Del-brax FORTITUDE biomarker cohort designed for potential accelerated approval; plan to share regulatory update in Q2 2025

德尔布雷克斯FORTITUDE生物标志物队列设计用于潜在的加速批准；计划在2025年第二季度分享监管更新。

Regulatory alignment on global Phase 3 del-brax trial design and study initiation anticipated in Q2 2025

预计将在 2025 年第二季度就全球第三阶段 del-brax 试验设计和研究启动达成监管一致。

Plan to present topline data from FORTITUDE dose escalation cohorts in Q2 2025

计划在2025年第二季度公布FORTITUDE剂量递增队列的顶线数据。

On track to be first globally approved drug for FSHD

有望成为全球首个获批的FSHD药物

SAN DIEGO

圣地亚哥

,

，

March 31, 2025

2025年3月31日

/PRNewswire/ -- Avidity Biosciences, Inc. (Nasdaq:

/PRNewswire/ -- Avidity Biosciences, Inc.（纳斯达克：

RNA

RNA

), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs™), today announced the completion of enrollment in the biomarker cohort in the Phase 1/2 FORTITUDE™ clinical trial of delpacibart braxlosiran (del-brax) in people living with facioscapulohumeral muscular dystrophy (FSHD).

），一家致力于交付一类称为抗体寡核苷酸偶联物（AOCs™）的RNA治疗药物的生物制药公司，今天宣布在FORTITUDE™ 1/2期临床试验中，已完成对患有面肩肱型肌营养不良症（FSHD）的人群使用地尔帕西巴特-布拉克索利兰（del-brax）的生物标志物队列的入组。

A total of 51 participants were enrolled in the FORTITUDE biomarker cohort..

共有51名参与者入选了FORTITUDE生物标志物队列。

'Completing enrollment in the FORTITUDE biomarker cohort is an important milestone as we pursue a potential accelerated approval path in the U.S. for del-brax and work to bring the first approved drug to people living with this rare, devastating neuromuscular disease who have no treatment options as quickly as possible,' said .

“完成FORTITUDE生物标志物队列的入组是一个重要的里程碑，因为我们正在美国寻求del-brax的潜在加速审批路径，并努力尽快为这种罕见、严重的神经肌肉疾病患者带来首个获批药物，这些患者目前没有任何治疗选择，”表示。

Steve Hughes

史蒂夫·休斯

, M.D., chief medical officer at Avidity. 'We are very encouraged by the del-brax 2 mg/kg data thus far, demonstrating unprecedented and consistent reductions in DUX4-regulated genes, significant decreases in novel circulating biomarker and creatine kinase, trends of functional improvement, and favorable safety and tolerability, and look forward to sharing additional data as well as other key milestones in the second quarter of this year.'.

Avidity的首席医学官M.D.表示：“迄今为止，del-brax 2 mg/kg的数据让我们备受鼓舞，显示出对DUX4调控基因前所未有的持续减少、新型循环生物标志物和肌酸激酶显著降低、功能改善的趋势，以及良好的安全性和耐受性。我们期待在第二季度分享更多数据及其他关键里程碑。”

Avidity is on track to deliver multiple updates from the del-brax program in Q2 including:

Avidity 正在按计划于第二季度交付来自 del-brax 项目的多项更新，包括：

Regulatory alignment on a potential accelerated approval path in the U.S. for the ongoing FORTITUDE biomarker cohort;

美国对正在进行的FORTITUDE生物标志物队列潜在加速批准路径的监管一致性；

Regulatory alignment on the design of the global Phase 3 trial as well as initiation of the trial; and

全球三期试验设计的监管协调以及试验的启动；和

Topline data from the dose escalation cohorts in the FORTITUDE trial.

FORTITUDE试验中剂量递增队列的初步数据。

Del-brax is the first investigational therapy designed to treat the underlying cause of FSHD by directly targeting the mRNA transcript of the disease-causing gene, double homeobox 4 (DUX4). Currently, there are no approved therapies for the treatment of FSHD, a rare, hereditary disorder marked by life-long, relentless loss of muscle function, significant pain, fatigue, and progressive disability.

