RGX-202, a potential one-time AAV Therapeutic for the treatment of Duchenne that includes an optimized transgene for a novel microdystrophin, continues to be well-tolerated in three patients from dose level 1 (1x1014 GC/kg)

RGX-202是一种潜在的一次性AAV治疗Duchenne的药物，包括一种新型微抗肌营养不良蛋白的优化转基因，在剂量水平1（1x1014 GC/kg）的3名患者中继续耐受良好

Initial biomarker data in two patients who completed three-month assessment demonstrate robust microdystrophin expression with localization to the muscle cell membrane

两名完成三个月评估的患者的初步生物标志物数据显示，肌营养不良蛋白表达强烈，定位于肌细胞膜

Patient aged 4.4 years old had expression level at 38.8% of control

4.4岁患者表达水平为对照组的38.8%

Trial dose escalation expected by end of 2023

预计到2023年底试用剂量增加

Pivotal dose determination and initiation of pivotal program anticipated in 2024

预计2024年关键剂量的确定和关键方案的启动

Plan to use RGX-202 microdystrophin as a surrogate endpoint to support a Biologics License Application filing using the accelerated approval pathway

计划使用RGX-202微肌营养不良蛋白作为替代终点，以支持使用加速批准途径提交生物制剂许可申请

RGX-202 development program uses commercial-ready cGMP material from the REGENXBIO Manufacturing Innovation Center

RGX-202开发项目使用来自REGENXBIO制造创新中心的商用cGMP材料

Conference call today, Tuesday, October 3, 2023, at 4:30 p.m. ET

电话会议今天，星期二，2023年10月3日，下午4:30

ROCKVILLE, Md., Oct. 3, 2023 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced additional interim safety data and initial efficacy data from the Phase I/II AFFINITY DUCHENNE™ trial of RGX-202 for the treatment of Duchenne Muscular Dystrophy (Duchenne). Results were shared at the 28th Annual International Congress of the World Muscle Society..

ROCKVILLE，Md.，2023年10月3日/PRNewswire/-REGENXBIO Inc.（纳斯达克股票代码：RGNX）今天宣布了来自I/II期AFFINITY DUCHENNE的额外临时安全性数据和初始疗效数据™ RGX-202治疗杜氏肌营养不良症（Duchenne）的试验。结果在世界肌肉学会第28届年度国际大会上分享。。

'Duchenne is a rare degenerative disease, and without a functional dystrophin protein, muscles progressively weaken, leading to loss of mobility and declining respiratory and cardiac function,' said Olivier Danos, Ph.D., Chief Scientific Officer of REGENXBIO. 'The unique construct of RGX-202, inclusive of the C-Terminal domain, has the potential to make a meaningful impact for patients and we are encouraged by these interim safety and efficacy results.'.

REGENXBIO首席科学官Olivier Danos博士说：“Duchenne是一种罕见的退行性疾病，没有功能性肌营养不良蛋白，肌肉逐渐衰弱，导致活动能力丧失，呼吸和心脏功能下降。”RGX-202的独特构建体，包括C末端结构域，有可能对患者产生有意义的影响，我们对这些临时安全性和有效性结果感到鼓舞。

RGX-202 is an investigational one-time AAV therapeutic for 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..

RGX-202是Duchenne的一项研究性一次性AAV治疗药物，使用NAV®AAV8载体为新型微肌营养不良蛋白提供转基因，其中包括C末端（CT）结构域的功能元件以及肌肉特异性启动子。支持靶向治疗，以提高对Duchenne相关肌肉损伤的抵抗力。。

Data were presented from dose level 1 (1x1014 genome copies (GC)/kg body weight) of the ongoing Phase I/II AFFINITY DUCHENNE™ trial, which continues to recruit ambulatory patients (aged 4 to 11 years) and is using commercial-ready cGMP material from the REGENXBIO Manufacturing Innovation Center.

数据来自正在进行的I/II期亲和DUCHENNE的剂量水平1（1x1014基因组拷贝（GC）/kg体重）™ 该试验将继续招募非卧床患者（4至11岁），并使用REGENXBIO制造创新中心提供的商业就绪cGMP材料。

Safety UpdateAs of September 28, 2023, RGX-202 was reported to be well tolerated with no drug-related serious adverse events in three patients, aged 4.4, 10.6 and 6.3 years, dosed to date at dose level 1. Time of post-administration follow up ranges from three weeks to more than five months. The two patients who reached three-month follow-up have completed the immunosuppression regimen per study protocol..

