Benzinga | Aug 16, 2021 07:03AM EDT

Enanta Pharmaceuticals Doses First Subject in a Phase 1 Clinical Study of EDP-721, Its Oral Hepatitis B Virus RNA Destabilizer

Enanta Pharmaceuticals, Inc., (NASDAQ:ENTA), a clinical stage biotechnology company dedicated to creating small molecule drugs for viral infections and liver diseases, today announced that it has dosed the first subject in its Phase 1 clinical trial of EDP-721, a novel, oral hepatitis B virus (HBV) RNA destabilizer being developed for use in an all-oral combination regimen for chronic HBV patients.

"We are pleased to advance our HBV program by dosing the first subject in our Phase 1 clinical study of EDP-721, an orally administered HBV RNA destabilizer that has the potential to reduce S antigen. As we believe that achieving a functional cure for HBV will involve a combination approach, this milestone brings us closer to our vision of developing an all-oral regimen for HBV," said Jay R. Luly, Ph.D., President and Chief Executive Officer of Enanta Pharmaceuticals. "The current standard of care for chronic HBV involves nucleoside reverse transcriptase inhibitors, or NUCs, which can suppress HBV replication. In addition, EDP-514, our potent core inhibitor inhibits several stages of HBV replication, from uncoating and nuclear import of the virus, to capsid assembly and recycling. Now, with EDP-721, we have an oral compound that has demonstrated preclinically the ability to destabilize HBV RNAs, leading to a reduction in viral proteins, including S antigen, which we believe is essential for the treatment of HBV. With this triple combination of a NUC, EDP-514, and EDP-721, we see the potential for an all-oral functional cure and look forward to progressing this study."

This two-part Phase 1a/b study will initially evaluate the safety, tolerability, and pharmacokinetics of EDP-721 in single and multiple ascending oral doses in healthy volunteers. The second part, in chronic HBV patients, will evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of multiple ascending oral doses of EDP-721 with or without a NUC, and then in combination with EDP-514. Data from the first part of the study are expected in the first half of 2022.

In a recent poster presentation at the European Association for the Study of the Liver (EASL) Digital International Liver Congress(tm) 2021, EDP-721 was shown to be a selective inhibitor of the non-canonical poly(A) polymerases, PAPD5 and PAPD7, which are host factors critical to the post-transcriptional stabilization of HBV RNA. Inhibition of PAPD5/7 results in potent and pangenotypic reduction in HBsAg production with minimal effects on the host transcriptome in uninfected primary human hepatocytes. Oral administration of EDP-721 demonstrated HBsAg reductions of up to 3 log10 IU/mL following 14 days of once-daily dosing in the AAV-HBV mouse model. EDP-721 was also shown to exhibit synergistic antiviral activity in vitro when combined with nucleos(t)ide reverse transcriptase inhibitors or the HBV core inhibitor EDP-514.