 12 subjects is expected to be completed in August 2022

--The DDI study on ASC42 in the U.S. is expected to be completed by the beginning of the fourth quarter 2022

--This DDI study and ongoing Phase II clinical trial in PBC patients in China will provide more evidence to support upcoming Phase III clinical trials in China, the U.S. and the European Union

Shanghai, China, August 16, 2022-- Gannex Pharma Co., Ltd. (“Gannex”), a wholly owned company of Ascletis Pharma Inc. (HKEX: 1672) today announces that it has completed the first subject dosing in the U.S. drug-drug interaction (DDI) study of Farnesoid X receptor (FXR) agonist ASC42 for treatment of primary biliary cholangitis (PBC). This DDI study is expected to enroll 12 subjects in total in August 2022 and be completed by the beginning of the fourth quarter 2022 in the U.S. The DDI study and ongoing Phase II clinical trial in PBC patients in China will provide more evidence to support upcoming Phase III clinical trials in China, the U.S. and the European Union for treatment of PBC.

PBC is a chronic autoimmune cholestatic disease and frequently progresses to liver fibrosis and cirrhosis requiring liver transplantation or resulting in death. In response to the increasing incidence, Asian Pacific Association for the Study of the Liver (APASL) developed the clinical practice guidance on the diagnosis and management of patients with PBC in 2022. PBC is gaining extensive attention as both the incidence and prevalence has showed an increasing tendency globally ^[1].

An epidemiology study indicates that there were approximately 120,000 PBC patients in the U.S. in 2014^[2]. Ursodeoxycholic acid (UDCA) is the standard treatment for PBC, however, approximately 40% PBC patients have an inadequate response to or are unable to tolerate UDCA^[3]. For those patients with insufficient UDCA response or intolerance, Obeticholic Acid (OCA) is the only approved medicine in the U.S. while it has not been approved in China yet. Additionally, OCA may significantly cause pruritus and low density lipoprotein cholesterol (LDL-C) levels to rise.

ASC42 is an in-house developed, novel non-steroidal, selective, potent FXR agonist with best-in-class potential and global intellectual property. Previous Phase I clinical trial in the U.S. (ClinicalTrials.gov Identifier: NCT04679129) demonstrated that ASC42 might be a potentially best-in-class PBC drug candidate as LDL-C levels were in normal range with no pruritus occurrence, and FXR target engagement biomarker FGF19 increased 1,780% when ASC42 was dosed at 15 mg, once daily (QD) during the 14-day treatment.

Currently, FXR agonist ASC42 is in Phase II clinical trial in China. The Phase II study (ClinicalTrials.gov Identifier: NCT05190523) consists of three ASC42 active treatment arms (5 mg, 10 mg and 15 mg) and one placebo control arm at the ratio of 1:1:1:1 and is expected to enroll a total of 100 patients who have an inadequate response to or are unable to tolerate UDCA. The treatment duration is 12 weeks.

Gannex intends to initiate Phase III clinical trials in China, the U.S. and the European Union after the completion of the ongoing Phase II clinical trial in China.

“It only took us two months to complete the first subject dosing after the application of DDI study was approved by the U.S. FDA. This fast progress, once again, demonstrated the execution excellence of our team. Gannex is advancing clinical trials of FXR agonist ASC42 in both China and the U.S. to meet the unmet medical needs for patients with PBC. We are dedicated to improving the current treatments of PBC and providing more options for patients.” said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.

[1] Lv T, Chen S, Li M, et al. Regional variation and temporal trend of primary biliary cholangitis epidemiology: A systematic review and meta-analysis. J Gastroenterol Hepatol. 2020;36:1423–1434.

[2] Lu M, Zhou Y, Haller I V, et al. Increasing Prevalence of Primary Biliary Cholangitis and Reduced Mortality With Treatment [J]. Clin Gastroenterol Hepatol 2018, 16(8): 1342-50 e1. DOI: 10.1016/j.cgh.2017.12.033.

[3] Lindor K D, Bowlus C L, Boyer J, et al. Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases [J]. Hepatology 2019, 69(1): 394-419. DOI: 10.1002/hep.30145.