Assembly Biosciences, Inc. announced that results from a research study evaluating the turnover rate of covalently closed circular DNA (cccDNA), which plays a pivotal role in the establishment and persistence of HBV infection, has been published in Hepatology, the journal of the American Association for the Study of Liver Diseases (AASLD). The study was led by Qi Huang, PhD, the Company’s Vice President of Virology Discovery, and was conducted in collaboration with Professors Jinlin Hou, Jian Sun, and Bin Zhou of Nanfang Hospital, Southern Medical University in Guangzhou, China. The article is entitled Rapid Turnover of HBV cccDNA Indicated by Monitoring Emergence and Reversion of Signature-Mutation in Treated Chronic Hepatitis B Patients and is available online with open access. Understanding the turnover time of the intranuclear preexisting cccDNA pool is important in evaluating and assessing potential curative treatment regimens for chronic HBV infection. This study used a molecular genetic approach to monitor the appearance and disappearance of resistance mutations as a biomarker of cccDNA turnover in longitudinal liver biopsies and serum samples obtained from patients from two clinical trials. HBV virion DNA, cccDNA, and HBV pgRNA were isolated and sequenced from clinical samples. The genetic makeup of cccDNA pools were shown to turnover in as little as three to four months, consistent with frequent cccDNA replacement in chronically-infected patients and suggesting that regimens which fully inhibit cccDNA replenishment may achieve a finite cure through decay of the existing cccDNA pool during treatment. Further, a strong correlation was observed between cccDNA composition and serum pgRNA in paired liver and serum samples, suggesting that serum HBV pgRNA is a primary surrogate marker of cccDNA when liver biopsies are unavailable. Assembly’s HBV portfolio includes several clinical-stage small molecules, all of which are inhibitors of the HBV core protein targeting multiple steps of the life cycle of HBV. ABI-H0731, a first-generation core inhibitor, is advancing in Phase 2 clinical development. In Phase 2 clinical trials, ABI-H0731 administered with nucleos(t)ide therapy has been well-tolerated and has shown statistically superior antiviral activity in HBV DNA suppression compared to nucleos(t)ide therapy alone and also significant declines in pgRNA that may indicate decreases in cccDNA levels. Assembly’s HBV portfolio also includes two clinical-stage second-generation candidates ABI-H2158 and ABI-3733.