安全性更新据报道，2023年9月28日，RGX-202耐受性良好，3名患者，年龄分别为4.4,10.6和6.3岁，无药物相关严重不良事件，剂量水平为1。给药后随访时间从三周到五个月以上不等。达到三个月随访的两名患者按照研究方案完成了免疫抑制方案。。

Biomarker DataInitial biomarker data from two patients who completed three-month trial assessments indicate encouraging increases in expression of RGX-202 microdystrophin from bicep muscle biopsies taken at three months following one-time administration of RGX-202. In addition, RGX-202 microdystrophin was detectable by immunofluorescence staining throughout muscle tissue at three months, with RGX-202 microdystrophin protein localized to the sarcolemma..

生物标志物数据来自完成三个月试验评估的两名患者的初始生物标志物数据表明，在一次性施用RGX-202后三个月取得的二头肌活组织检查中RGX-202微肌营养不良蛋白的表达令人鼓舞地增加。此外，在三个月的整个肌肉组织中，通过免疫荧光染色可检测到RGX-202微肌营养不良蛋白，其中RGX-202微肌营养不良蛋白定位于肌膜。。

RGX-202 microdystrophin levels were measured using an automated and precise western blot method (Jess), and comparable results were confirmed with a proprietary liquid chromatography-mass spectrometry (LC-MS) method.

使用自动且精确的蛋白质印迹法（Jess）测量RGX-202微肌营养不良蛋白水平，并通过专有的液相色谱-质谱（LC-MS）方法确认可比的结果。

In the patient aged 4.4 years old, RGX-202 microdystrophin expression was measured to be 38.8% compared to control. A reduction from baseline in serum creatinine kinase (CK) levels of 43% was observed at ten weeks, supporting evidence of clinical improvement. Elevated CK levels are associated with muscle injury and are uniformly elevated in patients with Duchenne..

在4.4岁的患者中，与对照组相比，RGX-202微肌营养不良蛋白的表达为38.8%。在十周时观察到血清肌酐激酶（CK）水平从基线降低了43%，支持了临床改善的证据。CK水平升高与肌肉损伤有关，在Duchenne患者中均匀升高。。

In the patient aged 10.6 years old, RGX-202 microdystrophin expression was measured to be 11.1% compared to control and a reduction from baseline in serum CK levels of 44% was observed at ten weeks.

在10.6岁的患者中，与对照组相比，RGX-202微肌营养不良蛋白的表达为11.1%，并且在十周时观察到血清CK水平比基线降低了44%。

'I am encouraged by these initial results demonstrating that RGX-202 appears to be well tolerated and leads to robust microdystrophin expression in muscle tissue, which are important early findings,' said Aravindhan Veerapandiyan, M.D., Pediatric Neuromuscular Neurologist, Arkansas Children's Hospital, and primary investigator in the trial.

Aravindhan Veerapandiyan，医学博士，小儿神经肌肉神经病学家，阿肯色州儿童医院和主要研究人员说：“我对这些初步结果感到鼓舞，这些结果表明RGX-202似乎具有良好的耐受性，并导致肌肉组织中强烈的微肌营养不良蛋白表达，这是重要的早期发现。”。

'I know that there is still unmet need for these boys for new treatment options that have the potential to impact the trajectory of the disease.'.

“我知道这些男孩仍然需要新的治疗方案，这些方案有可能影响疾病的发展轨迹。”。

Clinical Program UpdatesREGENXBIO expects to dose patients at dose level 2 (2x1014 genome copies (GC)/kg body weight) in the Phase I/II AFFINITY DUCHENNE trial by the end of 2023. In addition, the trial protocol has been amended to accelerate the development of RGX-202, updating the dose expansion phase of the trial to begin after two patients, from the previous three patients..

临床计划更新RegenxBio预计在2023年底之前在I/II期亲和DUCHENNE试验中以剂量水平2（2×1014基因组拷贝（GC）/kg体重）给患者服用。此外，对试验方案进行了修订，以加速RGX-202的开发，更新试验的剂量扩展阶段，从前三名患者的两名患者开始。。

Today, REGENXBIO also provided an update on a newly completed preclinical efficacy study evaluating RGX-202 manufactured using REGENXBIO's NAVXpress™ commercial-ready process at both dose levels. 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.

