NEW YORK--(BUSINESS WIRE)--Neurogene Inc., a clinical-stage company founded to bring life-changing genetic medicines to patients and families affected by rare neurological diseases, announced today the dosing of the first two female pediatric patients with Rett syndrome in its ongoing Phase 1/2 trial of NGN-401.

纽约-（商业线）-Neurogene Inc.是一家临床阶段公司，成立旨在为受罕见神经系统疾病影响的患者和家属带来改变生活的遗传药物，今天宣布前两名女性儿科Rett综合征患者在其正在进行的NGN-401 1/2期试验中。

Rett syndrome is a debilitating, X-linked, neurodevelopmental disorder with significant unmet medical need. To date, NGN-401 has been well-tolerated with no treatment-emergent or procedure-related SAEs, and no signs of transgene-related overexpression toxicity..

Rett综合征是一种使人衰弱的X连锁神经发育障碍，其医疗需求尚未得到满足。迄今为止，NGN-401耐受性良好，没有治疗出现或程序相关的SAE，也没有转基因相关过表达毒性的迹象。。

NGN-401 is an investigational adeno-associated virus (AAV) gene therapy candidate for Rett syndrome purposefully designed and administered to maximize the therapeutic activity while averting transgene overexpression toxicities. NGN-401 delivers the full-length human methyl cytosine binding protein 2 (MECP2) gene, providing an optimal gene replacement approach.

NGN-401是Rett综合征的研究性腺相关病毒（AAV）基因治疗候选物，旨在设计和施用以最大化治疗活性，同时避免转基因过表达毒性。NGN-401提供全长人甲基胞嘧啶结合蛋白2（MECP2）基因，提供最佳的基因替换方法。

Moreover, NGN-401 leverages Neurogene’s novel and proprietary Expression Attenuation via Construct Tuning (EXACT) gene regulation technology, which provides highly controlled and consistent MeCP2 expression on a cell-by-cell basis, thus avoiding the overexpression related toxicities associated with conventional gene therapy.

此外，NGN-401通过构建调整（精确）基因调控技术利用Neurogene新颖和专有的表达衰减，该技术在逐个细胞的基础上提供高度可控和一致的MeCP2表达，从而避免与常规基因治疗相关的过度表达相关毒性。

In non-clinical studies with NGN-401 at clinically relevant doses, cardinal features of Rett syndrome were ameliorated, and no overexpression toxicity was observed. These data were part of the robust non-clinical package that supported the U.S. Food and Drug Administration’s (FDA) decision to allow Neurogene to proceed directly into a pediatric population for its first-in-human study.

在临床相关剂量的NGN-401的非临床研究中，Rett综合征的主要特征得到改善，并且未观察到过表达毒性。这些数据是支持美国食品药品监督管理局（FDA）决定允许Neurogene直接进入儿科人群进行首次人体研究的强大非临床软件包的一部分。

NGN-401 has also been granted Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation by the FDA..

NGN-401也被FDA授予孤儿药名称，罕见儿科疾病名称和快速通道名称。。

“While gene therapy has proven to be a powerful tool in the treatment armamentarium for a number of devastating genetic conditions, the highly variable transgene expression associated with conventional gene therapies has limited its application in many complex neurological disorders, especially in Rett syndrome, in which MECP2 transgene overexpression is toxic,” said Bernhard Suter, M.D., Principal Investigator of the Phase 1/2 clinical trial, and Associate Professor of Pediatrics and Neurology at Baylor College of Medicine and Texas Children’s Hospital.

“虽然基因疗法已被证明是治疗各种毁灭性遗传疾病的有力工具，但与传统基因疗法相关的高度可变的转基因表达限制了它在许多复杂的神经系统疾病中的应用，特别是在瑞特综合征中，MECP2转基因过度表达是有毒的，”Bernhard Suter博士说。，1/2期临床试验的首席研究员，贝勒医学院和德克萨斯儿童医院的儿科和神经病学副教授。

“NGN-401 has been well tolerated to date in the first two patients dosed, consistent with the wide safety margins established in non-clinical studies conducted in disease models and in normal non-human primates.”.

“迄今为止，前两名患者对NGN-401的耐受性良好，这与在疾病模型和正常非人灵长类动物中进行的非临床研究中建立的广泛安全范围一致。”。

Ongoing Phase 1/2 Trial Update

正在进行的1/2期试验更新

The first-in-human, open-label, single-arm, multi-center Phase 1/2 clinical trial (NCT05898620) is evaluating NGN-401 at a dose of 1x1015 total vector genomes to assess the safety and tolerability of NGN-401 in female pediatric patients ages 4-10 with Rett syndrome. NGN-401 is administered as a one-time treatment using intracerebroventricular (ICV) administration, which has been shown to maximize the delivery of the therapeutic MECP2 gene to key areas of the brain underlying Rett syndrome pathobiology.

