Gannex Announces U.S. IND Approval of ASC43F, a First-in-Class Dual-Target Fixed-Dose Combination for NASH

Gannex Pharma Co., Ltd., a wholly owned company of Ascletis Pharma Inc. (HKEX: 1672), today announces the Investigational New Drug (IND) application approval by U.S. Food and Drug Administration (FDA) and initiation of global development of ASC43F, a first-in-class, fixed-dose combination (FDC) with dual targets of thyroid hormone receptor beta (THRβ) and farnesoid X receptor (FXR) for the treatment of non-alcoholic steatohepatitis (NASH).

ASC43F is a single tablet, once-a-day (qd), FDC of ASC41 and ASC42. ASC41 is an oral hepatic targeting THRβ agonist prodrug under global clinical development. Previous Phase I studies in the U.S. and China have shown ASC41 to be well tolerated and to significantly reduce 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. ASC42 is a novel non-steroidal, selective, potent, oral FXR agonist under global clinical development. The Phase I clinical data indicated that no pruritus was observed 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% on Day 14 of treatment with 15 mg, once-daily and 7α-hydroxy-4-cholesten-3-one (C4) decreased 91% on Day 14 of treatment with 15 mg, once-daily.

The U.S. IND approval was based on the efficacy data in the rat NASH model after the coadministration of ASC41 and ASC42, where the combination therapy showed significant improvements on serum TG and liver TC, inflammation, ballooning, NAFLD Activity Score (NAS) and fibrosis. In addition, the data to be presented at the upcoming American Association for Study of Liver Diseases annual conference shown that the dog PK parameters of ASC42 and ASC41A, the active metabolite of ASC41, in/from ASC43F tablets remained approximately unchanged as compared to those of single ASC41 and ASC42 tablets.

Dr. Handan He, Chief Scientific Officer of Ascletis, stated, "NASH is a metabolic syndrome with a complex underlying pathophysiology. Thus, combination treatments with different mechanisms of action and/or different targets is a promising approach to combat this liver disease. THRβ agonists are believed to reduce liver fat through improving mitochondrial function, while FXR engagement has strong anti-fibrotic effects in addition to anti-inflammatory effects. Thus, ASC43F may have strong effects on reducing liver fat, necroinflammation and fibrosis with dual targeting THRβ and FXR."

Melissa Palmer, MD, Chief Medical Officer of Gannex, stated, "We have a very strong NASH pipeline with six assets under development, including three FDC agents, which are all first-in-class. FDCs may have advantages over monotherapy by potentially reducing adverse events, improving efficacy, and reducing the need for multiple different pills."

About Ascletis

Ascletis is an innovative R&D driven biotech listed on the Hong Kong, S.A.R., China 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, THRβ 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: (1) Hepatitis B: focus on breakthrough therapies for CHB functional cure with a subcutaneously-injected PD-L1 antibody – ASC22 and Pegasys® as cornerstone drugs. (2) Hepatitis C: successfully launched an all-oral regimen of combining ASCLEVIR® and GANOVO® (RDV/DNV regimen). (3) 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.

Source: Ascletis Pharma Inc.