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 three clinical stage drug candidates against three different targets – FASN, THR-beta and FXR, and three combination therapies. 


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


ASC42, an Oral FXR Agonist for NASH



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• A novel non-steroidal, selective, potent FXR agonist 

• U.S. IND approved in October 2020 

• In two NASH animal models, ASC42 demonstrated the significant improvement in liver steatosis, inflammation, and fibrosis 

• An oral tablet formulation developed with proprietary therapy, stable at room temperature 

• Combination opportunities with ASC41 (THR-β) and ASC40 (FASN)






Publications


Title

Venue

Type

Date

Novel, first-in-class, fatty acid synthase inhibitor, TVB-2640 versus    placebo demonstrates clinically significant reduction in liver fat by MRI-PDFF in NASH

AASLD

oral

11/2020

Novel, first-in-class, fatty acid synthase inhibitor, TVB-2640 versus    placebo demonstrates clinically significant reduction in liver fat by MRI-PDFF in NASH

EASL International Liver Congress

oral

08/2020

The FASN inhibitor TVB-2640 is efficacious in a new 3D human liver microtissue model of NASH

EASL International Liver Congress

poster

08/2020

Fatty Acid Synthase Inhibitor TVB-2640 Reduces Hepatic de Novo      Lipogenesis in Males With Metabolic Abnormalities

Hepatology 2020

paper

07/2020

Progressive Reductions in Hepatic DNL with Increasing Doses of TVB-2640, a First-in-Class Pharmacologic Inhibitor of FASN

Keystone Symposium on Organ Crosstalk in Obesity and NAFLD

poster

01/2018

First in human study of the first-in-class fatty acid synthase (FASN) inhibitor TVB-2640

AACR Annual Meeting

oral

04/2017

Establishing the foundation for a novel, first-in-class, fatty acid 

synthase inhibitor, TVB-2640, for the treatment of NASH

EASL International Liver Congress

poster

04/2017