首次人体开放标签单臂多中心1/2期临床试验（NCT05898620）正在评估剂量为1x1015总载体基因组的NGN-401，以评估NGN-401在女性中的安全性和耐受性4-10岁患有Rett综合征的儿科患者。NGN-401作为一次性治疗使用脑室内（ICV）给药，已被证明可最大程度地将治疗性MECP2基因递送至Rett综合征病理生物学基础的大脑关键区域。

Clinical-grade NGN-401 for this trial was manufactured at Neurogene’s Good Manufacturing Practices (GMP) facility..

该试验的临床级NGN-401由Neurogene的良好生产规范（GMP）工厂生产。。

The first two patients were dosed sequentially in the third and fourth quarter of 2023 at Texas Children’s Hospital, an internationally recognized pediatric research center affiliated with Baylor College of Medicine, and the first clinical trial site to be opened in the U.S. for this study. Dr. Daniel Curry, M.D., director, Functional Neurosurgery and Epilepsy Surgery at Texas Children’s Hospital and professor, Neurosurgery and Surgery at Baylor College of Medicine, performed the procedure to administer the gene therapy..

前两名患者于2023年第三季度和第四季度在德克萨斯儿童医院（德克萨斯儿童医院）进行了顺序给药，德克萨斯儿童医院是贝勒医学院附属的国际公认的儿科研究中心，也是美国将要开展的第一个临床试验场所。德克萨斯儿童医院功能神经外科和癫痫外科主任，贝勒医学院神经外科和外科教授Daniel Curry博士执行了基因治疗的程序。。

NGN-401 has been well-tolerated to date, with no treatment-emergent or procedure-related SAEs, and no observations of transgene-related overexpression. Pending successful completion of the trial’s upcoming pre-planned independent Data and Safety Monitoring Board review, Neurogene expects to dose a third patient in the first quarter of 2024.

迄今为止，NGN-401的耐受性良好，没有治疗出现或程序相关的SAE，也没有观察到转基因相关的过表达。在成功完成试验即将进行的预先计划的独立数据和安全监测委员会审查之前，Neurogene预计将在2024年第一季度给第三名患者服用。

The first cohort is expected to enroll a total of five female pediatric patients, with a planned expansion pending additional data and subject to review by health authorities..

预计第一个队列将共招募五名女性儿科患者，计划扩大等待更多数据，并由卫生当局审查。。

“NGN-401 was purposefully designed to deliver a therapeutic benefit with the full length MECP2 gene, avoid toxicity associated with overexpression, and leverage the ICV route of delivery to maximize the biodistribution of the transgene to key areas of the brain underlying Rett syndrome. Based on published peer-reviewed non-clinical research, we know that Rett syndrome is caused by loss of function of MECP2 in the brain and spinal cord, and therefore we believe delivering robust transgene expression in these areas is essential for enabling a clinically meaningful benefit,” said Rachel McMinn, Ph.D., Founder and Chief Executive Officer of Neurogene.

“NGN-401旨在利用全长MECP2基因提供治疗益处，避免与过表达相关的毒性，并利用ICV递送途径最大化转基因向Rett综合征基础大脑关键区域的生物分布。基于已发表的同行评审的非临床研究，我们知道Rett综合征是由功能丧失引起的MECP2离子在大脑和脊髓中的表达，因此我们认为在这些区域提供强大的转基因表达对于实现临床上有意义的益处至关重要，”Neurogene的创始人兼首席执行官Rachel McMinn博士说。

“We are encouraged by the tolerability profile observed in our first two pediatric patients, and look forward to collecting sufficient follow up data on a larger number of patients to inform the therapeutic potential of NGN-401, which we believe could serve as a best-in-class therapy. We remain on track to report preliminary clinical data from the first cohort of patients in this trial in the fourth quarter of 2024, with additional data from an expanded number of patients expected in the second half of 2025.”.

“我们对前两名儿科患者的耐受性概况感到鼓舞，并期待收集大量患者的足够随访数据，以告知NGN-401的治疗潜力，我们认为这可以作为最佳的治疗方法。我们仍在跟踪中报告f中该试验中第一批患者的初步临床数据2024年第四季度，预计2025年下半年将有更多患者获得更多数据。”。

Dr. McMinn added, “On behalf of the entire Neurogene team, we extend our gratitude to all those making this study possible, with special appreciation for the patients and their families. Your resilience, courage, and support not only contribute to the progress of this research, but also inspire hope within the entire Rett syndrome community.

