Assembly Biosciences Present Data Highlighting Next-Generation HBV Core Protein

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https://investor.assemblybio.c（om/

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cccDNA Turnover Study– Poster Presentation
Rapid Turnover of HBV cccDNA in Nucleoside-Treated Chronic Hepatitis B Patients During Drug Resistance Emergence and Breakthrough
The current low cure rates for HBV infection on standard of care nucleos(t)ide (Nuc) therapy are believed to be due to an inability to eliminate residual viral replication. As a result, generation of new cccDNA persists despite prolonged therapy. Initial mathematic modeling studies, built on the premise that Nucs effectively blocked new cccDNA formation, estimated that it could take at least 14 years to clear intrahepatic cccDNA from a chronically-infected HBV patient. Using a molecular genetics approach that monitored the emergence and disappearance of Nuc resistance mutations as a genetic marker of cccDNA, Assembly has revisited the question of cccDNA turnover. Evaluations were conducted with patient derived longitudinal liver and serum samples (paired) from two historical clinical studies. In these studies, cccDNA population turnover from sensitive to resistant or from resistant to sensitive occurred in as little as 12-17 weeks, suggesting relatively rapid turnover of cccDNA pools and/or infected cells. This study indicates that existing cccDNA has a limited half-life, suggesting that therapies inhibiting establishment of new cccDNA may lead to higher cure rates for patients with HBV.