– ARCUS genome editing resulted in substantial reductions in both ccc DNA and hepatitis B surface antigen (HBsAg), 85% and 77%, respectively, in human hepatocytes primary (PHH) infected with HBV
– Significant decrease in HBsAg and high on-target editing achieved in novel mouse and non-human primate models following administration of ARCUS mRNA Lipid Nanoparticles (LNPs)
– Circulating HBsAg surface antigen was sustainably reduced by 96% in mice
– Published data also presented at the 2022 Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT)
– Precision will continue to develop the PBGENE-HBV product candidate using LNP delivery and expects to submit an IND/CTA in 2024
DURHAM, NC, May 18, 2022–(BUSINESS WIRE)–Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical-stage gene-editing company developing ex-vivo CAR T allogeneic and live gene-editing therapies, today announced the preclinical research of its live gene-editing program targeting hepatitis B virus (HBV) has been published online in Molecular therapy. The data from this study,Targeting hepatitis B cccDNA with a sequence-specific ARCUS nuclease to eliminate hepatitis B virus in vivo“support the company’s continued development of its candidate PBGENE-HBV as a promising gene-editing approach that aims to eliminate virus persistence by targeting covalently closed circular DNA (cccDNA) in patients with chronic hepatitis B. This study was conducted in collaboration with Gilead Sciences and Acuitas Therapeutics and was also presented this week during the oral session on gene editing in cancer and complex diseases at the annual meeting of the ‘ASGCT.
“We are very pleased to see this study published in Molecular therapy and to present the compelling reductions in cccDNA and surface antigen achieved with our ARCUS gene-editing platform in two novel animal models of HBV infection. Our data suggest that LNP-delivered ARCUS mRNA merits further exploration as a possible functional treatment for chronic hepatitis B,” said Derek Jantz, Chief Scientific Officer and Co-Founder of Precision BioSciences.
Precision’s gene-editing program for chronic hepatitis B is designed to apply ARCUS to eliminate persistent cccDNA and inactivate integrated hepatitis B genomes, which could lead to lasting loss of HBsAg and functional cure. In this preclinical study, ARCUS effectively targeted and degraded HBV cccDNA by 85% and reduced HBsAg expression by 77% in HBV-infected PHHs. Importantly, the optimized specificity of the ARCUS nuclease completely prevented detectable chromosomal translocations in the PHH model.
To evaluate ARCUS live, new mouse and non-human primate models were developed that used an episomal adeno-associated virus (AAV) containing part of the HBV genome as a surrogate for cccDNA. Following administration of LNP containing ARCUS mRNA, high on-target editing and a robust downregulation of cccDNA surrogate were observed in both episomal models, along with a sustained 96% reduction in l 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 the cccDNA, there is always the potential that the virus could reactivate,” continued Cassandra Gorsuch, Ph.D., head of Gene Therapy at Precision BioSciences and lead author of the paper. “Current standard treatments for chronic hepatitis B work by lowering or eliminating the amount of HBV found in infected cells in the body, but have no direct impact on the presence of cccDNA, and therefore rarely completely eliminate the virus, requiring life-long therapy.”
Accuracy live The development pipeline currently includes six novel product candidates for genetic diseases. Three of these product candidates are 100% owned – PBGENE-HBV for chronic hepatitis B, PBGENE-PH1 for primary hyperoxaluria type 1, and PBGENE-PCSK9 for familial hypercholesterolemia – and Precision plans to progress them to IND or CTA over the next three years.
About Precision BioSciences, Inc.
Precision BioSciences, Inc. is a clinical-stage biotechnology company dedicated to improving lives (DTIL) with its new proprietary ARCUS genome editing platform. ARCUS is a highly accurate and versatile genome editing platform that was designed with therapeutic safety, delivery and control in mind. Thanks to ARCUS, the Company’s pipeline consists of several ex-vivo “Ready-to-use” CAR T immunotherapy clinical candidates and several live gene-editing candidates designed to cure genetic and infectious diseases where adequate treatments do not exist. For more information about Precision BioSciences, please visit www.precisionbiosciences.com.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements in this press release that do not relate to historical facts should be considered forward-looking statements, including, without limitation, statements regarding the targeting of hepatitis B cccDNA with ARCUS nucleases in novel animal models. In some cases, you can identify forward-looking statements by words such as “aim”, “anticipate”, “approach”, “believe”, “intend”, “could”, “estimate”, “expect”. to”, “goal”, “intend”, “look”, “may”, “mission”, “plan”, “potential”, “predict”, “project”, “should”, “target” , “will”, “should” or the negative thereof and similar words and expressions.
Forward-looking statements are based on management’s current expectations, beliefs and assumptions and information currently available to us. These 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 by the forward-looking statements due to a variety of important factors, including, but not limited to: our ability to become profitable; our ability to obtain sufficient funding and requirements under our current debt instruments and the 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 reliance 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 of genome editing technology and its applications; competition in the fields of genome editing, biopharmaceuticals and biotechnology; our ability or that of our collaborators to identify, develop and commercialize product candidates; pending and potential liability lawsuits and sanctions against us or our collaborators related to our technology and product candidates; the U.S. and foreign regulatory landscape applicable to our and our collaborators’ development of product candidates; our ability or that of our collaborators to obtain and maintain regulatory approval for our product candidates, and any related restrictions, limitations and/or warnings on the label of an approved product candidate; our ability or that of our collaborators to advance product candidates and to design, implement and complete clinical or field trials; potential manufacturing issues associated with the development or commercialization of any of our product candidates; our ability to obtain an adequate supply of T cells from qualified donors; our ability to achieve our expected operating efficiencies at our manufacturing facility; delays or difficulties in our ability and that of our associates to recruit patients; changes in intermediate top-lines and initial data that we announce or publish; if our product candidates fail to perform as expected or cause adverse side effects; risks associated with applicable healthcare, data protection, privacy and security regulations and our compliance therewith; the rate and degree of market acceptance of any of our product candidates; the success of our existing collaboration agreements and our ability to enter into new collaboration agreements; our current and future relationships with third parties and our dependence on third parties, including suppliers and manufacturers; our ability to obtain and maintain intellectual property protection for our technology and any of our product candidates; potential litigation related to infringement or misappropriation of intellectual property rights; our ability to effectively manage the growth of our operations; our ability to attract, retain and motivate key executives and personnel; market and economic conditions; the effects of system failures and security breaches; the effects of natural and man-made disasters, public health emergencies and other catastrophic natural events; effects of the COVID-19 pandemic and its variants, or any pandemic, epidemic or outbreak of an infectious disease; insurance expenses and exposure to uninsured liabilities; effects of tax rules; risks relating to ownership of our common stock and other important factors discussed under “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2021, as such factors may be updated from time to time in our other filings with the SEC, including, but not limited to, our Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2022, filing with the SEC , which can be accessed on the SEC’s website at www.sec.gov and the Investors page of our website under SEC Filings at investor.precisionbiosciences.com.
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