• OTC Deficiency Gene Insertion Program, ECUR-506, Receives Clearance from Australian Therapeutic Goods Administration for Phase 1/2 Study

DURHAM, N.C. / Dec 13, 2023 / Business Wire / Precision BioSciences, Inc. (Nasdaq: DTIL), an advanced gene editing company utilizing its novel proprietary ARCUS® platform to develop in vivo gene editing therapies for sophisticated gene edits, including gene insertion, excision, and elimination, today announced that its partner iECURE has received approval from the Australian Therapeutic Goods Administration for the initiation of a first-in-human Phase 1/2 trial evaluating ECUR-506, incorporating an ARCUS nuclease for the treatment of Ornithine Transcarbamylase (OTC) deficiency in pediatric (or neonatal) patients.

“The acceptance of iECURE’s Clinical Trial Application marks an important milestone for patients with OTC deficiency and for both the iECURE and Precision BioSciences teams. This is the first ARCUS in vivo gene editing program to progress into the clinic,” said Michael Amoroso, Chief Executive Officer of Precision Biosciences. “We look forward to supporting iECURE's continued progress with this program while working expeditiously to advance our wholly-owned hepatitis B virus program towards an anticipated clinical trial application (CTA) and/or investigational new drug (IND) filing in 2024.”

OTC deficiency, the most common urea cycle disorder, is an inherited metabolic disorder caused by a genetic defect in a liver enzyme responsible for the detoxification of ammonia. Individuals with OTC deficiency can build up excessive levels of ammonia in their blood potentially resulting in devastating consequences, including irreversible neurological damage, coma and death. The severe form of the condition emerges shortly after birth and is more common in boys than girls. The only corrective treatment for early onset severe OTC deficiency is a liver transplant. Currently available medical therapies do not correct the disease and do not eliminate the risk of life-threatening symptoms or crises.

In preclinical studies, administration of ECUR-506 resulted in a durable response in nonhuman primates, with up to 28.2% of liver cells demonstrating expression of the human OTC gene at the 1-year time point. A 5% threshold of enzymatic activity has the potential for clinical benefit as previously identified in Annals of Clinical and Translational Neurology. Separately, in a mouse model of OTC-deficiency, the injection of ECUR-506 in newborn mice efficiently inserted a healthy copy of the OTC gene.

“At Precision, we have taken a methodical approach in the development, optimization, and validation of ARCUS as a differentiated tool that is uniquely suited for high efficiency gene insertion due to its unique cut which drives homology directed repair (HDR). As presented in preclinical work at the European Society of Gene & Cell Therapy (ESGCT) 30th Annual Congress earlier this year, current ARCUS nucleases demonstrated 17 times higher gene insertion efficiency in primary human T-cells compared to CRISPR-Cas9. In addition, ARCUS showed up to approximately 45% insertion when administered by lipid nanoparticle along with an adeno-associated virus carrying a gene insertion template in adult non-human primates, and demonstrated high efficiency gene insertion via HDR in nondividing, primary human hepatocytes. Today’s announcement of a regulatory clearance for human clinical trials further validates our ARCUS approach and highlights its potential to deliver a curative treatment for patients with OTC deficiency,” said Jeff Smith, Ph.D., Chief Research Officer at Precision BioSciences. “ECUR-506 is the first of several partnered and wholly owned gene editing programs leveraging ARCUS in differentiated indications and we look forward to initial clinical data from this program.”

About Precision BioSciences, Inc.

Precision BioSciences, Inc. is an advanced gene editing company dedicated to improving life (DTIL) with its novel and proprietary ARCUS® genome editing platform that differs from other technologies in the way it cuts, its smaller size, and its simpler structure. Key capabilities and differentiating characteristics may enable ARCUS nucleases to drive more intended, defined therapeutic outcomes. Using ARCUS, the Company’s pipeline is comprised of in vivo gene editing candidates designed to deliver lasting cures for the broadest range of genetic and infectious diseases where no adequate treatments exist. For more information about Precision BioSciences, please visit www.precisionbiosciences.com.

About iECURE

iECURE is a gene editing company focused on developing therapies that utilize mutation-agnostic in vivo gene insertion, or knock-in, editing for the treatment of liver disorders with significant unmet need. iECURE’s approach has the potential to replace and restore the function of a dysfunctional gene, regardless of mutation, by knocking-in a healthy copy of that gene to offer durable gene expression and long-term, potentially curative, therapeutic benefit. iECURE is collaborating with the University of Pennsylvania’s Gene Therapy Program (GTP) led by James M. Wilson, M.D., Ph.D., to utilize GTP’s world-class translational expertise and infrastructure. For more information, visit iecure.com.

Forward-Looking Statements

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 potential of an ARCUS gene editing approach as a curative treatment for OTC deficiency, including durability of response, anticipated timing of a CTA and/or IND filing for wholly-owned programs, the ability and differentiation of ARCUS for high efficiency gene insertion and driving homology directed repair, expected safety, efficacy, and benefit of our gene editing approaches, and anticipated timing of initial clinical data. 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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