Our Focus

Gannex, a wholly-owned company of Ascletis,is fully dedicated to the R&D and commercialization of new drugs in the field of NASH. Gannex has two clinical stage drug candidates against two different targets – FASN, THR-beta . 


ASC40, a Global First-in-class, Oral FASN Inhibitor for NASH


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FASN: fatty acid synthase  NASH: non-alcoholic steatohepatitis   NAFLD: non-alcoholic fatty liver disease

C. Estes et al., J HEP 2018 (69): 896–904



Efficacy and Safety of ASC40 Treatment in Patients with NASH


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Rohit Loomba et al. 2020, Hepatology 72; 103.EASL 2020 Oral Presentation


ASC41, an Oral THR-β Agonist for NASH

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• Liver-targeted prodrug (ASC41) and active moiety (ASC41-A) is selective for THR-β 

• In two NASH animal models, at 1/10 dose of MGL-3196, ASC41 demonstrated the same improvement in liver steatosis, inflammation and fibrosis 

• A highly potent and selective THR-β agonist with anticipated human efficacious dose <10 mg QD

 Proprietary oral tablet formulation stable at room temperature and whose exposure is same as solution formulation in dogs 

• 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 

• Combination opportunities with ASC42 (FXR) and ASC40 (FASN)


Phase I Clinical Trial Results of ASC41


• 65 subjects with elevated low-density lipoprotein cholesterol (LDL-C) (> 110 mg/dL), a population characteristic of non-alcoholic fatty liver disease (NAFLD) 

• In the single-ascending dose portion of the study, preliminary data suggest that ASC41 is safe and well tolerated up to a dose of 20 mg. Furthermore, ASC41 tablet formulation showed a dose-proportional pharmacokinetic profile from 1 mg to 20 mg 

• In the multiple-ascending dose (MAD) portion of the study, preliminary data suggest that after 14 days of once daily oral dosing, subjects demonstrate clinically meaningful and statistically significant reduction in LDL-C and triglycerides compared to placebo, as shown in the table below:


Phase I Clinical Trial Results of ASC41.png


• ASC41 had a benign adverse event profile at all doses following 14-day treatment, with no grade 3 or above adverse events, no serious adverse events or premature discontinuations

• ASC41 tablet formulation displayed a dose-proportional pharmacokinetic profile from 1 mg to 5 mg following once daily, 14-day dosing






Publications


Title

Venue

Type

Date

ASC41, a thyroid hormone receptor β agonist, showed little drug interaction, significant lipid reduction and comparable pharmacokinetic profiles among Chinese and US healthy subjects and patients with non-alcoholic fatty liver disease (NAFLD): results from two phase 1 studies

The Liver Meeting® 2023 of the American Association for the Study of Liver Diseases (AASLD)
Poster11/2023
A Phase Ib Study to Evaluate the Safety, Tolerability   and Pharmacokinetics of ASC 41 a THR-β Agonist, for 28-days in Overweight and   Obese Subjects with Elevated LDL-C, a Population with Characteristic s Of   NAFLDThe Liver Meeting® 2021 of the American  Association for the Study of Liver Diseases (AASLD)Poster11/2021
Significant lipid lowering by ASC41, an oral tablet,   liver-targeted THRβ agonist, in a phase I randomized, double-blind, placebo   controlled single- and multiple-ascending dose studyThe   International Liver Congress™ 2021 of the European Association for the Study   of the Liver (EASL)Poster04/2021
Significant Improvement of   NAFLD Activity Scores and Liver Fibrosis by ASC41, a Selective THR-β Agonist,   in High Fat Diet Induced NASH SD RatsThe   International Liver Congress™ 2021 of the European Association for the Study   of the Liver (EASL)Poster04/2021
Novel, first-in-class, fatty acid synthase inhibitor,   TVB-2640 versus placebo demonstrates clinically significant reduction in   liver fat by MRI-PDFF in NASHThe Liver Meeting® 2020 of the American   Association for the Study of Liver Diseases (AASLD)Oral11/2020
Novel, first-in-class, fatty   acid synthase inhibitor, TVB-2640 versus placebo demonstrates clinically   significant reduction in liver fat by MRI-PDFF in NASHThe   Liver Meeting® 2020 of the American Association for the Study of Liver   Diseases (AASLD)Oral08/2020
The FASN inhibitor TVB-2640 is efficacious in a new 3D   human liver microtissue model of NASHThe   Liver Meeting® 2020 of the American Association for the Study of Liver   Diseases (AASLD)Poster08/2020
Fatty Acid Synthase Inhibitor   TVB-2640 Reduces Hepatic de Novo Lipogenesis in Males With Metabolic   AbnormalitiesHepatology 2020Paper07/2020
Progressive Reductions in   Hepatic DNL with Increasing Doses of TVB-2640, a First-in-Class Pharmacologic   Inhibitor of FASNKeystone Symposium on Organ Crosstalk in   Obesity and NAFLDPoster01/2018
Establishing the foundation for   a novel, first-in-class, fatty acid synthase inhibitor, TVB-2640, for   the treatment of NASHThe   International Liver Congress™ 2017 of the European Association for the Study   of the Liver (EASL)Poster04/2017