McMinn博士补充说：“我们代表整个Neurogene团队，特别感谢所有使这项研究成为可能的人，并特别感谢患者及其家属。您的适应能力，勇气和支持不仅有助于进展这项研究，而且激发了整个Rett综合征社区的希望。

Together, we have the potential to make a meaningful impact on improving the many lives affected by this devastating disease.”.

总之，我们有可能对改善受这种毁灭性疾病影响的许多生活产生有意义的影响。”。

About EXACT

确切地说

Neurogene’s novel and proprietary EXACT gene regulation platform technology is a self-contained transgene regulation platform that can be tuned to deliver a desired level of transgene expression within a narrow and therapeutically relevant range, with the goal of avoiding transgene-related toxicities associated with conventional gene therapy.

Neurogene新颖专有的精确基因调控平台技术是一个独立的转基因调控平台，可以在狭窄的治疗相关范围内调整以提供所需水平的转基因表达，目的是避免与传统基因相关的转基因相关毒性治疗。

EXACT is compatible with viral and non-viral delivery platforms..

EXACT与病毒和非病毒传输平台兼容。。

About NGN-401

关于NGN-401

NGN-401 is an investigational AAV9 gene therapy being developed as a one-time treatment for Rett syndrome. It is the first clinical candidate to deliver the full-length human MECP2 gene under the control of Neurogene’s EXACT technology. The EXACT technology utilized in NGN-401 is an important advancement in gene therapy for Rett syndrome, specifically because the disorder requires a treatment approach that enables targeted levels of MECP2 transgene expression without causing overexpression-related toxic effects associated with conventional gene therapy.

NGN-401是一种研究性AAV9基因疗法，正在开发作为Rett综合征的一次性治疗。它是第一个在Neurogene精确技术控制下递送全长人MECP2基因的临床候选药物。NGN-401中使用的确切技术是Rett综合征基因治疗的重要进展，特别是因为该疾病需要一种治疗方法，该方法能够靶向MECP2转基因表达水平，而不会引起与常规基因治疗相关的过表达相关毒性作用。

The robust non-clinical data package for NGN-401 provides evidence of a potentially compelling efficacy and safety profile in Rett syndrome..

针对NGN-401的强大的非临床数据包提供了在Rett综合征中潜在引人注目的疗效和安全性的证据。。

About Rett Syndrome

关于瑞特综合症

Rett syndrome is a rare genetic disorder that occurs almost exclusively in females, and leads to severe impairments that affect nearly every aspect of their lives. This includes their ability to speak, walk, eat, and breathe. The impact on patients and families is profound. Most females are nonverbal, lack motor skills, and require 24-hour care for all activities of daily living.

Rett综合征是一种罕见的遗传性疾病，几乎只发生在女性身上，并导致严重的损伤，几乎影响他们生活的各个方面。这包括他们说话，行走，进食和呼吸的能力。对患者和家庭的影响是深远的。大多数女性是非语言的，缺乏运动技能，需要24小时照顾所有日常生活活动。

Many females with Rett syndrome appear to understand the world around them, leaving many caregivers feeling that their daughters are intellectually and emotionally intact..

许多患有瑞特综合症的女性似乎了解他们周围的世界，许多看护人觉得他们的女儿在智力和情感上都完好无损。。

Rett syndrome is an X-linked, progressive, neurodevelopmental disorder. It has an estimated worldwide incidence of 1 out of every 10,000-15,000 live female births.

Rett综合征是X连锁，进行性神经发育障碍。据估计，全世界每10000-15000名活产女婴中就有1名发病。

The incidence in males is currently unknown. Advances in genetic testing and phenotypic identification have revealed that MECP2 mutations in males are responsible for a wide spectrum of neurological disorders, including Rett syndrome.

男性的发病率目前未知。基因测试和表型鉴定的进展表明，男性中的MECP2突变是导致包括Rett综合征在内的多种神经系统疾病的原因。

Rett syndrome is caused by mutations in the MECP2 gene that lead to deficiency of the methyl cytosine binding protein 2, an important protein responsible for normal function in the brain and other parts of the nervous system.

