Precision BioSciences Announces Oral Presentation of Positive ARCUS® Gene Editing Data at International Liver Congress 2023
- High antiviral activity with substantial and durable reductions in hepatitis B serum antigen and covalently closed circular DNA in preclinical studies of PBGENE-HBV
- Supports continued PBGENE-HBV development and planned submission of CTA/IND application
DURHAM, N.C.--(BUSINESS WIRE)-- Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company developing ARCUS®-based in vivo gene editing and ex vivo allogeneic CAR T therapies, today announced that the company will present positive preclinical data from its PBGENE-HBV development program for the treatment of patients with chronic hepatitis B during an oral presentation (Abstract #OS-034) Thursday, June 22, 2023 at the European Association for Study of the Liver (EASL) Congress 2023 in Vienna, Austria.
Hepatitis B virus (HBV) causes inflammation and damage to the liver, leading to chronic infection and increased risk of death from liver cancer or cirrhosis. There is no cure for chronic hepatitis B and current treatments rarely result in functional cure, primarily due to persistence of viral DNA in the liver. In patients with chronic HBV, genetic material of the virus is converted within infected liver cells into covalently closed circular DNA (cccDNA) that acts as a template to make HBV copies. HBV also inserts its DNA into the human genome of infected liver cells. This integrated HBV DNA produces the viral protein, hepatitis B surface antigen (HBsAg), which is secreted in the blood. Presence of HBsAg is associated with poorer outcomes and elimination of HBsAg is necessary for functional cure of chronic hepatitis B. Using ARCUS, company scientists generated a highly specific and effective nuclease to eradicate chronic HBV infection. PBGENE-HBV is designed to inactivate cccDNA with direct cuts and edits as well as to inactivate integrated HBV DNA leading to long lasting reductions in HBsAg.
In an episomal adeno-associated virus (AAV) mouse model, company researchers demonstrated that administration of lipid nanoparticles containing mRNA encoding an HBV-targeted ARCUS nuclease resulted in a 96% reduction in serum HBsAg. In a follow-on experiment, treatment of HBV-infected primary human hepatocytes with the HBV-targeted ARCUS nuclease resulted in a 90% reduction of covalently closed circular DNA (cccDNA) and high specificity.
“Even with lifelong administration, the current treatments of chronic HBV rarely achieve a functional cure because they do not eradicate the cccDNA or inactivate the viral DNA that is integrated into the human genome in hepatocytes. Eliminating both the cccDNA and HBsAg are key parameters for achieving a functional cure of HBV,” said Jeff Smith, Co-Founder and Chief Research Officer at Precision Biosciences. “In preclinical models presented at EASL, we’ve demonstrated that administration of HBV-targeted ARCUS nucleases can achieve a near complete reduction in both HBsAg and cccDNA.”
These data continue to highlight the potential of the ARCUS gene editing platform to achieve a functional cure for patients and support continued development of PBGENE-HBV with planned submission of a CTA/IND application.
Title: A Gene Editing Approach for Chronic Hepatitis B: Elimination of Hepatitis B Virus In Vivo by Targeting cccDNA and Integrated Viral Genomes with a Sequence-Specific ARCUS Nuclease
Authors: Gorsuch C, et al.
Date and Time: Thursday, June 22, 2023, 6:15-6:30pm CEST / 12:15-12:30pm EDT
Abstract Number: OS-034
Session Title: Abstract session - Viral hepatitis B/D - New treatments
Session Room: Strauss 2-3
About Hepatitis B and the PBGENE-HBV development candidate:
Hepatitis B is a leading cause of morbidity in the US and death globally, with no curative options currently available for patients. In 2019, despite the availability of approved antiviral therapies, an estimated 300 million people globally and more than 1 million people in the US were estimated to have chronic hepatitis B infection. An estimated 15% to 40% of patients with HBV infections may develop complications, such as cirrhosis, liver failure, or liver cancer (hepatocellular carcinoma), which account for the majority of HBV-related deaths.
Chronic hepatitis B infection is primarily driven by persistence of HBV cccDNA and integration of HBV DNA into the human genome in liver cells, the primary source of HBsAg in late-stage disease. Current treatments for patients with HBV infection include agents that result in long-term viral suppression as indicated by reduction of circulating HBV DNA, but these therapies do not eradicate HBV cccDNA, rarely lead to functional cure, and require lifelong administration. PBGENE-HBV is a highly specific, novel therapeutic approach to treating patients with chronic HBV infection. It’s designed to directly cut and edit cccDNA and inactivate integrated HBV DNA with high specificity, resulting in degraded cccDNA and a reduction in HBsAg.
About Precision BioSciences, Inc.
Precision BioSciences, Inc. is a clinical stage biotechnology company dedicated to improving life (DTIL) with its novel and proprietary ARCUS® genome editing platform. ARCUS is a highly precise and versatile genome editing platform designed with therapeutic safety, delivery, and control in mind. Using ARCUS, the Company’s pipeline consists of several in vivo gene editing candidates designed to cure genetic and infectious diseases where no adequate treatments exist and multiple ex vivo clinical candidates. 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 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 the expected safety, efficacy, and benefit of our gene editing approaches including editing efficiency and delivery methods, the suitability of ARCUS nucleases for gene excision, the clinical development, nomination, and goals of our PBGENE-HBV program, the timing of the submission of a CTA/IND application for PBGENE-HBV, and therapeutic potential of an ARCUS gene editing approach for the treatment of chronic hepatitis B. 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,” “possible,” “potential,” “predict,” “project,” “pursue,” “should,” “target,” “will,” “would,” or the negative thereof and similar words and expressions.
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