NEW YORK--(BUSINESS WIRE)--Neurogene Inc. (Nasdaq: NGNE), a clinical-stage company founded to bring life-changing genetic medicines to patients and families affected by rare neurological diseases, today announced positive interim clinical data in the first four participants in the low-dose cohort of its ongoing Phase 1/2 open-label trial designed to evaluate NGN-401 gene therapy for the treatment of female pediatric patients with Rett syndrome.

纽约--（商业新闻短讯）--Neurogene Inc.（纳斯达克：NGNE）是一家临床阶段公司，旨在为受罕见神经系统疾病影响的患者和家庭带来改变生命的遗传药物，今天宣布，在其正在进行的1/2期开放标签试验的低剂量队列中，前四名参与者的中期临床数据为阳性，该试验旨在评估NGN-401基因疗法治疗女性小儿Rett综合征患者。

Low-dose NGN-401 has demonstrated a favorable safety profile..

低剂量NGN-401具有良好的安全性。。

“Today marks an important day for Neurogene and the Rett syndrome community as we share positive interim data for NGN-401 from our low-dose cohort that shows the first four participants demonstrated meaningful gains of skills and developmental milestones in core clinical domains of Rett syndrome, which are not expected to occur when compared to and contextualized against the natural history of Rett syndrome.

“今天是Neurogene和Rett综合征社区的重要一天，因为我们分享了来自低剂量队列的NGN-401的积极中期数据，这些数据显示前四名参与者在Rett综合征的核心临床领域表现出有意义的技能和发展里程碑，与Rett综合征的自然史相比，预计不会发生这种情况。

Data were also concordant across multiple scales and show consistency of effect across patients, despite their unique clinical presentations at baseline,” said Rachel McMinn, Ph.D., Founder and Chief Executive Officer of Neurogene. “We are incredibly thankful to the participants, caregivers and Rett syndrome trial sites who are participating in our study.”.

Neurogene创始人兼首席执行官Rachel McMinn博士说：“尽管在基线时有独特的临床表现，但数据在多个尺度上也是一致的，并且显示出患者之间效果的一致性。”。“我们非常感谢参与我们研究的参与者，护理人员和Rett综合征试验地点。”。

“Rett syndrome is a devastating neurodevelopmental disease that is incredibly challenging for patients and their caregivers given there are no treatment options available to address the underlying cause of the disease,” said Aleksandra Jacobs, M.D., Ph.D., Professor of Pediatric Neurology, Albert Einstein College of Medicine and Director of the Center for Rett Syndrome in the Children’s Hospital at Montefiore Medical Center.

Aleksandra Jacobs医学博士、阿尔伯特·爱因斯坦医学院儿科神经病学教授、蒙特菲奥雷医学中心儿童医院Rett综合征中心主任说：“Rett综合征是一种毁灭性的神经发育疾病，对患者及其护理人员来说极具挑战性，因为目前尚无治疗方案来解决该疾病的根本原因。”。

“The totality of the outcomes shared today with NGN-401 gene therapy have never been seen before in the treatment of Rett syndrome. Notably, these initial participants acquired developmental skills post-treatment during the period in which the natural history of Rett syndrome indicates girls would not.

“今天与NGN-401基因治疗共享的全部结果在治疗Rett综合征方面从未见过。值得注意的是，这些最初的参与者在Rett综合征的自然史表明女孩不会的时期获得了治疗后的发展技能。

I look forward to the continued progress in this program and additional data to come.”.

