Shanghai, China and Tel-Aviv, Israel 9 Sept 2020 -- Gannex Pharma Co., Ltd., a wholly owned company of Ascletis Pharma Inc. (HKEX:1672) and Galmed Pharmaceuticals Ltd. (NASDAQ: GLMD) announces today that they have entered into a research agreement aiming at combination therapy of ASC41 (THR-beta agonist) and Aramchol (SCD 1 inhibitor) for the treatment of non-alcoholic steatohepatitis (NASH). The financial details of this transaction are not disclosed.

ASC41 is an oral thyroid hormone receptor beta (THR-beta) agonist which recently received IND approval from China’s National Medical Products Administration (NMPA) to conduct clinical trials for NASH indication. Topline data of Phase Ⅰ safety, PK and preliminary efficacy (LDL-C) in healthy volunteers with LDL-C > 110 mg/dL is expected to be available by the end of 2020. ASC41’s active moiety selectively activates THR-beta resulting in the improvement of steatosis/lipotoxicity, inflammation, ballooning, fibrosis in both direct and indirect manner. In two NASH animal models, ASC41 demonstrated the same improvement in liver steatosis, inflammation and fibrosis at 1/10 dose of Resmetirom (MGL-3196), another THR-beta agonist currently in Phase Ⅲ clinical trial.

Aramchol is a novel synthetic small molecule, a conjugate of cholic acid and arachidic acid, linked by a stable amide group. Aramchol exerts its anti-steatotic and anti-fibrotic effects via inhibition of SCD 1 expression in hepatocytes and hepatic stellate cells (HSCs). In hepatocytes, reduction of SCD 1 results in elevation of AMPK, FA oxidation and Glutathione ratio. In HSC’s inhibition of SCD 1 results in specific up regulation of PPAR γwhich blocks collagen production. In Phase Ⅱ clinical trials for NASH, Aramchol significantly reduced liver fat, improved liver histology i.e., ballooning and fibrosis, hepatic biochemistry and glycemic parameters with a favorable safety and tolerability profile. Aramchol is currently in a Phase Ⅲ registrational study for NASH and fibrosis (ARMOR) and has been granted Fast Track designation status by the FDA for the treatment of NASH.

“There is a significant medical need and a large potential pharmaceutical market for NASH treatment. There are currently no drugs licensed for the treatment of NASH in US, Europe and China. ASC41 is a THR-beta agonist that improves steatosis, inflammation and fibrosis, and  Aramchol, a SCD 1 inhibitor,  reduces glycemic index and fibrosis. Therefore, combination therapy of the two drug candidates could result in synergistic effect for the treatment of NASH,” said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.

"It is clear today that NASH is a chronic condition with multiple liver pathologies. Among all pathologies, excessive liver fat, high glycemic index and fibrosis are major treatment challenges. By combining ASC41, THR-beta agonist, which is clinically proven to rapidly reduce liver fat and improved blood lipids profile, with Aramchol, SCD 1 inhibitor, which is clinically proven to reduce glycemic index and fibrosis, physicians will have good and solid toolbox and will be able to normalize NASH patients for life and control the disease," said Allen Baharaff, President and CEO of Galmed. "We believe that combining these two distinct and selective compounds with complementary mechanisms will provide a perfect treatment for NASH.”