Rett综合征是由MECP2基因突变引起的，该突变导致甲基胞嘧啶结合蛋白2缺乏，甲基胞嘧啶结合蛋白2是负责大脑和神经系统其他部位正常功能的重要蛋白。

Females with Rett syndrome typically have normal development until 6-18 months of age, followed by a progressive deterioration of acquired skills such as gross and fine motor skills, purposeful hand function and communication. They subsequently develop stereotypic hand movements such as hand-wringing..

患有Rett综合征的女性通常会在6-18个月大之前发育正常，随后获得的技能逐渐恶化，例如粗略和精细的运动技能，有目的的手功能和沟通。随后，他们发展出定型的手部动作，例如拧手。。

Over time females may develop muscle contractures, rigidity, and debilitating scoliosis, along with periods of recurrent seizures, and burdensome gastrointestinal and breathing abnormalities.

随着时间的流逝，女性可能会出现肌肉挛缩，僵硬和使人衰弱的脊柱侧弯，以及反复发作的时期以及繁重的胃肠道和呼吸异常。

Although there are treatments available for Rett syndrome, there is no treatment option that addresses the root cause of disease and a significant unmet need still exists for new treatment options.

尽管有可用于Rett综合征的治疗方法，但尚无解决疾病根本原因的治疗方法，对于新的治疗方法仍存在重大的未满足需求。

About Neurogene

关于神经基因

The mission of Neurogene is to treat devastating neurological diseases to improve the lives of patients and families impacted by these rare diseases. Neurogene is developing novel approaches and treatments to address the limitations of conventional gene therapy in central nervous system disorders. This includes selecting a delivery approach to maximize distribution to target tissues and designing products to maximize potency and purity for an optimized efficacy and safety profile.

Neurogene的使命是治疗毁灭性的神经系统疾病，以改善受这些罕见疾病影响的患者和家庭的生活。Neurogene正在开发新的方法和治疗方法，以解决常规基因治疗在中枢神经系统疾病中的局限性。这包括选择递送方法以最大化向目标组织的分布并设计产品以最大化效力和纯度以获得优化的功效和安全性。

The Company’s novel and proprietary EXACT gene regulation platform technology allows for the delivery of therapeutic levels while limiting transgene toxicity associated with conventional gene therapy. Neurogene has constructed a state-of-the-art gene therapy manufacturing facility in Houston, Texas.

该公司新颖专有的精确基因调控平台技术允许提供治疗水平，同时限制与常规基因治疗相关的转基因毒性。Neurogene已在德克萨斯州休斯顿构建了最先进的基因治疗制造工厂。

GMP production of NGN-401 was conducted in this facility and will support pivotal clinical development activities. For more information, visit www.neurogene.com..

NGN-401的GMP生产在该设施中进行，并将支持关键的临床开发活动。欲了解更多信息，请访问www.neurogene.com。。

Cautionary Note Regarding Forward-Looking Statements

关于前瞻性陈述的警示

This communication contains forward-looking statements (including within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended (Securities Act). These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current expectations and beliefs of the management of Neurogene, as well as assumptions made by, and information currently available to, management of Neurogene.

本通讯包含前瞻性陈述（包括1934年“证券交易法”第21E条（经修订）和1933年“证券法”（经修订）（证券法）第27A条的含义。这些陈述可以基于当前对Neurogene管理的期望和信念，以及所做的假设和目前的信息，讨论关于未来计划，趋势，事件，运营结果或财务状况的目标，意图和期望。可用于管理Neurogene。

Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” and other similar expressions or the negative or plural of these words, or other similar expressions that are predictions or indicate future events or prospects, although not all forward-looking statements contain these words.

前瞻性陈述通常包括具有预测性并取决于或指代未来事件或条件的陈述，并包括诸如“可以”，“将会”，“应该”，“将会”，“期望”，“预期”，“计划”，“可能”，“相信”，“估计”，“项目”，“意图”和其他类似的表达方式，或这些词语的否定或复数，或其他类似的表达方式，这些表达方式是预测或指示未来的事件或前景，尽管并非所有前瞻性陈述都包含这些词语。

Statements that are not historical facts are forward-looking statements. Forward-looking statements in this communication include, but are not limited to, statements regarding the expected enrollment of and timing of data from Neurogene’s Phase 1/2 clinical trial; statements regarding the potential of, and expectations regarding, Neurogene’s programs, including NGN-101, NGN-401 and its research stage opportunities; the expected dosing of additional patients in Neurogene’s Phase 1/2 clinical trial; statements by Neurogene’s Founder and Chief Executive Officer.

