-- Demonstrating execution excellence of Gannex clinical team

--ASC43F is a first-in-class dual targeting fixed-dose combination for NASH

--Animal studies showed that dual targeting THRβ and FXR has synergies on reducing liver fat, inflammation and fibrosis

SHANGHAI, Nov. 18, 2021 -- 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."