Gannex Announces Completion of the U.S. Phase I Trial of ASC43F, an In-House Developed First-in-Class Dual Targeting Fixed-dose Combination Tablet for NASH

• ASC43F was safe and well tolerated in healthy subjects with no clinically significant study drug related adverse events
• Pharmacokinetic parameters of ASC41 and ASC42 from ASC43F are similar to those of ASC41 and ASC42 monotherapy
• Phase I trial completed two months after the U.S. IND approval, demonstrating execution excellence

SHANGHAI, Jan. 4, 2022 /PRNewswire/ -- Gannex Pharma Co., Ltd., a wholly owned company of Ascletis Pharma Inc. (HKEX: 1672), today announces the completion of the U.S. Phase I trial of ASC43F, an in-house developed, first-in-class dual targeting fixed-dose combination (FDC) tablet for non-alcoholic steatohepatitis (NASH).

ASC43F is a once-a-day (QD), single tablet, FDC of 5 mg ASC41, a thyroid hormone receptor beta (THRβ) agonist, and 15 mg ASC42, a farnesoid X receptor (FXR) agonist. The U.S. Phase I trial (ClinicalTrials.gov Identifier: NCT05118516) was an open-label, single-dose study evaluating the safety, tolerability and pharmacokinetics of ASC43F in healthy subjects. The results showed that ASC43F was safe and well tolerated, without clinically significant adverse effects. The pharmacokinetic parameters of ASC41 and ASC42 from ASC43F are similar to those of ASC41 and ASC42 as monotherapy.

Previous Phase I studies in the U.S. and China have shown ASC41 at 5 mg to be safe and well tolerated in both healthy volunteers, overweight and obese subjects and patients with non-alcoholic fatty liver disease (NAFLD). In these studies, ASC41 significantly reduced 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.

Previous Phase I clinical data indicated that ASC42 was safe and well tolerated, with no pruritus and with LDC-C values remaining within normal range during 14-day treatment with once-daily 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 dose.

Dr. Handan He, Chief Scientific Officer of Ascletis, stated, "The U.S. Phase I study confirmed a favorable safety profile of ASC43F and similar PK parameters of ASC41 and ASC42 from ASC43F as compared to those of ASC41 and ASC42 single tablets. ASC41 and ASC42 have complementary MOA's, as THRβ agonists have shown primarily anti-metabolic effects, while FXR agonists have shown primarily anti-fibrotic, as well as anti-inflammatory effects. Thus, a combination of these two molecules can potentially work synergistically, targeting all NASH components - steatosis, ballooning, inflammation and fibrosis. In addition, a THRβ agonist combined with an FXR agonist may reduce potential adverse events, such as lowering atherogenic risks, by decreasing the elevated LDL-C that has been associated with other FXR agonists."

Melissa Palmer, MD, Chief Medical Officer of Gannex, stated, "We are excited to see the positive results from the Phase I study of ASC43F, which will support continued development of this promising dual targeting FDC into NASH patients. I'm proud of the execution excellence of our clinical team, as we had the first subject dosed in only half a month after IND approval and completed the trial two months after the IND approval."

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 20 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) COVID-19 pipeline: currently includes (i) ritonavir oral tablet (100 mg), an authorized product, (ii) ASC10, an oral RNA dependent RNA polymerase (RdRp) inhibitor and (iii) ASC11, an oral 3-chymotrypsin like protease (3CLpro) inhibitor. (3) HIV/AIDS: ASC22, an immune therapy to restore HIV-specific immune responses and eventually lead to a functional cure of HIV-infected patients. (4) 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. For more information, please visit www.ascletis.com.