不是历史事实的陈述是前瞻性陈述。本通讯中的前瞻性陈述包括但不限于有关Neurogene 1/2期临床试验数据的预期登记和时间安排的陈述；关于Neurogene计划（包括NGN-101，NGN-401及其研究阶段机会）的潜力和期望的声明；Neurogene 1/2期临床试验中其他患者的预期剂量；Neurogene的创始人兼首席执行官的声明。

Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performanc.

前瞻性陈述基于当前的信念和假设，这些信念和假设受到风险和不确定性的影响，不能保证未来的绩效。

This communication contains hyperlinks to information that is not deemed to be incorporated by reference into this communication.

本通信包含指向不被视为通过引用并入本通信的信息的超链接。

Important Additional Information About the Proposed Transactions Has Been Filed with the SEC

有关拟议交易的重要附加信息已提交给SEC

This communication is not a substitute for the registration statement or for any other document that Neoleukin has filed with the SEC in connection with the proposed transactions. In connection with the proposed transactions, Neoleukin has filed a registration statement on Form S-4 that contains a proxy statement/prospectus of Neoleukin.

本通信不能替代注册声明或Neoleukin向SEC提交的与拟议交易有关的任何其他文件。关于拟议的交易，Neoleukin已就表格S-4提交了一份注册声明，其中包含Neoleukin的代理声明/IPO。

NEOLEUKIN URGES INVESTORS AND STOCKHOLDERS TO READ THE REGISTRATION STATEMENT, PROXY STATEMENT/PROSPECTUS AND ANY OTHER RELEVANT DOCUMENTS THAT MAY BE FILED WITH THE SEC, AS WELL AS ANY AMENDMENTS OR SUPPLEMENTS TO THESE DOCUMENTS, CAREFULLY AND IN THEIR ENTIRETY BECAUSE THEY CONTAIN IMPORTANT INFORMATION ABOUT NEOLEUKIN, NEUROGENE, THE PROPOSED TRANSACTIONS AND RELATED MATTERS.

NEOLEUKIN敦促投资者和股东仔细和完整地阅读注册声明，代理声明/IPO和可能向SEC提交的任何其他相关文件，以及对这些文件的任何修改或补充，因为它们包含重要信息关于NEOLEUKIN，NEUROGENE，拟议交易和相关事项。

Investors and stockholders can obtain free copies of the proxy statement/prospectus and other documents filed by Neoleukin with the SEC through the website maintained by the SEC at www.sec.gov. In addition, investors and stockholders should note that Neoleukin communicates with investors and the public using its website (www.neoleukin.com), the investor relations website (https://investor.neoleukin.com/) where anyone can obtain free copies of the proxy statement/prospectus and other documents filed by Neoleukin with the SEC and stockholders are urged to read the proxy statement/prospectus and the other relevant materials before making any voting or investment decision with respect to the proposed transactions..

投资者和股东可以通过证券交易委员会在www.SEC.gov维护的网站获得Neoleukin向证券交易委员会提交的代理声明/IPO和其他文件的免费副本。此外，投资者和股东应注意，Neoleukin可以通过投资者关系网站www.Neoleukin.com与投资者和公众沟通(https://investor.neoleukin.com/)如果有人可以获得代理声明/IPO以及Neoleukin与证券交易委员会提交的其他文件的免费副本，并且敦促股东在就拟议交易做出任何投票或投资决定之前阅读代理声明/IPO和其他相关材料。。

Participants in the Solicitation

参与征集

Neoleukin, Neurogene and their respective directors and executive officers may be considered participants in the solicitation of proxies in connection with the proposed transaction. Information about Neoleukin’s directors and executive officers who may, under the rules of the SEC, be deemed participants in the solicitation of the stockholders of Neoleukin in connection with the proposed transaction, including a description of their direct or indirect interests, by security holdings or otherwise, is set forth in the proxy statement/prospectus included in the registration statement on Form S-4 initially filed by Neoleukin with the SEC on August 21, 2023, as subsequently amended on September 28, 2023, October 18, 2023 and November 8, 2023..

Neoleukin，Neurogene及其各自的董事和执行官可被视为与拟议交易有关的代理人征集的参与者。根据美国证券交易委员会的规定，有关Neoleukin董事和执行官的信息可能被视为与拟议交易有关的Neoleukin股东征集的参与者，包括对其直接或间接利益的描述，安全控股或其他，是由Neoleukin于2023年8月21日向SEC提交的S-4表格的注册声明中包含的代理声明/IPO中规定的，随后于2023年9月28日，2023年10月18日和11月8日进行了修订，2023年。。