Precision BioSciences Announces Preclinical Data Showcasing Premier In Vivo Gene Editing Capabilities at American Society of Gene & Cell Therapy Annual Meeting
Multiple Oral Presentations and Posters to Demonstrate Differentiated Attributes of ARCUS® Genome Editing Platform for Efficient Gene Insertion and Gene Knockout
New Primary Hyperoxaluria Type 1 (PH1) Preclinical Data Demonstrate a Robust ARCUS Nuclease Optimization Process Leading to 98% Knockdown of HAO1 Protein in Non-human Primates (NHP)
“The preclinical findings presented this week at the ASGCT conference are very encouraging and further support our novel gene editing approach with ARCUS and our plans to advance three wholly owned product candidates, PBGENE-PH1, PBGENE-HBV and PBGENE-PCSK9, to the clinic over the next three years,” said
Abstract #447: Targeting the Hepatitis B cccDNA with a Sequence-Specific ARCUS Nuclease to Eliminate Hepatitis B Virus In Vivo
Data from this preclinical study demonstrate Precision’s gene editing approach designed to eliminate hepatitis B virus (HBV). ARCUS efficiently targeted and degraded HBV covalently closed circular (cccDNA) by 85% and reduced expression of Hepatitis B Surface Antigen (HBsAg) by 77% in HBV-infected primary human hepatocytes (PHH). Similar levels of editing were achieved in novel mouse and NHP models following lipid nanoparticle (LNP) delivery of ARCUS mRNA, resulting in a 96% reduction in HBsAg in mice. These data suggest that LNP-delivered ARCUS mRNA is a promising approach and potential functional cure for chronic hepatitis B. Precision will continue developing its PBGENE-HBV product candidate using LNP delivery and expects to submit an IND/CTA in 2024.
Abstract #811, Presidential Symposium and Presentation of Top Abstracts: AAV-Meganuclease-Mediated Gene Targeting Achieves Efficient and Sustained Transduction in Newborn and Infant Macaque Liver1
Preclinical data will be presented during the Presidential Symposium and highlight an ARCUS-based gene insertion approach for the treatment of ornithine transcarbamylase (OTC) deficiency. This strategy was informed by previous work in adult NHPs, which showed safe, efficient and stable reductions of PCSK9 following adeno associated virus (AAV) delivery of an ARCUS nuclease. In this study, therapeutically meaningful and stable levels of OTC expression were observed in NHPs. Treatment was well-tolerated in all animals, showing no evidence of transaminase elevations or liver histopathology in any ARCUS-treated animals. Preliminary data suggests that the level of editing is stable over one year. Together, these data demonstrate preclinical feasibility of using an ARCUS-mediated gene insertion approach for the treatment of OTC deficiency.
Abstract #239: Optimization of Hydroxyacid Oxidase 1 (HAO1) Targeting ARCUS Nucleases for the Treatment of Primary Hyperoxaluria Type 1 (PH1)
Preclinical data presented in this poster demonstrate HAO1-targeting and optimization of ARCUS nucleases delivered via AAV in NHPs. A single infusion of AAVs carrying first generation HAO1-targeting nucleases resulted in >95% knockdown of HAO1 protein in NHP liver and increases in serum glycolate up to 80µM. ARCUS nuclease optimization through iterative rounds of protein engineering resulted in improvements in both potency and specificity of HAO nucleases. These data demonstrate the ability to optimize ARCUS nucleases to specifically target the HAO1 gene to control the glyoxylate metabolic pathway responsible for PH1. Precision has initiated a NHP study for PBGENE-PH1 delivered by LNP and expects to submit an IND or CTA in 2023.
Abstract # 561: ARCUS Gene Editing to Eliminate MELAS-associated m.3243A>G Mutant Mitochondrial DNA2
Preclinical data presented in this poster demonstrate Precision’s gene editing approach to shift mitochondrial DNA (mtDNA) heteroplasmy for the m.3243A>G mtDNA mutation. This mutation resides in mitochondrial tRNA and is responsible for >80% of cases of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). This study found that mitoARCUS was successfully trafficked to the mitochondria and, once there, specifically cleaved and eliminated m.3243G mutant mtDNA without impacting wild-type (WT) mtDNA. This resulted in preferential replication of WT mtDNA, and, consequently, improvements in mitochondrial function. Precision BioSciences’ protein engineering and optimization platform allowed for the generation of highly specific nucleases that accurately discriminated between WT and mutant mtDNA despite only a single nucleotide difference. Together, these data showcase the promise of ARCUS as a potential in vivo gene editing approach for the treatment of disease-causing heteroplasmic mtDNA mutations.
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 our preclinical studies, including targeting hepatitis B cccDNA with ARCUS nucleases in novel animal models, ARCUS-based gene insertion approach for the treatment of OTC deficiency, HAO1-targeting and optimization of ARCUS nucleases, the expected timing of future IND and CTA filings, and expected IND updates and advancement of preclinical programs to IND or CTA. 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,” “promising,” “should,” “suggest,” “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
All forward-looking statements speak only as of the date of this press release and, except as required by applicable law, we have no obligation to update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.
1 University of Pennsylvania’s Gene Therapy Program oral presentation sponsored by iECURE
2 Research conducted in collaboration with the
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