First patient received dose level 2 of RGX-202, a potential one-time AAV Therapeutic for the treatment of Duchenne that includes an optimized transgene for a novel microdystrophin

第一个病人接受剂量水平2的RGX-202，一个潜在的一次性AAV治疗杜兴氏，其中包括一个优化的转基因为一个新的微抗肌营养不良蛋白

On track for pivotal dose determination and initiation of pivotal program in 2024

在2024年确定关键剂量和启动关键计划的轨道上

ROCKVILLE, Md., Nov. 29, 2023 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced that the first patient received RGX-202 at dose level 2 in the Phase I/II AFFINITY DUCHENNE® trial. RGX-202 is an investigational one-time AAV Therapeutic for Duchenne muscular dystrophy (Duchenne), using the NAV® AAV8 vector to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain as well as a muscle-specific promoter to support a targeted therapy for improved resistance to muscle damage associated with Duchenne..

ROCKVILLE，Md。，2023年11月29日/PRNewswire/-REGENXBIO Inc.（纳斯达克股票代码：RGNX）今天宣布第一名患者在I/II期AFFINITY DUCHENNE®试验中接受剂量水平2的RGX-202。RGX-202是Duchenne肌营养不良症（Duchenne）的一次性AAV研究治疗药物，使用NAV AAV8载体为新型微营养不良蛋白提供转基因，该微营养不良蛋白包括C末端（CT）结构域的功能元件以及肌肉特异性启动子，以支持靶向治疗，以提高对Duchenne相关肌肉损伤的抵抗力。。

'Progressing to dose level 2 is an important milestone in our updated strategic plans and for accelerating the development of RGX-202,' said Kenneth T. Mills, President and Chief Executive Officer of REGENXBIO. 'There is a large unmet need for new therapies for boys with Duchenne, and the market is capable of supporting multiple gene therapies.

REGENXBIO总裁兼首席执行官Kenneth T.Mills说：“进入剂量水平2是我们更新的战略计划和加速RGX-202发展的重要里程碑。”对于Duchenne男孩的新疗法有很大的未满足的需求，市场能够支持多种基因疗法。

We believe RGX-202 has unique, differentiating features that support its potential to be a best-in-class product.'.

我们相信RGX-202具有独特的，与众不同的功能，支持其成为一流产品的潜力。

Initial biomarker data in two patients who received RGX-202 at dose level 1 who completed three-month assessment demonstrated robust RGX-202 microdystrophin expression with localization to the muscle cell membrane. In recently completed preclinical efficacy studies, RGX-202 at dose level 2 showed improvement in functional performance, compared to dose level 1, as determined by forelimb muscle strength and treadmill exhaustion in mdx mice..

在完成三个月评估的剂量水平为1的两名接受RGX-202的患者中，最初的生物标志物数据显示了强大的RGX-202微肌营养不良蛋白表达，并定位于肌肉细胞膜。在最近完成的临床前疗效研究中，与剂量水平1相比，剂量水平2的RGX-202显示功能性能改善，如通过mdx小鼠的前肢肌肉力量和跑步机耗尽所确定的。。

REGENXBIO expects to share initial strength and functional assessment data for both dose levels and anticipates pivotal dose determination and the initiation of a pivotal program in 2024. The Company plans to use RGX-202 microdystrophin expression as a surrogate endpoint to support a Biologics License Application (BLA) filing using the accelerated approval pathway..

REGENXBIO预计将分享两种剂量水平的初始强度和功能评估数据，并预计2024年关键剂量的确定和关键计划的启动。该公司计划使用RGX-202微肌营养不良蛋白表达作为替代终点，以支持使用加速批准途径提交生物制剂许可申请（BLA）。。

AFFINITY DUCHENNE Trial DesignThe Phase I/II AFFINITY DUCHENNE trial is a multicenter, open-label dose escalation and dose expansion clinical study to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous (IV) dose of RGX-202 in patients with Duchenne. In the dose evaluation phase of the trial, four ambulatory, pediatric patients (ages 4 to 11 years old) are expected to enroll in two cohorts with doses of 1x1014 (GC)/kg body weight (n=2) and 2x1014 GC/kg body weight (n=2).

