Research by Assembly Biosciences and Academic Collaborators Published in Hepatology Indicates cccDNA Turnover Time May Enable Hepatitis B Cures Following Finite Therapy
“This important translational research study provides us with valuable insight as we and others work to advance potential curative therapeutic regimens for patients with HBV infection,” said
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.
About Assembly Biosciences’ HBV Core Inhibitor Portfolio
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.
About Assembly Biosciences
The information in this press release contains forward-looking statements regarding future events, including statements about the therapeutic potential of our HBV core inhibitor product candidates, predictions on the turnover time of preexisting cccDNA pools, and the timing of the initiation of and the availability of data from our ongoing and planned clinical trials. Certain forward-looking statements may be identified by reference to a future period or by use of forward-looking terminology such as “intend,” “may,” “potential,” “promise,” and “strategy.”
Assembly intends such forward-looking statements to be covered by the safe harbor provisions contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. These risks and uncertainties include, among others: the components, timing, cost and results of clinical trials and other development activities involving our product candidates; the impact of the coronavirus pandemic on planned and on-going clinical trials, and results of earlier preclinical and nonclinical studies may not be predictive of future clinical studies results. More information about the risks and uncertainties faced by Assembly are more fully detailed under the heading “Risk Factors” in Assembly’s Annual Report on Form 10-K for the year ended
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Source: Assembly Biosciences, Inc.