AB-506

AB-506 is a **potent, oral, small-molecule inhibitor of the hepatitis B virus (HBV) core protein**, specifically designed as a **pan-genotypic capsid inhibitor**. By binding to the core protein, AB-506 **accelerates formation of empty capsids, inhibits the encapsidation of HBV pregenomic RNA (pgRNA), reduces relaxed circular DNA (rcDNA) production, and prevents the establishment of new covalently closed circular DNA (cccDNA)**, thus disrupting the HBV replication cycle[1][4]. AB-506 displayed activity across HBV genotypes and efficacy against nucleos(t)ide analog-resistant HBV variants in vitro and in animal models[4]. In early clinical trials in healthy volunteers and chronic hepatitis B (CHB) patients, AB-506 led to **dose-dependent reductions in HBV DNA**, but was associated with **severe hepatotoxicity and Grade 4 elevations in liver transaminases** (ALT), particularly in Asian subjects[1][11]. Due to these safety concerns, especially serious transaminitis, all clinical development of AB-506 was **terminated**[1][3][6][9]. The compound was developed and evaluated by **Arbutus Biopharma**[3][11].