德尔布雷克斯（Del-brax）是首个旨在通过直接靶向致病基因双重同源框4（DUX4）的mRNA转录本来治疗面肩肱型肌营养不良症（FSHD）根本原因的在研疗法。目前，尚无获批用于治疗FSHD的疗法。FSHD是一种罕见的遗传性疾病，其特征是终生持续的肌肉功能丧失、显著的疼痛、疲劳和进行性残疾。

FSHD affects approximately 45,000 to 87,000 people in .

FSHD影响了大约45,000到87,000人。

the United States

美国

and European Union.

和欧洲联盟。

About the Phase 1/2 FORTITUDE™ trial

关于1/2期FORTITUDE™试验

The FORTITUDE™ trial is a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial designed to evaluate single and multiple doses of delpacibart braxlosiran or

FORTITUDE™ 试验是一项随机、安慰剂对照、双盲的 1/2 期临床试验，旨在评估单剂量和多剂量的 delpacibart braxlosiran 或

del-brax

删除-brax

in 90 participants with facioscapulohumeral muscular dystrophy (FSHD). FORTITUDE is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of del-brax administered intravenously. Activity of del-brax is being assessed using key biomarkers, including DUX4-regulated muscle and circulating biomarkers and magnetic resonance imaging (MRI) measures of muscle volume and composition.

在90名面肩肱型肌营养不良症（FSHD）参与者中。FORTITUDE正在评估静脉注射del-brax的安全性、耐受性、药代动力学和药效学。del-brax的活性正在通过关键生物标志物进行评估，包括DUX4调控的肌肉和循环生物标志物，以及肌肉体积和组成的磁共振成像（MRI）测量。

Though the Phase 1/2 trial is not statistically powered to assess functional benefit, it explores the clinical activity of del-brax including measures of mobility and muscle strength as well as patient reported outcomes and quality of life measures..

尽管 1/2 期试验并未设置统计学效力来评估功能性获益，但它探索了 del-brax 的临床活性，包括运动能力和肌肉力量的测量，以及患者报告的结果和生活质量指标。

The trial has a total of three dose cohorts. The first two dose escalation cohorts evaluated 2 mg/kg or 4 mg/kg of del-brax versus placebo and were designed to assess safety as well as inform the dose and dose regimen of del-brax for additional studies. Avidity has completed enrollment in the dose escalation cohorts and identified 2 mg/kg every six weeks of del-brax as the dose for future clinical trials..

该试验共有三个剂量组。前两个剂量递增组评估了2 mg/kg或4 mg/kg的del-brax与安慰剂的安全性，并旨在确定del-brax的剂量和给药方案以用于进一步研究。Avidity已完成剂量递增组的入组，并确定每六周2 mg/kg的del-brax作为未来临床试验的剂量。

The third, ongoing biomarker cohort in the FORTITUDE trial is designed for a potential accelerated approval path in the U.S. It is assessing the impact of del-brax 2 mg/kg every six weeks versus placebo for 12 months in people living with FSHD, ages 16-70. The primary endpoints of the study cohort are changes in DUX4-regulated gene expression and DUX4-regulated circulating biomarker.

FORTITUDE试验中第三个正在进行的生物标志物队列旨在为美国潜在的加速审批路径而设计。该队列评估了每六周给予del-brax 2 mg/kg与安慰剂在16至70岁FSHD患者中为期12个月的影响。研究队列的主要终点是DUX4调控基因表达和DUX4调控循环生物标志物的变化。

Enrollment in the biomarker cohort is complete..

生物标志物队列的注册已完成。

Participants who complete FORTITUDE have the option to enroll in the ongoing FORTITUDE open-label extension (FORTITUDE-OLE™) study evaluating the long-term safety and tolerability of del-brax in participants living with FSHD. For more information about the FORTITUDE trial, visit the

完成FORTITUDE的参与者可以选择加入正在进行的FORTITUDE开放标签扩展（FORTITUDE-OLE™）研究，该研究评估了del-brax在FSHD患者中的长期安全性和耐受性。有关FORTITUDE试验的更多信息，请访问

FORTITUDE study

坚定研究

website or visit

网站或访问

http://www.clinicaltrials.gov

http://www.clinicaltrials.gov

and search for NCT05747924.

