Ornithine Carbamoyltransferase Deficiency Disease

4月4日，临床阶段的基因编辑公司iECURE宣布，FDA已批准其领先项目ECUR-506治疗鸟氨酸氨甲酰转移酶（Ornithine Transcarbamylase, OTC）缺乏症的IND申请。ECUR-506将在OTC-HOPE研究中进行评估，用于治疗新生儿OTC缺乏症患者。iECUR目前聚焦治疗罕见儿科肝脏疾病的体内基因插入疗法（gene insertion therapies）。ECUR-506由宾夕法尼亚大学的James M. Wilson教授实验室开发，由递送不同载荷的两个AAV载体组成，一个载体递送ARCUS®核酸酶，目标是在已充分表征的PCSK9基因位点上进行基因编辑；另一个载体负责递送所需的功能性OTC基因（PCSK9上的切割位点作为OTC基因的插入位点）。来源：公司官网OTC-HOPE是一项针对OTC缺乏症男性新生儿患者的首次人体临床试验（I/II期，招募7个月以下被确诊为严重新生儿OTC缺乏症的男婴），此前已在英国和澳大利亚获批开展临床。该研究的主要终点是评估单剂量静脉给药后ECUR-506的安全性和耐受性。次要终点是评估ECUR-506的药代动力学和疗效。此外，研究的探索性终点将评估疾病特异性生物标志物、发育里程碑和生活质量。据称，ECUR-506是首个在美国被批准用于婴儿研究的体内基因插入项目，也代表了ARCUS®核酸酶第一次在临床中被用于插入功能基因。来源：公司官网“对于许多孩子被诊断为新生儿OTC缺乏症的家庭来说，肝移植是唯一的治疗选择，但有严重风险，需要大量的免疫抑制治疗来防止移植排斥。ECUR-506代表了儿童在不需要移植的情况下长期产生功能性OTC酶的希望。”iECURE首席医学官Gabriel M. Cohn博士说道。参考资料：[1]https://iecure.com/news/iecure-announces-fda-clearance-of-investigational-new-drug-application-for-ecur-506-to-initiate-otc-hope-trial-for-treatment-of-neonatal-onset-ornithine-transcarbamylase-deficiency-in-the-u-s/[2]https://endpts.com/fda-greenlights-first-test-of-gene-editing-therapy-in-babies-from-jim-wilson-startup/医药魔方Pro新靶点 新技术 新疗法商务合作：13502093012媒体合作：15895423126Copyright © 2023 PHARMCUBE. All Rights Reserved.欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

Nearly 25 years ago, a young man with an inherited liver disease died from a vicious immune reaction to an experimental gene therapy. Now Jim Wilson, the scientist behind that failed treatment, is back with a new attempt to cure the disease, this time by editing the genes of newborns and infants. Philadelphia-based iEcure, one of several biotech companies spun out of Wilson’s expansive gene therapy program at the University of Pennsylvania, is preparing to treat babies up to 9 months of age with the severest form of the metabolic condition, called ornithine transcarbamylase deficiency. You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.

