Ascletis Announced Four Clinical and Preclinical Study Abstracts of NASH and HBV

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Abstract/poster number: 1851

Category: NAFLD therapy

Results: 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.

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 ASC42a novel non-steroidal FXR agonistin high fat diet induced NASH mice

Abstract/poster number: 1961

Category: NAFLD therapy

Results: ASC42 demonstrated dose-dependently reductions in liver steatosis, inflammatory cell infiltration, 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 ASC42a novel non-steroidal FXR agonist

Abstract/poster number: 1917

Category: Viral hepatitis A, B, C,…



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