搜索NCT05747924。

About the Phase 2 FORTITUDE-OLE™ trial

关于第二阶段的FORTITUDE-OLE™试验

FORTITUDE-OLE™ is an open-label, multi-center trial designed to evaluate the long-term safety and tolerability of delpacibart braxlosiran or

FORTITUDE-OLE™ 是一项开放标签、多中心试验，旨在评估德帕西巴特布拉克索利兰的长期安全性和耐受性。

del-brax

删除-brax

in participants with facioscapulohumeral muscular dystrophy (FSHD) who were previously enrolled in the Phase 1/2 FORTITUDE™ trial. This trial will continue to evaluate the safety, tolerability, PK, PD, and efficacy of del-brax in participants who enrolled in the randomized, placebo-controlled, Phase 1/2 FORTITUDE clinical trial.

既往参与过 1/2 期 FORTITUDE™ 试验的面肩肱型肌营养不良症 (FSHD) 受试者。本试验会继续评估 del-brax 在参与随机、安慰剂对照的 1/2 期 FORTITUDE 临床试验的受试者中的安全性、耐受性、药代动力学 (PK)、药效学 (PD) 和疗效。

Participants who enroll in the FORTITUDE-OLE study will receive del-brax regardless of whether they received active treatment or placebo in the FORTITUDE study. The total duration of active treatment with del-brax in the FORTITUDE-OLE is approximately 24 months. Avidity may extend active treatment beyond 24 months at a future timepoint.

参加FORTITUDE-OLE研究的参与者无论在FORTITUDE研究中接受的是活性治疗还是安慰剂，都将获得del-brax。在FORTITUDE-OLE中，使用del-brax进行活性治疗的总时长约为24个月。Avidity可能会在未来的某个时间点将活性治疗延长至超过24个月。

For more information on the FORTITUDE-OLE study .

有关FORTITUDE-OLE研究的更多信息，请点击此处。

click here

点击这里

or visit

或访问

http://www.clinicaltrials.gov

http://www.clinicaltrials.gov

and search for NCT06547216.

搜索NCT06547216。

About Del-brax

关于Del-brax

Del-brax is designed to treat the underlying cause of FSHD, which is caused by the abnormal expression of a gene called double homeobox 4 or DUX4. The abnormal expression of DUX4 protein leads to changes in gene expression in muscle cells that are associated with the life-long, progressive loss of muscle function in patients with FSHD.

Del-brax旨在治疗FSHD的根本原因，该病因一个名为双同源盒4（DUX4）基因的异常表达而引起。DUX4蛋白的异常表达导致肌肉细胞中的基因表达发生变化，这些变化与FSHD患者终生的、进行性的肌肉功能丧失相关。

Del-brax aims to reduce the expression of DUX4 mRNA and DUX4 protein in muscles in people with FSHD. Del-brax consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DUX4 mRNA. Avidity reported positive initial del-brax 2 mg/kg data at four months from the Phase 1/2 FORTITUDE™ trial demonstrating unprecedented and consistent reductions of greater than 50% in DUX4 regulated genes, trends of functional improvement, and favorable safety and tolerability in people living with FSHD.

Del-brax 旨在减少FSHD患者肌肉中DUX4 mRNA和DUX4蛋白的表达。Del-brax由一种专有的单克隆抗体组成，该抗体结合转铁蛋白受体1（TfR1），并与靶向DUX4 mRNA的siRNA结合。Avidity在1/2期FORTITUDE™试验中报告了del-brax 2 mg/kg剂量四个月后的初步积极数据，数据显示DUX4调控基因的表达减少了超过50%，功能改善的趋势明显，并且在FSHD患者中表现出良好的安全性和耐受性。

Del-brax is currently in Phase 1/2 development as part of the FORTITUDE trial in individuals with FSHD. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted Orphan designation for del-brax and the FDA has granted del-brax Fast Track designation..

