The Discovery and Preclinical Profile of ALG-000184, a Prodrug of the Potent Hepatitis B Virus Capsid Assembly Modulator ALG-001075

Chronic hepatitis B (CHB) represents a significant unmet
medical
need with few options beyond lifelong treatment with nucleoside analogues,
which rarely leads to a functional cure. Novel agents that reduce
levels of HBV DNA, RNA and other viral antigens could lead to better
treatment outcomes. The capsid assembly modulator (CAM) class of compounds
represents an important modality for chronic suppression and to improve
functional cure rates, either alone or in combination. GLP-26 is a potent CAM, which in this work was optimized for potency, safety,
and other drug-like properties leading to ALG-001075. ALG-001075 was further advanced through clinical development
as the highly soluble prodrug ALG-000184. ALG-000184 is currently being explored in multiple clinical trials in HBV-infected
subjects where unprecedented reductions in HBV DNA, RNA and other
viral antigens have been observed, making ALG-000184 a
promising candidate to become a cornerstone for future chronic suppressive
and combination treatment regimens for CHB.