ASC-42

HANGZHOU, China and SHAOXING, China, April 3, 2024 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX:1672, "Ascletis") announces today the strategic decisions on farnesoid X receptor (FXR) agonist ASC42. After thorough analysis of the Phase II trial data of ASC42 for primary biliary cholangitis (PBC) (ClinicalTrials.gov: NCT05190523), the Company made a strategic decision not to pursue further clinical trials of ASC42 for PBC indication. This decision is based on the efficacy and safety data from the 12-week Phase II study, which consisted of three ASC42 active treatment arms (5 mg, 10 mg and 15 mg QD) and one placebo control arm. The results indicated that ASC42 did not show competitiveness to new PBC drug candidates currently in development and registrational stages. Furthermore, the Company also decided not to pursue further clinical studies of ASC42 as an FXR agonist in combination for non-alcoholic steatohepatitis (NASH) (ASC43F) and clinical studies of ASC42 for hepatitis B virus (HBV) indication. As of December 31, 2023, the Group had cash and cash equivalent and time deposits of approximately RMB 2.3 billion. These strategic decisions are part of the Company's efforts to continue to evaluate and optimize its research & development pipeline to increase efficiency and preserve cash. The savings from discontinuing these planned clinical trials will be used to accelerate clinical development of ASC41 and ASC40 for NASH indication and in-house discovery for global first-in-class or best-in-class drug candidates. The positive interim results from ASC41 Phase II trial in biopsy-confirmed NASH patients demonstrated ASC41 as a potential best-in-class thyroid hormone receptor β (THRβ) agonist. As a first-in-class FASN inhibitor, the Phase IIb study showed ASC40 (denifanstat) achieved statistically significant results for both NASH resolution and fibrosis improvement in biopsy-confirmed NASH patients with stage 2 or 3 fibrosis after 52-week treatment. About Ascletis Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), covering the entire value chain from discovery and development to manufacturing and commercialization. Led by a management team with deep expertise and a proven track record, Ascletis focuses on three therapeutic areas with unmet medical needs from a global perspective: viral diseases, non-alcoholic steatohepatitis (NASH) and oncology. Through excellent execution, Ascletis rapidly advances its drug pipeline with an aim of leading in global competition. To date, Ascletis has multiple drug candidates in its R&D pipeline. The most advanced drug candidates include ASC22 (CHB functional cure), ASC40 (acne), ASC40 (recurrent glioblastoma), ASC40 (NASH), ASC41 (NASH) and ASC61 (advanced solid tumors). For more information, please visit . SOURCE Ascletis Pharma Inc.

Ascletis Pharma is pulling the plug on its farnesoid X receptor (FXR) agonist ASC42, which was being developed across multiple indications. The move follows an analysis of Phase II efficacy and safety data in primary biliary cholangitis (PBC), revealing that ASC42 "did not show competitiveness" compared to other drug candidates currently in late-stage testing for the same indication.In addition to halting the PBC programme, Ascletis is also terminating further clinical studies of ASC42 as part of a combination regimen for metabolic dysfunction-associated steatohepatitis (MASH), formerly referred to as non-alcoholic steatohepatitis (NASH), and as a monotherapy for hepatitis B virus infection.Speed work on other MASH assetsAscletis says the savings generated from discontinuing the planned clinical trials will be redirected towards accelerating development of two other potential MASH candidates, ASC41 and ASC40, as well as supporting the Chinese biotech's in-house discovery efforts.ASC41 is a once-daily oral THRβ agonist that led to significant reductions in fat content in patients with biopsy-confirmed MASH, according to interim Phase II results unveiled earlier this year. The compound is in the same class as Madrigal Pharmaceuticals' Rezdiffra (resmetirom), which became the first approved MASH treatment when US regulators signed off on it last month.Ascletis' drug has also been at the centre of a dispute with Viking Therapeutics, which claimed that ASC41 is based on stolen trade secrets revolving around its own THRβ drug, VK2809.Meanwhile, Asceltis said its FASN inhibitor ASC40, also known as denifanstat, achieved statistically significant results for both MASH resolution and fibrosis improvement in a Phase IIb study of NASH patients with stage 2 or 3 fibrosis after 52 weeks of treatment. ASC40 is also in late-stage development as an acne treatment, and in combination with bevacizumab for patients with recurrent glioblastoma.The company's most advanced drug candidate is ASC22, a subcutaneously injected PD-L1 antibody currently in Phase II as a potential functional cure for both chronic hepatitis B and HIV.