First Subject Dosed in the U.S. Phase I Trial for ASC43F Only Half a Month after IND Approval by the U.S. FDA

SHANGHAI, Nov. 17, 2021 /PRNewswire/ -- Gannex Pharma Co., Ltd., a wholly owned company of Ascletis Pharma Inc. (HKEX: 1672), today announces dosing of the first subject in the U.S. Phase I trial for ASC43F, a first-in-class, fixed-dose combination (FDC) oral tablet with dual targets of thyroid hormone receptor beta (THRβ) and farnesoid X receptor (FXR) for the treatment of non-alcoholic steatohepatitis (NASH). The U.S. Phase I trial is an open-label, single-dose study to evaluate the safety, tolerability and pharmacokinetics of ASC43F in healthy subjects.

ASC43F is a single tablet, once-a-day (QD), FDC of 5 mg ASC41 (THRβ agonist) and 15 mg ASC42 (FXR agonist). Previous Phase I studies in the U.S. and China have shown ASC41 to be well tolerated, has favorable PK profiles in both healthy volunteers and patients with NAFLD, and significantly reduces low density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) in overweight and obese subjects with elevated LDL-C, a population that is characteristics of NASH.

The Phase I clinical data indicated that ASC42 is safe and well tolerated, with no pruritus observed and LDC-C values remained within normal range during 14-day treatment of the once-daily human therapeutic dose of 15 mg. FXR target engagement biomarkers Fibroblast Growth Factor 19 (FGF19) increased 1,780% and 7α-hydroxy-4-cholesten-3-one (C4) decreased 91% on Day 14 of treatment with 15 mg, once-daily.

Animal studies showed that PK parameters of ASC42 and ASC41A, the active metabolite of ASC41, in or from ASC43F tablets remained approximately unchanged as compared to the PK parameters of single ASC41 and ASC42 tablets.

Dr. Handan He, Chief Scientific Officer of Ascletis, said, "We had previously confirmed good safety and PK profiles in humans for both ASC41 and ASC42 tablets. Animal studies showed good efficacy in the rat NASH model after the co-administration of ASC41 and ASC42, and demonstrated comparable PK parameters between ASC43F and single tablets of ASC41 and ASC42. We are confident that ASC43F has the potential to be an effective drug candidate for NASH treatment."

Melissa Palmer, MD, Chief Medical Officer of Gannex, said, "I'm proud of the excellent execution of our clinical development team as we just received the IND approval by U.S. FDA nearly half a month ago. In addition, the overall sentiment from the American Association for the Study of Liver Diseases (AASLD) meeting that completed this week underscored the importance of studying combination therapy for this difficult to conquer liver disease."

About Ascletis

Ascletis is an innovative R&D driven biotech listed on the Hong Kong 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.