Clinical trial sites in the United States, United Kingdom, and Australia will evaluate ECUR-506, an investigational gene editing-based therapy, in newborn males with neonatal onset Ornithine Transcarbamylase (OTC) deficiency ECUR-506 is the first in vivo gene insertion program authorized for clinical investigation in infants in the U.S. PHILADELPHIA--(BUSINESS WIRE)-- iECURE, Inc., a gene editing company focused on the development of mutation-agnostic in vivo gene insertion, or knock-in, editing therapies for the treatment of liver disorders with significant unmet need, announced today clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) for ECUR-506 in Ornithine Transcarbamylase (OTC) deficiency. ECUR-506 will be evaluated in the OTC-HOPE study in newborn males with genetically confirmed neonatal onset OTC deficiency. The OTC-HOPE study was previously cleared to begin in the United Kingdom by the Medicines & Healthcare Products Regulatory Agency (MHRA) and Australia by the Therapeutic Goods Administration (TGA). “With this IND clearance, we are now activating sites in three countries in distinct geographical areas – United States, United Kingdom and Australia – which will facilitate families’ ability to access this landmark clinical trial,” said Joe Truitt, Chief Executive Officer of iECURE. “We are working diligently to open sites so we can start enrolling patients for dosing. The trial will be accepting eligible baby boys with neonatal onset OTC deficiency from all over the world, and we hope to see positive safety data and indications of efficacy with this trial.” The OTC-HOPE study is a Phase 1/2 first-in-human study in newborn males with genetically confirmed neonatal onset OTC deficiency. It is designed primarily to assess the safety and tolerability of ECUR-506 following intravenous administration of a single dose. Secondary objectives are to assess the pharmacokinetics and efficacy of ECUR-506. In addition, exploratory endpoints will assess disease-specific biologic markers, developmental milestones and quality of life. The ECUR-506 program is the first in vivo gene insertion program to be cleared in the U.S. for study in infants, and it represents the first time that the ARCUS® nuclease has been used to provide an in vivo insertion point for a functional gene in the clinic. “There is a significant need for clinical research and treatment options for newborns with severe, neonatal onset OTC deficiency,” said Gabriel M. Cohn, MD, Chief Medical Officer of iECURE. “For many families whose children are diagnosed with neonatal onset OTC deficiency, liver transplant is the only curative option, but carries with it serious risks and requires considerable immunosuppressant therapy to prevent transplant rejection. ECUR-506 represents hope for potentially enabling children to produce functional OTC enzyme in the long term without the need for transplantation.” “This milestone is the culmination of over 8 years of pre-clinical research in my laboratory addressing gene editing strategies for severe rare liver metabolic diseases,” said James M. Wilson, M.D., Ph.D., Rose H. Weiss professor and director, Orphan Disease Center; professor in the Departments of Medicine and Pediatrics, Perelman School of Medicine; and director of the Gene Therapy Program (GTP) at the University of Pennsylvania, whose laboratory developed ECUR-506 as a novel gene editing approach to treat OTC deficiency. “We hope that treatment with this investigational therapeutic will show promise for clinically meaningful improvements for infants with neonatal onset OTC deficiency and their families.” About ECUR-506 iECURE’s approach to gene editing for its initial programs, including OTC deficiency, relies on the delivery of two adeno-associated virus (AAV) capsids, each carrying different payloads. ECUR-506 comprises two vectors, an ARCUS® nuclease vector targeting gene editing in the well-characterized PCSK9 gene locus and a donor vector that inserts the desired functional OTC gene. iECURE has licensed the ARCUS nuclease for ECUR-506 from Precision BioSciences.1 The cut in the PCSK9 site serves as the insertion site for the OTC gene, providing a potential path to permanent expression of a healthy gene. ECUR-506 is being studied in the OTC-HOPE study, the first clinical meganuclease-based in vivo gene insertion program. About the OTC-HOPE Study The OTC-HOPE study is a Phase 1/2 first-in-human clinical trial of ECUR-506 in baby boys with genetically confirmed neonatal onset OTC deficiency and will test differing dose levels of ECUR-506. The study is enrolling baby boys up to seven months who are diagnosed with severe neonatal onset OTC deficiency and meet certain other criteria. The primary objective is to assess the safety and tolerability of intravenous administration of a single dose of ECUR-506. It will also assess the pharmacokinetics and efficacy of ECUR-506 administration and the potential effects of ECUR-506 on disease-specific biologic markers, developmental milestones and quality of life. About iECURE iECURE is a clinical-stage 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. We believe our 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. Our management team has extensive experience in executing global orphan drug and gene therapy clinical trials and successfully commercializing multiple products. We intend to leverage our team’s core strength in research and development strategy to identify what we believe to be the most suitable target and modality for our product candidates to address particular liver diseases. We are 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 preclinical and translational expertise and infrastructure, which has helped generate our initial pipeline of potential product candidates. For more information, visit and follow on LinkedIn. About Precision BioSciences & ARCUS® Precision BioSciences, Inc. is an advanced gene editing company dedicated to improving life (Nasdaq: DTIL) with its novel and proprietary ARCUS® genome editing platform that is designed to differ 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, Precision’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, visit . Penn’s Financial Disclosure The University of Pennsylvania (Penn) and Dr. Wilson each hold equity interests in iECURE. Penn also receives significant sponsored research support from iECURE, and both Penn and Dr. Wilson stand to benefit from licensing revenues received from iECURE based on successful technology development and commercialization of the technologies licensed from Penn. Dr. Wilson serves as Chief Scientific Advisor for iECURE. [1] iECURE has licensed the ARCUS® nuclease from Precision BioSciences for four gene insertion programs including OTC, CTLN1 and PKU.