亲和DUCHENNE试验设计I/II期亲和DUCHENNE试验是一项多中心，开放标签剂量递增和剂量扩展临床研究，用于评估一次性静脉注射（IV）剂量RGX-202的安全性，耐受性和临床疗效在DUCHENNE患者中。在试验的剂量评估阶段，预计四名门诊儿科患者（年龄4至11岁）将参加两个队列，剂量为1x1014（GC）/kg体重（n=2）和2x1014 GC/kg体重（n=2）。

After an independent safety data review for each cohort, a dose expansion phase of the trial may allow for additional patients to be enrolled..

在对每个队列进行独立的安全性数据审查后，试验的剂量扩展阶段可能允许其他患者入组。。

The trial design was informed by the Duchenne community and engagement with key opinion leaders, including a comprehensive, short-term, prophylactic immunosuppression regimen to proactively mitigate potential complement-mediated immunologic responses, and inclusion criteria based on dystrophin gene mutation status, including DMD gene mutations in exons 18 and above.

试验设计由Duchenne社区提供信息，并与主要意见领袖进行接触，包括全面，短期，预防性免疫抑制方案，以主动减轻潜在的补体介导的免疫反应，以及基于肌营养不良蛋白基因突变状态的纳入标准，包括DMD基因外显子18及以上的突变。

Trial endpoints include safety, immunogenicity assessments, pharmacodynamic and pharmacokinetic measures of RGX-202, including microdystrophin protein levels in muscle, and strength and functional assessments, including the North Star Ambulatory Assessment (NSAA) and timed function tests..

试验终点包括RGX-202的安全性，免疫原性评估，药效学和药代动力学测量，包括肌肉中的微肌营养不良蛋白水平，以及力量和功能评估，包括北极动态评估（NSAA）和定时功能测试。。

About RGX-202RGX-202 is designed to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain found in naturally occurring dystrophin. Presence of the CT domain has been shown in preclinical studies to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice.

关于RGX-202RGX-202的设计旨在为新型微肌营养不良蛋白提供转基因，该微肌营养不良蛋白包括在天然存在的肌营养不良蛋白中发现的C端（CT）域的功能元件。临床前研究表明，CT结构域的存在可将几种关键蛋白募集到肌细胞膜上，从而改善肌肉对营养不良小鼠收缩诱导的肌肉损伤的抵抗力。

Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase translational efficiency and reduce immunogenicity. RGX-202 is designed to support the delivery and targeted expression of genes throughout skeletal and heart muscle using the NAV AAV8 vector, a vector used in numerous clinical trials, and a well-characterized muscle-specific promoter (Spc5-12)..

其他设计特征，包括密码子优化和CpG含量的降低，可能潜在地改善基因表达，提高翻译效率并降低免疫原性。RGX-202设计用于支持使用NAV AAV8载体，用于许多临床试验的载体和充分表征的肌肉特异性启动子（Spc5-12）在整个骨骼肌和心肌中递送和靶向表达基因。。

About Duchenne Muscular DystrophyDuchenne is a severe, progressive, degenerative muscle disease, affecting 1 in 3,500 to 5,000 boys born each year worldwide. Duchenne is caused by mutations in the Duchenne gene which encodes for dystrophin, a protein involved in muscle cell structure and signaling pathways.

关于杜兴氏肌营养不良症（Duchenne Muscular DystrophyDuchenne）是一种严重的进行性退行性肌肉疾病，每年影响全世界3500至5000名男孩中的1名。Duchenne是由Duchenne基因突变引起的，该基因编码肌营养不良蛋白，肌营养不良蛋白是一种参与肌肉细胞结构和信号通路的蛋白质。

Without dystrophin, muscles throughout the body degenerate and become weak, eventually leading to loss of movement and independence, required support for breathing, cardiomyopathy and premature death..

如果没有肌营养不良蛋白，整个身体的肌肉就会退化并变得虚弱，最终导致运动和独立性丧失，需要呼吸，心肌病和过早死亡的支持。。

About REGENXBIO Inc.REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. REGENXBIO's NAV Technology Platform, a proprietary adeno-associated virus (AAV) gene delivery platform, consists of exclusive rights to more than 100 novel AAV vectors, including AAV7, AAV8 and AAV9.