我期待着这个项目的持续进展和更多的数据。”。

Interim Clinical Data as of Data Cut-Off Date of October 17, 2024

截至2024年10月17日数据截止日期的中期临床数据

Interim Safety Data (N=7)*

临时安全数据（N=7）*

Low-dose (1E15 vg) and high-dose (3E15 vg) NGN-401 have been well-tolerated with a favorable safety profile in the first seven pediatric participants (N=5 low-dose; N=2 high-dose):

低剂量（1E15 vg）和高剂量（3E15 vg）NGN-401在前七名儿科参与者中耐受性良好，安全性良好（N=5低剂量；N=2高剂量）：

No treatment-related serious adverse events (SAEs)

无治疗相关严重不良事件（SAE）

No signs or symptoms indicative of MeCP2 overexpression toxicity

没有迹象或症状表明MeCP2过度表达毒性

Most treatment-related adverse events (AEs) are known potential risks of adeno-associated virus (AAV), have been responsive to steroids, and are resolved or are resolving

大多数与治疗相关的不良事件（AE）是已知的腺相关病毒（AAV）的潜在风险，对类固醇有反应，并且已经解决或正在解决

No intracerebroventricular (ICV)-related AEs

无脑室内（ICV）相关AE

No seizures for any participants following NGN-401 treatment

NGN-401治疗后，任何参与者均无癫痫发作

*Today, Neurogene became aware of an emerging treatment-related SAE consistent with known risks of AAV gene therapy in the third high-dose participant who was recently dosed.

*今天，Neurogene意识到一种新出现的与治疗相关的SAE，这与最近服用的第三名高剂量参与者的AAV基因治疗的已知风险一致。

Low-Dose Interim Efficacy Data (N=4)

低剂量中期疗效数据（N=4）

The first four participants (age range 4-7 years old, efficacy assessments at 15, 12, 9, and 3 months post-dosing) in low-dose Cohort 1 showed consistent, concordant and durable improvements across key Rett syndrome assessments:

低剂量队列1中的前四名参与者（年龄范围4-7岁，给药后15、12、9和3个月的疗效评估）在关键的Rett综合征评估中显示出一致，一致和持久的改善：

All participants achieved a rating of “much improved,” or a score of 2, on the clinician-rated Clinical Global Impression Scale of Improvement (CGI-I) from baseline; a score of < 3 is considered clinically meaningful

所有参与者在临床医生评定的临床总体印象改善量表（CGI-I）上获得了“大大改善”的评分，即2分；3分被认为具有临床意义

All participants acquired skills and/or developmental milestones in one or more core clinical domains of Rett syndrome - hand function/fine motor, language/communication and ambulation/gross motor

所有参与者都在Rett综合征的一个或多个核心临床领域获得了技能和/或发展里程碑-手功能/精细运动，语言/交流和行走/粗大运动

These improvements include complex skills that are rarely learned in this population and skills that are rarely relearned after developmental regression when compared to the NIH-sponsored Rett syndrome natural history

这些改进包括在这个人群中很少学习到的复杂技能，以及与美国国立卫生研究院赞助的瑞特综合征自然史相比，在发育退化后很少重新学习的技能

New skills and milestones have increased and deepened over time

随着时间的推移，新技能和里程碑不断增加和加深

Initiation of Adolescent/Adult Cohort in NGN-401 Clinical Trial

NGN-401临床试验中青少年/成人队列的启动

Neurogene announced today that it has initiated an adolescent/adult Cohort 3 to gain initial data on the potential of NGN-401 to treat a broader patient population. This cohort is designed to enroll three participants ages 16 and above at the high dose.

Neurogene今天宣布，它已经启动了一个青少年/成人队列3，以获得有关NGN-401治疗更广泛患者群体潜力的初步数据。该队列旨在招募三名16岁及以上的高剂量参与者。

FDA Alignment on CMC Requirements to Initiate Future Registrational Trial and Support Potential Product Launch

FDA与CMC要求保持一致，以启动未来的注册试验并支持潜在的产品发布

Neurogene also announced today that it has gained alignment with the FDA on its potency assay strategy for NGN-401, which is necessary to have in place prior to initiating a registrational trial. In addition, the FDA is aligned with Neurogene’s manufacturing scale-up plans for NGN-401, which is important to support a future commercial product launch..

