EDP-721

EDP-721 is an investigational small molecule drug developed by Enanta Pharmaceuticals for the treatment of chronic hepatitis B virus (HBV) infection. It acts as a potent and selective oral inhibitor of the non-canonical poly(A) polymerases PAPD5 and PAPD7, which are host factors critical to the post-transcriptional stabilization of HBV RNA. By inhibiting these enzymes, EDP-721 destabilizes HBV RNAs, leading to reduced production of viral proteins including HBsAg (hepatitis B surface antigen), HBcAg, and HBeAg. The compound demonstrated pangenotypic activity against all tested HBV genotypes (A-H), with minimal effects on host transcriptome in uninfected primary human hepatocytes. Preclinical studies showed significant reductions in HBsAg levels and additive or synergistic antiviral effects when combined with nucleos(t)ide reverse transcriptase inhibitors or core inhibitors such as EDP-514. Despite promising preclinical results, clinical development was discontinued following safety concerns identified during early-phase trials[1][2][3][4][5][6][8].