Precision BioSciences Announces Publication in Molecular Therapy of ARCUS® In Vivo Gene Editing as a Promising Therapeutic Approach to Cure Chronic Hepatitis B Infection
- ARCUS Genome Editing Achieved Substantial Reductions in both cccDNA and Hepatitis B Surface Antigen (HBsAg), 85% and 77% respectively, in HBV-infected Primary Human Hepatocytes (PHH)
- Significant Decrease in HBsAg and High On-target Editing Achieved in Novel Mouse and Non-human Primate Models Following Lipid Nanoparticle (LNP) Delivery of ARCUS mRNA
- Circulating HBsAg Surface Antigen was Durably Decreased by 96% in Mice
- Data Published also Presented at the 2022
- Precision to Continue Developing PBGENE-HBV Product Candidate Using LNP Delivery and Expects to Submit an IND/CTA in 2024
“We’re very excited to see this study published in Molecular Therapy and to showcase the compelling reductions in cccDNA and surface antigen obtained with our ARCUS gene editing platform in two novel animal models of HBV infection. Our data suggest that LNP-delivered ARCUS mRNA is worth further exploration as a possible functional cure for chronic hepatitis B,” said
Precision’s gene editing program for chronic hepatitis B is designed to apply ARCUS to knock out persistent cccDNA and inactivate integrated hepatitis B genomes, potentially achieving durable HBsAg loss and functional cure. In this preclinical study, ARCUS efficiently targeted and degraded HBV cccDNA by 85% and reduced expression of HBsAg by 77% in HBV-infected PHH. Importantly, the optimized specificity of the ARCUS nuclease completely prevented detectable chromosomal translocations in the PHH model.
To evaluate ARCUS in vivo, novel mouse and non-human primate models were developed that utilized an episomal adeno-associated virus (AAV) containing a portion of the HBV genome to serve as a surrogate for cccDNA. After administration of LNP containing ARCUS mRNA, high on-target editing and a robust decrease in the cccDNA surrogate was observed in both episomal models, along with a durable 96% reduction of HBsAg in mice.
“The real challenge with HBV is that it persists in chronically infected hepatocytes as an extrachromosomal genome called cccDNA. Unless we can eliminate cccDNA, there’s always the potential that the virus can reactivate,” continued
Precision’s in vivo development pipeline currently comprises six novel product candidates for genetic diseases. Three of these product candidates are wholly owned -- PBGENE-HBV for chronic hepatitis B, PBGENE-PH1 for primary hyperoxaluria type 1 and PBGENE-PCSK9 for familial hypercholesteremia -- and Precision expects to advance them to IND or CTA over the next three years.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding targeting hepatitis B cccDNA with ARCUS nucleases in novel animal models. In some cases, you can identify forward-looking statements by terms such as “aim,” “anticipate,” “approach,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “goal,” “intend,” “look,” “may,” “mission,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would,” or the negative thereof and similar words and expressions.
Forward-looking statements are based on management’s current expectations, beliefs and assumptions and on information currently available to us. Such statements are subject to a number of known and unknown risks, uncertainties and assumptions, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various important factors, including, but not limited to: our ability to become profitable; our ability to procure sufficient funding and requirements under our current debt instruments and effects of restrictions thereunder; risks associated with raising additional capital; our operating expenses and our ability to predict what those expenses will be; our limited operating history; the success of our programs and product candidates in which we expend our resources; our limited ability or inability to assess the safety and efficacy of our product candidates; our dependence on our ARCUS technology; the initiation, cost, timing, progress, achievement of milestones and results of research and development activities, preclinical studies and clinical trials; public perception about genome editing technology and its applications; competition in the genome editing, biopharmaceutical, and biotechnology fields; our or our collaborators’ ability to identify, develop and commercialize product candidates; pending and potential liability lawsuits and penalties against us or our collaborators related to our technology and our product candidates; the
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Senior Director, Corporate Communications