今天，REGENXBIO还提供了一项新完成的临床前疗效研究的更新，该研究评估了使用REGENXBIO的NAVXpress制造的RGX-202™ 两种剂量水平的商业就绪工艺。与剂量水平1相比，剂量水平2的RGX-202显示功能性能的改善，如通过mdx小鼠中的前肢肌肉力量和跑步机耗尽所确定的。

This data further supports plans to immediately initiate dose escalation to dose level 2..

该数据进一步支持立即启动剂量递增至剂量水平2的计划。。

The Company expects to share initial strength and functional assessment data for both dose levels in 2024. Additionally, REGENXBIO expects to make a pivotal dose determination and initiate a pivotal program for RGX-202 in 2024.

该公司预计2024年将分享两种剂量水平的初始强度和功能评估数据。此外，REGENXBIO预计将在2024年确定关键剂量并启动RGX-202的关键计划。

'We are pleased to share these encouraging results and updates, enabling us to accelerate our development of RGX-202 with the goal of reaching pivotal phase faster,' said Kenneth T. Mills, President and Chief Executive Officer of REGENXBIO. 'We plan to scale up production of RGX-202 using commercial-ready cGMP material from the REGENXBIO Manufacturing Innovation Center to support a pivotal program in 2024, with a clear path to submit a BLA using the accelerated approval pathway, with RGX-202 microdystrophin as a surrogate endpoint for clinical benefit.

REGENXBIO总裁兼首席执行官Kenneth T.Mills说：“我们很高兴分享这些令人鼓舞的结果和更新，使我们能够加速RGX-202的开发，目标是更快地达到关键阶段。”我们计划使用来自REGENXBIO制造创新中心的商业就绪cGMP材料扩大RGX-202的生产，以支持2024年的关键计划，明确途径使用加速批准途径提交BLA，RGX-202微肌营养不良蛋白作为临床获益的替代终点。

This update firmly establishes RGX-202 as a key feature of our '5x'25' vision to have five gene therapies either on the market or in late-stage development by 2025.'.

这一更新坚定地将RGX-202确立为我们“5x'25”愿景的一个关键特征，即到2025年在市场上或在后期开发中拥有五种基因疗法。

Conference Call DetailsREGENXBIO will host a conference call Tuesday, October 3 at 4:30 p.m. ET with principal investigator, Dr. Aravindhan Veerapandiyan, to discuss these results and the RGX-202 program.

电话会议详情RegenXbio将于10月3日星期二下午4:30与首席研究员Aravindhan Veerapandiyan博士召开电话会议，讨论这些结果和RGX-202计划。

Listeners can register for the webcast via this link. Analysts wishing to participate in the question and answer session should use this link. A copy of the slides being presented will be available via the Company's investor website. Those who plan on participating are advised to join 15 minutes prior to the start time.

听众可以通过此链接注册网络广播。希望参加问答环节的分析师应该使用此链接。正在提交的幻灯片副本将通过公司的投资者网站提供。建议计划参加的人在开始前15分钟加入。

A replay of the webcast will also be available via the Company's investor website approximately two hours after the call's conclusion..

在通话结束后约两小时，公司的投资者网站也可以重播网络广播。。

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 genome copies (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基因组拷贝（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 up to seven additional patients to be enrolled at each dose level (for a total of up to nine patients in each dose cohort)..

在对每个队列进行独立的安全性数据审查之后，试验的剂量扩展阶段可以允许在每个剂量水平上招募多达7名额外的患者（每个剂量队列中总共多达9名患者）。。

The trial design consists of thorough safety measures 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.

试验设计包括由Duchenne社区提供的全面安全措施以及与主要意见领袖的接触，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，包括外显子18及以上的DMD基因突变。

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. Initial trial sites are located in the U.S., with additional sites in Canada and Europe expected to follow..

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。最初的试验地点位于美国，预计将在加拿大和欧洲增加其他地点。。

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, AAV9 and AAVrh10.

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平台是一种专有的腺相关病毒（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，AAV9和AAVrh10。

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:Dana CormackCorporate Communications[email protected]

联系人：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。