Ascletis Announced Four Clinical and Preclinical Study Abstracts of NASH and HBV Accepted as Poster Presentations by the International Liver Congress™ 2021

HANGZHOU,Chinaand SHAOXING,China,April 12,2021 -- Ascletis Pharma Inc. (HKEX:1672) announces today that four clinical and preclinical study abstracts of NASH and HBV have been accepted by the International Liver Congress™ 2021 as poster presentations. The summary of the four abstracts are shown as below:

1. Title: Significant lipid lowering by ASC41 oral tablet，a liver targeted THR-β agonist，in a Phase I randomized，double-blind，placebo controlled single- and multiple-ascending dose study

Abstract/poster number:1851

Category:NAFLD therapy

Results: In the single-ascending dose portion of the study,preliminary data suggestthat 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.

Conclusion: These data supported advancement of the ASC41 clinical program for the indication of NASH.

2.Title:Significant improvement of NAFLD activity scores and liver fibrosis by ASC41,a selective THR-β agonist,in high fat diet induced NASH SD rats

Abstract/poster number: 1908

Category:NAFLD therapy

Results: ASC41 demonstrated dose-dependently reductions in liver steatosis,inflammatory cell infiltration,ballooning change and total non-alcoholic fatty liver disease activity score (NAS). ASC41 at 1.5 mg/kg and 4.5 mg/kg showed higher NAS reductions relative to MGL3196 at 5 mg/kg (P=0.01 and P<0.001). ASC41 at 0.5 mg/kg showed a 23.9% reduction in NAS score and a 14.4% reduction in liver fibrosis,similar to MGL3196 at 5 mg/kg. ASC41 at 1.5 mg/kg and 4.5 mg/kg both showed a significant decrease in serum LDL-C.

Conclusion:ASC41 demonstrated NAS reductions and anti-fibrotic benefits in the high fat diet induced NASH SD rats. The current efficacy data supported the advancement of ASC41 into clinical trials in human.

3. Title: Significant improvement of NAFLD activity scores and liver fibrosis by ASC42，a novel non-steroidal FXR agonist，in high fat diet induced NASH mice

Abstract/poster number: 1961

Category:NAFLD therapy

Results: ASC42 demonstrated dose-dependently reductions in liver steatosis,ballooning change and total non-alcoholic fatty liver disease activity score (NAS). ASC42 at 30 mg/kg showed a significantly higher NAS reduction relative to OCA at 30 mg/kg (P<0.001). ASC42 at 3 mg/kg showed a 46.2% reduction in NAS score and a 15.2% reduction in liver fibrosis,similar to OCA at 30 mg/kg. Total glyceride in liver exhibited a dose-proportional decrease in ASC42-treated mice.

Conclusion:ASC42 demonstrated NAS reductions and anti-fibrotic benefits in the mice NASH Model.These data supported the advancement of ASC42 into clinical trials in human.

4. Title: Significant in-vitro and in-vivo inhibition of HBsAg and HBV pgRNA with ASC42，a novel non-steroidal FXR agonist

Abstract/poster number: 1917

Category:Viral hepatitis A,B,C,D,E: virology

Results: In PHH model,the control compound ETV showed the expected inhibitory activity on HBV DNA,but had no inhibition on HBV pgRNA and HBsAg,while ASC42 inhibited HBsAg,HBV pgRNA,and HBV DNA dose-dependently,with EC50 of 0.79μM,0.09μM and 0.62μM,respectively(Figure 1A-D). In AAV/HBV mice model,after ETV (0.1 mg/kg) monotherapy,HBV DNA in mice plasma decreased significantly,while HBV pgRNA and HBsAg showed no obvious reduction. ASC42 demonstrated a dose-dependent inhibition of HBV pgRNA,HBsAg,HBV DNA in mice plasma. High-dose group of ASC42 (60 mg/kg) inhibited HBV pgRNA,and HBV DNA by 0.60 log10 copy/μl (P<0.01),0.38 log10 IU/μl (P =0.002),and 0.77 log10 copy/μl (P <0.05),respectively,relative to vehicle control group (Figure 1 E-F).

Conclusion:These in-vitro and in-vivo studies demonstrated that ASC42,a FXR agonist,significantly inhibited HBV DNA,HBV pgRNA and HBsAg,indicating that ASC42 has therapeutic potential to functional cure of HBV infection. The results support the advancement of ASC42 into clinical trials in human.

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 NASH,cancer lipid metabolism and oral checkpoint inhibitors,viral hepatitis 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 seventeen R&D pipeline drug candidates or combination therapies (eleven of them developed in-house). 1. 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. 2. Cancer lipid metabolism and oral checkpoint inhibitors: focus on a pipeline of oral inhibitors targeting FASN which plays a key role in cancer lipid metabolism and a pipeline of oral PD-L1 small molecule inhibitors as the next generation checkpoint inhibitors. 3. 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. 4. 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.