At the ICE-HBV Cure Symposium, EBT-107 showed reduced intrahepatic HBV DNA and no increase in chromosomal translocations, supporting a path toward first-in-human testing.
Excision Reports EBT-107 Reduces HBV Load and Prevents De Novo Integration Preclinically
Image credits: Excision
Excision BioTherapeutics reported new preclinical results for its hepatitis B virus (HBV) gene-editing candidate EBT-107, showing reductions in intrahepatic HBV DNA and suppression of de novo HBV DNA integration in HBV-infected primary human hepatocytes and in two chronic HBV mouse models. Deep-sequencing analyses found no increase in overall integration and no differences in chromosomal translocations compared with controls. The company said these data support advancing EBT-107 toward first-in-human studies, noting that current antivirals reduce viral load but do not eliminate cccDNA, the reservoir that enables persistent infection.1
In the press release, CEO Daniel Dornbusch said in vitro and in vivo studies indicate the dual guide RNA editing strategy can eliminate intrahepatic HBV DNA molecules while suppressing integration that may contribute to hepatocarcinogenesis, and that safety signals remain favorable, with fragmentation of episomal HBV DNA not increasing host-genome integration or chromosomal rearrangements in treated liver samples.¹ Clinical efficacy has not yet been established.1
EBT-107 reduced intrahepatic HBV DNA and suppressed de novo integration in HBV-infected primary human hepatocytes and two chronic HBV mouse models.
Deep sequencing found no increase in overall integration or chromosomal translocations compared with controls.
The dual-guide CRISPR approach targets cccDNA that current antivirals do not eliminate, with clinical studies planned.
Prior data presented at the 2024 International HBV Meeting in Chicago last September, Excision reported that the nanoparticle-delivered, dual-guide version of EBT-107 suppressed HBV biomarkers in vitro and in vivo, providing a rationale for clinical development.2
For context, HBV DNA integration, once considered a byproduct, is now recognized as a driver of pathogenesis and hepatocarcinogenesis. Integrated sequences can produce HBsAg and HBx, promote chromosomal instability, and sustain disease activity even when replication is low, complicating cure endpoints based on HBsAg loss and supporting HDV persistence. These biology insights frame Excision’s preclinical claim of suppressing new integration events.3
The new results add a mechanistic and safety context around EBT-107’s dual-guide CRISPR approach targeting HBV DNA and cccDNA-dependent persistence. The next milestone is translation to human studies to determine whether these preclinical signals produce meaningful clinical benefit.
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