AB-452

**AB-452** is a potent, highly selective small molecule HBV RNA destabilizer developed by Arbutus Biopharma for chronic hepatitis B virus (HBV) infection. It inhibits non-canonical RNA polymerases **PAPD5** and **PAPD7**, leading to destabilization of HBV RNA, significant reductions in viral RNA levels, HBsAg, and other antigens (EC50 1.5 nM in HepG2.2.15 cells), pan-genotypic activity, and no cross-resistance with nucleoside analogs. Orally bioavailable with strong preclinical efficacy in mouse models, it showed additive to synergistic effects in combinations with capsids inhibitors like AB-506 and NAs like TDF/TAF, but was terminated due to peripheral neurotoxicity in long-term dog studies.[1][3][5][6]