Neurogene今天还宣布，它已经与FDA就NGN-401的效力测定策略达成一致，这在开始注册试验之前是必要的。此外，FDA与Neurogene的NGN-401生产规模扩大计划保持一致，这对于支持未来的商业产品发布非常重要。。

Completed and Upcoming Milestones for the NGN-401 Program

NGN-401计划已完成和即将到来的里程碑

Plans to provide an update of registrational trial design in the first half of 2025

计划在2025年上半年更新注册试验设计

Plans to announce additional interim Phase 1/2 clinical data in the second half of 2025

计划在2025年下半年公布额外的中期1/2期临床数据

CLN5 Batten Disease Program Update

CLN5巴顿病计划更新

Neurogene announced today that the Company does not expect to move forward with the NGN-101 CLN5 Batten disease gene therapy program at this time. Given the rarity of the disease, continued investment in the program was predicated on alignment on a streamlined registrational pathway with FDA. To support a streamlined pathway, Neurogene submitted a Regenerative Medicine Advance Therapy (RMAT) application to the FDA.

Neurogene今天宣布，该公司目前预计不会推进NGN-101 CLN5巴顿病基因治疗计划。鉴于该疾病的罕见性，该计划的持续投资取决于与FDA的简化注册途径的一致性。为了支持简化的途径，Neurogene向FDA提交了再生医学高级治疗（RMAT）申请。

Despite the Company’s belief that the application met the standard of preliminary clinical evidence required to obtain an RMAT designation, the RMAT application was denied. Neurogene is currently evaluating options for the program..

尽管该公司认为该申请符合获得RMAT指定所需的初步临床证据标准，但RMAT申请被拒绝。Neurogene目前正在评估该计划的选择。。

Investor/Analyst Webcast Details

投资者/分析师网络广播详细信息

Management will host a live webcast and conference call today, November 11, 2024, at 4:30 p.m. ET to review the interim data from the NGN-401 clinical trial. Access information is available in the Investor Relations section of Neurogene’s website under Events, where the webcast replay will also be available for a limited time..

管理层将于今天，2024年11月11日，美国东部时间下午4:30主持一次网络直播和电话会议，以审查NGN-401临床试验的中期数据。访问信息可在Neurogene网站的“活动”下的“投资者关系”部分获得，网络广播重播也将在有限的时间内提供。。

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™ transgene regulation technology. EXACT technology 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..

。它是第一个在Neurogene的EXACT™转基因调控技术控制下传递全长人MECP2基因的临床候选者。精确技术是Rett综合征基因治疗的一项重要进展，特别是因为该疾病需要一种治疗方法，该方法可以实现MECP2转基因表达的靶向水平，而不会引起与常规基因治疗相关的过表达相关毒性作用。。

NGN-401 was selected by the U.S. Food and Drug Administration (FDA) for its START Pilot Program and has also received Regenerative Medicine Advance Therapy (RMAT) designation, orphan drug designation, Fast Track designation and rare pediatric designation from the FDA. Neurogene was previously granted an INTERACT meeting with the FDA regarding the EXACT technology.

NGN-401被美国食品和药物管理局（FDA）选择用于其START试点计划，并且还获得了FDA的再生医学高级治疗（RMAT）指定，孤儿药指定，快速通道指定和罕见儿科指定。。

NGN-401 also received orphan designation and advanced therapy medicinal product designation from the European Medicines Agency (EMA) and the Innovative Licensing and Application Pathway (ILAP) designation from the United Kingdom (UK) Medicines and Healthcare products Regulatory Agency (MHRA)..

NGN-401还获得了欧洲药品管理局（EMA）的孤儿指定和高级治疗药品指定，以及英国（英国）药品和保健品管理局（MHRA）的创新许可和应用途径（ILAP）指定。。

About Neurogene

关于Neurogene

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靶组织的分布，并设计产品以最大化效力和纯度以优化功效和安全性。

The Company’s novel and proprietary EXACT transgene 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.

该公司的新型专有精确转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。。

CGMP 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CGMP生产是在该设施中进行的，将支持关键的临床开发活动。有关更多信息，请访问www.neurogene.com。。