Hepagene Therapeutics, Inc. Announces Positive Results from Phase I Trial of HPG1860

ETC

SHANGHAI, Aug. 23, 2021 /PRNewswire/ — Hepagene Therapeutics, Inc., a clinical stage biopharmaceutical company focusing on novel therapies for patients with liver diseases, today announced positive results from its Phase I study of HPG1860 conducted in the United States. HPG1860 is a non-bile acid, potent, selective and full FXR agonist being developed for treatment of non-alcoholic steatohepatitis (NASH) and primary biliary cholangitis (PBC). Findings show that treatment with HPG1860 was safe, well-tolerated and demonstrated a robust target engagement with a favorable pharmacokinetic (PK) profile after 14 days of once daily dosing in healthy volunteers. Detailed results will be presented at upcoming AASLD international liver conference.

The Hepagene phase I trial was a first-in-human, randomized, placebo-controlled, double-blind single-ascending dose (SAD) and multiple-ascending dose (MAD) trial, in which healthy volunteers received once-daily HPG1860 doses ranging from 10 mg to 100 mg in the SAD cohorts and 5 mg to 20 mg in the MAD cohorts for 14 days. The primary objective of the trial was to evaluate safety/tolerability and the secondary objectives were to assess PK parameters and FXR target engagement, the latter through measurement of fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4), blood biomarkers of bile acid synthesis and metabolic homeostasis that increases and decreases respectively with FXR activation.

HPG1860 was safe and generally well-tolerated with no serious adverse events reported. Most adverse events were mild in severity.  Importantly, pruritus only occurred in highest dose cohort (20 mg) and LDL-cholesterol increases were not seen at any dose level. HPG1860 exhibited a favorable PK profile as well as robust FXR target engagement with notable C4 regression – 93.1%, 97.0% and 97.6% decrease observed after the last dose in MAD 5 mg, 10 mg and 20 mg cohorts compared with placebo. The magnitude of C4 decrease can be used to project potential liver fat reduction level in NASH patients, with ≥ 30% relative liver fat reduction being associated with increased likelihood of histological benefits upon liver biopsy.

"We are encouraged by the overall safety profile of HPG1860, and meaningful target engagement seen at as low as the 5 mg dose level. We plan to evaluate the 3 mg, 5mg and 8 mg dose levels in our upcoming Phase IIa trial in NASH patients," said Que Liu, M.D., PhD, Chief Medical Officer of
Hepagene.

"It is encouraging to see that there was no significant increase in LDL cholesterol despite excellent FXR target engagement with sustained C4 suppression." said Rohit Loomba, MD, MHSc, Professor of Medicine, and Director, UCSD NAFLD Research Center, University of California at San Diego, La Jolla, CA.

"NASH is a complex liver disease with multiple pathways involved in liver cell injury, inflammation and fibrosis development. FXRs have been shown to impact the underlying pathology of NASH in a meaningful way. Combination therapy, involving multiple mechanisms of action, is likely going to be needed to combat this disease effectively, providing an opportunity for HPG1860. The early data presented here are very encouraging from a safety and tolerability perspective and I am looking forward to beginning the phase 2 study." said Stephen Harrison, MD, Medical Director of Pinnacle Clinical Research in San Antonio, Texas.

Based on the Phase 1 safety and PK/PD data, Hepagene plans to advance three dose levels of HPG1860 3 mg, 5 mg and 8 mg in a 12-week, randomized, placebo-controlled Phase IIa trial enrolling about 80 patients with NASH in US. The selected doses are projected to inhibit C4 to levels that are likely to result in meaningful reductions in liver fat content. The trial is scheduled to start in the last quarter of 2021, with an interim analysis planned in the first half of 2022.

About HPG1860

HPG1860 is an investigational potent and selective full FXR agonist with a non-bile acid scaffold and is currently in first-in-human clinical phase I study. 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 research.

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.

About Hepagene Therapeutics, Inc.

Hepagene Therapeutics, Inc. devotes its drug discovery and development 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 liver cancer.

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