关于REGENXBIO Inc.REGENXBIO是一家领先的临床阶段生物技术公司，致力于通过基因治疗的治疗潜力改善生活。REGENXBIO的NAV Technology平台是一个专有的腺相关病毒（AAV）基因传递平台，拥有100多种新型AAV载体的专有权，包括AAV7，AAV8和AAV9。

REGENXBIO and its third-party NAV Technology Platform Licensees are applying the NAV Technology Platform in the development of a broad pipeline of candidates, including late-stage and commercial programs, in multiple therapeutic areas. REGENXBIO is committed to a '5x'25' strategy to progress five AAV Therapeutics from our internal pipeline and licensed programs into pivotal-stage or commercial products by 2025..

REGENXBIO及其第三方NAV技术平台许可证持有者正在将NAV技术平台应用于开发广泛的候选人渠道，包括后期和商业计划，涉及多个治疗领域。REGENXBIO致力于制定“5x”25“战略，到2025年将五种AAV治疗药物从我们的内部管道和许可计划推进到关键阶段或商业产品。。

FORWARD-LOOKING STATEMENTSThis press release includes 'forward-looking statements,' within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements express a belief, expectation or intention and are generally accompanied by words that convey projected future events or outcomes such as 'believe,' 'may,' 'will,' 'estimate,' 'continue,' 'anticipate,' 'assume,' 'design,' 'intend,' 'expect,' 'could,' 'plan,' 'potential,' 'predict,' 'seek,' 'should,' 'would' or by variations of such words or by similar expressions.

前瞻性声明本新闻稿包括1933年“证券法”第27A条（经修订）和1934年“证券交易所法”第21E条（经修订）含义内的“前瞻性声明”。这些陈述表达了一种信念，期望或意图，并且通常伴随着传达预测的未来事件或结果的词语，例如“相信”，“可能”，“将会”，“估计”，“继续”，“预期”，“假设，“设计”，“意图”，“期望”，“可能”，“计划”，“潜力”，“预测”，“寻求”，“应该”，或者通过这些词语的变化或类似的表达。

The forward-looking statements include statements relating to, among other things, REGENXBIO's future operations, clinical trials, costs and cash flow. REGENXBIO has based these forward-looking statements on its current expectations and assumptions and analyses made by REGENXBIO in light of its experience and its perception of historical trends, current conditions and expected future developments, as well as other factors REGENXBIO believes are appropriate under the circumstances.

前瞻性陈述包括与REGENXBIO未来运营，临床试验，成本和现金流量等有关的陈述。REGENXBIO根据REGENXBIO的经验和对历史趋势，现状和预期未来发展的看法，以及REGENXBIO认为合适的其他因素，对其当前的期望和假设以及REGENXBIO所做的分析作出了前瞻性陈述。情况。

However, whether actual results and developments will conform with REGENXBIO's expectations and predictions is subject to a number of risks and uncertainties, including the timing of enrollment, commencement and completion and the success of clinical trials conducted by REGENXBIO, its licensees and its partners, the timing of commencement and completion and the success of preclinical studies conducted by REGENXBIO and its development partners, the timely development and launch of new products, the ability to obtain and maintain regulatory approval of product candidates, the ability to obtain and maintain intellectual property protection for product candidates and technology, trends and challe.

但是，实际结果和发展是否符合REGENXBIO的期望和预测，取决于许多风险和不确定性，包括注册时间，开始和完成以及REGENXBIO，其许可证持有者及其合作伙伴进行的临床试验的成功，REGENXBIO及其开发合作伙伴开展和完成临床前研究的时间，新产品的及时开发和推出，获得和维持产品候选人监管批准的能力，获得和维护知识产权保护的能力为产品候选人和技术，趋势和查尔。

Contacts:

联络：

Dana CormackCorporate Communications[email protected]

Dana-CormackCorporate Communications[电子邮件保护]

Investors:Chris BrinzeyICR Westwicke339-970-2843[email protected]

投资者：Chris BrinzeyCR Westwick339-970-2843〔email protected〕

SOURCE REGENXBIO Inc.

来源REGENXBIO股份有限公司。