SHANGHAI, China I January 19, 2023 I Hepagene Therapeutics, Inc. a clinical stage biopharmaceutical company focusing on developing novel therapies for patients with chronic liver diseases, today reported positive top-line results from the Phase 2a RISE clinical trial of HPG1860, a next generation non-bile acid, liver selective farnesoid X receptor (FXR) agonist, for the treatment of non-alcoholic steatohepatitis (NASH). The trial met its primary endpoint of safety and tolerability, and HPG1860 also achieved a significant reduction in liver fat content (LFC), a key secondary endpoint.

The RISE study (NCT05338034) is a multi-center, randomized, double-blind, placebo-controlled, parallel-group, Phase 2a clinical trial to evaluate the safety, tolerability, efficacy, and pharmacokinetics of orally administered HPG1860 tablet at doses of 3 mg, 5 mg and 8 mg in 87 adult patients with presumed non-cirrhotic non-alcoholic steatohepatitis (NASH). The primary objective of the clinical trial was to evaluate the safety and tolerability of HPG1860. Secondary endpoints included percent change from baseline in LFC measured by MRI proton density fat fraction (MRI-PDFF), ALT levels, plasma pharmacokinetics of HPG1860, pharmacodynamic parameters, and serum NASH biomarkers.

In the RISE trial, once daily administration of HPG1860 for 12 weeks was generally well tolerated and most AEs were mild and moderate. Treatment-related pruritus occurred in 9.1%, 9.5%, 27.3% of patients in the 3, 5, and 8mg cohort respectively and no significant change in LDL cholesterol (LDL-C) was observed in the 3 mg, 5 mg and 8 mg HPG1860 cohorts.

Mean relative changes in LFC at week 12 were 0.68% (placebo), -20.15% (3 mg, p=0.002 vs placebo), -7.08% (5 mg, p=0.244 vs placebo), and -38.64% (8 mg, P<0.0001 vs placebo). Relatively reduced efficacy in 5 mg cohort may be due to the lower LFC at baseline vs other cohorts. For patients with ALT ≥ULN at baseline, at week 12, mean ALT percentage change from baseline in placebo, 3 mg, 5 mg and 8 mg cohort was 32.6%, -7.0%, -7.6% and -22.5% respectively, indicating dose-dependent reduction of ALT in HPG1860 treated patients.

Stephen Harrison, MD, Chairman of Summit Clinical Research whose network was responsible for enrolling this study stated, “Positive signals of LFC reduction and improvement in liver chemistry tests, along with a good safety and tolerability profile, make HPG1860 an interesting compound to study further in combination with other mechanisms of action targeting the pathogenic pathways in NASH. LDL elevations are typically seen with FXR agonists so it is encouraging to note that no significant elevations in LDL were seen in this short term trial with HPG1860.”

“We are very encouraged by the significant improvement in LFC and safety profile of HPG1860. I would like to thank those who have supported enrollment in the RISE Study, especially our outstanding investigators and the patients who participated in the study.” said Que Liu MD PhD, Chief Medical Officer of Hepagene, “NASH is a multifactorial liver disease and combination therapy may be needed to achieve clinically meaningful responses and outcomes. We look forward to advancing HPG1860 clinically, including as the key component for future NASH combination treatments.”

Hepagene plans to submit an abstract with detailed data from the RISE Study to an upcoming scientific conference. Based on these positive results, Hepagene continues with the current clinical development plan including a combination trial of HPG1860 with HPG7233, a thyroid hormone receptor beta agonist (THR-β) developed in house for the treatment of NASH.

About HPG1860

HPG1860 is a next generation liver enrichment FXR agonist with a non-bile acid scaffold. Through regulation of gene expression of bile acids, FXR serves as a key controller of bile acid homeostasis. FXR has been studied for its role in modulating inflammation and the expression of FXR is down-regulated during NASH development. HPG1860 exhibited superb efficacy and safety profile in preclinical, Phase 1 and 2a clinical trial.

About NASH

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide, with an approximate prevalence of 20-30% in western countries.  An estimated 20-25% of these patients will further progress to NASH, marked by steatohepatitis, ballooning and inflammation.  Typically, NASH is accompanied with liver fibrosis that can progress to liver cirrhosis and hepatocellular carcinoma. NASH is currently ranked the second most common reason for liver transplants in the USA and is expected to become the leading cause for liver transplant by 2025.

About Hepagene Therapeutics, Inc.

Hepagene Therapeutics, Inc. devotes its efforts towards discovering, developing and delivering innovative medicines that help patients prevail over liver diseases, especially non-alcoholic steatohepatitis (NASH), chronic Hepatitis B infection and rare liver diseases.

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SOURCE: Hepagene Therapeutics