Gannex Announces Positive Phase I Clinical Results on Its THR-β Agonist ASC41

Doses Selected for Phase 2 Trial in Patients with NASH


Shanghai, China, 12 January 2021-- Gannex, a wholly owned company of Ascletis Pharma Inc. (HKEX: 1672) and fully dedicated to the R&D and commercialization of new drugs in the field of non-alcoholic steatohepatitis (NASH), today announces the positive phase I clinical results of ASC41 oral tablet, a liver-targeted prodrug. The active metabolite of ASC41 is a selective thyroid hormone receptor beta (THR-β) agonist.


This phase I trial is a randomized, double-blind, placebo controlled single- and multiple-ascending dose study in 65 subjects with elevated low-density lipoprotein cholesterol (LDL-C) (> 110 mg/dL), a population characteristic of non-alcoholic fatty liver disease (NAFLD). ASC41 has been formulated in commercially ready oral tablets developed in-house using proprietary technology. 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.

 

Placebo-adjusted     relative change (mean) from baseline after 14 days of once daily oral   dosing of   ASC41 tablets


1 mg  

(n=12)

2 mg 

(n=12)

5 mg 

(n=12)

Placebo-adjusted LDL-C reduction

P-value vs placebo

-0.42%

p=0.947

-11.94%

p=0.052

-19.99%

p=0.002

Placebo-adjusted triglyceride

reduction

P-value vs placebo

-39.43%

p=0.002

-31.06%

p=0.029

-34.49%

p=0.015


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

 

“We are pleased with the excellent pharmacokinetic profile using our in-house developed tablet formulation”, said Handan He, PhD, Chief Scientific Officer of Ascletis, “The successful development of the commercially-ready oral formulation at this early stage will accelerate our clinical development.”

 

“We are excited about the LDL-C and triglyceride reductions in this patient population characteristic of NAFLD, at low doses of ASC41,” said Melissa Palmer, MD, Chief Medical Officer of Gannex, “These results support advancement of the ASC41 clinical program for the indication of NASH.”


About Ascletis

Ascletis is an innovative R&D driven biotech and listed on Hong Kong Stock Exchange (1672.HK). Ascletis is committed to developing and commercializing innovative drugs in the areas of viral hepatitis, NASH and HIV/AIDS for unmet medical needs in China and globally. Led by a management team with deep expertise and a proven track record, Ascletis has developed into a fully integrated platform covering the entire value chain from discovery and development to manufacturing and commercialization.

Ascletis has three marketed products and thirteen R&D pipeline drug candidates or combination therapies (nine of them developed in-house). 1. Viral hepatitis: (i) Hepatitis B: focus on breakthrough therapies for HBV clinical cure with subcutaneously injected PD-L1 antibody - ASC22 and Pegasys® as cornerstone drugs. (ii) Hepatitis C: successfully launched all oral regimen of ASCLEVIR® and GANOVO® combination (RDV/DNV regimen); and ASC18 fixed dose combination (FDC) is an upgraded version of RDV/DNV regimen with bridging study finished. 2. NASH: 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 pre-clinical stage combination therapies. 3. HIV/AIDS: ASC09F is a FDC treatment of HIV targeting protease. The clinical trial application of ASC09F has been approved. For more information, please visit www.ascletis.com.

 

Contact:

Ascletis Pharma Inc.

Chenlin Li, +86-159-6815-8530

pr@ascletis.com

ir@ascletis.com