德尔布雷克斯（Del-brax）目前作为FORTITUDE试验的一部分，正在进行针对面肩肱型肌营养不良症（FSHD）患者的1/2期开发。美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）已授予德尔布雷克斯孤儿药资格，且FDA还授予其快速通道资格。

About Facioscapulohumeral Muscular Dystrophy (FSHD)

关于面肩肱型肌营养不良症 (FSHD)

Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive, and variable hereditary muscle-weakening condition marked by life-long, relentless loss of muscle function, significant pain, fatigue, and progressive disability. It is characterized by progressive and often asymmetric skeletal muscle loss that initially causes weakness in muscles in the face, shoulders, arms and trunk and progresses to weakness in muscles in the lower body.

面肩肱型肌营养不良症 (FSHD) 是一种罕见、渐进且变异的遗传性肌肉衰弱疾病，表现为终生不断的肌肉功能丧失、显著的疼痛、疲劳和逐渐加重的残疾。其特征是进行性且常不对称的骨骼肌萎缩，最初导致面部、肩部、手臂和躯干的肌肉无力，并逐渐发展为下半身肌肉的无力。

FSHD is an autosomal dominant disease caused by the aberrant expression of the DUX4 (double homeobox 4) gene in the skeletal muscle, which activates genes that are toxic to muscle cells and leads to a series of downstream events that result in skeletal muscle wasting and compromised muscle function.

FSHD是一种常染色体显性遗传病，由骨骼肌中DUX4（双同源框4）基因的异常表达引起，该基因激活对肌肉细胞有毒性的基因，并导致一系列下游事件，从而引发骨骼肌萎缩和肌肉功能受损。

Skeletal muscle weakness results in physical limitations throughout the whole body, including an inability to lift arms for more than a few seconds, loss of ability to show facial expressions and serious speech impediments. These symptoms cause many people affected by FSHD to become dependent on the use of a wheelchair for mobility.

骨骼肌无力导致全身出现身体限制，包括无法将手臂举起超过几秒钟、无法做出面部表情以及严重的语言障碍。这些症状导致许多患有FSHD的人依赖轮椅行动。

Currently, there are no approved treatments for people living with FSHD..

目前，尚无针对FSHD患者的获批治疗方案。

About Avidity

关于Avidity

Avidity Biosciences, Inc.'s mission is to profoundly improve people's lives by delivering a new class of RNA therapeutics - Antibody Oligonucleotide Conjugates (AOCs™). Avidity is revolutionizing the field of RNA with its proprietary AOCs, which are designed to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to address targets and diseases previously unreachable with existing RNA therapies.

Avidity Biosciences, Inc. 的使命是通过提供一类新型的RNA疗法——抗体寡核苷酸偶联物 (AOCs™)，极大地改善人们的生活。Avidity 正在利用其专有的AOCs革新RNA领域，这些AOCs旨在将单克隆抗体的特异性与寡核苷酸疗法的精准性相结合，以解决现有RNA疗法无法触及的靶点和疾病。

Utilizing its proprietary AOC platform, Avidity demonstrated the first-ever successful targeted delivery of RNA into muscle and is leading the field with clinical development programs for three rare neuromuscular diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD).

利用其专有的AOC平台，Avidity成功展示了首次将RNA靶向递送到肌肉，并在针对三种罕见神经肌肉疾病的临床开发项目中处于领先地位：1型肌强直性营养不良（DM1）、杜氏肌营养不良（DMD）和面肩肱型肌营养不良（FSHD）。

Avidity is also advancing two wholly-owned precision cardiology development candidates addressing rare genetic cardiomyopathies. In addition, Avidity is broadening the reach of AOCs with its advancing and expanding pipeline including programs in cardiology and immunology through key partnerships. Avidity is headquartered in .

Avidity还在推进两个全资拥有的精准心脏病学开发候选药物，针对罕见的遗传性心肌病。此外，Avidity正在通过关键合作伙伴关系，扩大其推进和扩展中的管线（包括心脏病学和免疫学项目）来拓宽AOC的覆盖范围。Avidity总部位于。

San Diego, CA.

加利福尼亚州圣迭戈。

For more information about our AOC platform, clinical development pipeline and people, please visit

如需更多关于我们AOC平台、临床开发管道和人员的信息，请访问

www.aviditybiosciences.com

www.aviditybiosciences.com

and engage with us on

并联系我们

LinkedIn

领英

and

和

X

X

.

。

Forward-Looking Statements

前瞻性声明

Avidity cautions readers that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the company's current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: Avidity's plans to present topline data from the dose escalation cohorts of the FORTITUDE study and the timing thereof; Avidity's plans to pursue an accelerated approval path for del-brax and the anticipation of regulatory alignment with such plans; the status of the FORTITUDE trial and cohorts therein, including but not limited to initiation, enrollment, design and goals; the ability for del-brax to achieve accelerated approval;  the characterization of data associated with del-brax and the FORTITUDE trial, the conclusions drawn therefrom, the impact of such data on the advancement of del-brax and its abilities to treat FSHD; and the possibility of del-brax becoming the first globally approved drug for FSHD..

Avidity提醒读者，本新闻稿中关于非历史事实的陈述属于前瞻性声明。这些声明基于公司当前的信念和预期。此类前瞻性声明包括但不限于以下内容的声明：Avidity计划在FORTITUDE研究的剂量递增队列中发布初步数据及其时间安排；Avidity计划寻求del-brax的加速审批路径以及对与该计划相关的监管一致性的预期；FORTITUDE试验及其队列的状态，包括但不限于启动、招募、设计和目标；del-brax实现加速审批的可能性；与del-brax和FORTITUDE试验相关的数据特征、从中得出的结论、此类数据对del-brax进展及其治疗FSHD能力的影响；以及del-brax可能成为全球首个获批用于治疗FSHD的药物的可能性。

The inclusion of forward-looking statements should not be regarded as a representation by Avidity that any of these plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Avidity's business and beyond its control, including, without limitation: the data and results produced in the FORTITUDE trial and FORTITUDE-OLE as of the most recent respective cutoff dates may not be indicative of final results, may not support BLA submissions or accelerated approvals, may not be satisfactory to the FDA and other regulators, and new analyses of existing data and results may produce different conclusions than established as of the date hereof; even if approved, Avidity may not be able to execute a successful product launch for del-brax; unexpected adverse side effects to, or inadequate efficacy of, del-brax that may delay or limit its development, regulatory approval and/or commercialization; later developments with the FDA and other global regulators that could be inconsistent with the feedback received to date; Avidity's approach to the discovery and development of product candidates based on its AOC™ platform is unproven and may not produce any products of commercial value; potential delays in the commencement, enrollment, data readouts and completion of clinical trials; Avidity's dependence on third parties in connection with clinical testing and product manufacturing; legislative, judicial and regulatory developments in .

前瞻性陈述的包含不应被视为Avidity对任何这些计划将会实现的承诺。由于Avidity业务中固有的风险和不确定性以及其无法控制的因素，实际结果可能与此新闻稿中列出的内容有所不同，包括但不限于：截至最近的截止日期，FORTITUDE试验和FORTITUDE-OLE中产生的数据和结果可能无法反映最终结果，可能不支持BLA提交或加速批准，可能无法令FDA和其他监管机构满意，并且对现有数据和结果的新分析可能得出与本文件日期之前确立的不同的结论；即使获得批准，Avidity可能无法成功推出del-brax产品；del-brax可能出现意外的不良副作用或疗效不足，从而可能延迟或限制其开发、监管批准和/或商业化；FDA及其他全球监管机构的后续发展可能与迄今为止收到的反馈不一致；Avidity基于其AOC™平台进行产品候选发现和开发的方法尚未得到验证，可能无法产生任何商业价值的产品；临床试验的启动、入组、数据读取和完成可能会出现潜在延迟；Avidity在临床测试和产品制造方面对第三方的依赖；立法、司法和监管的发展可能影响相关进程。

the United States

美国

and foreign countries; Avidity could exhaust its available capital resources sooner than it currently expects; and other risks described in Avidity's Annual Report on Form 10-K for the fiscal year ended

以及外国国家；Avidity可能比目前预期的更早耗尽其可用资本资源；以及Avidity年度报告表格10-K中描述的其他风险，截至本财政年度结束。

December 31, 2024

2024年12月31日

and subsequent filings with the SEC. Avidity cautions readers not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and the company undertakes no obligation to update such statements to reflect events that occur or circumstances that arise after the date hereof.

并随后向美国证券交易委员会提交文件。Avidity提醒读者不要过分依赖这些前瞻性声明，这些声明仅截至本日期有效，公司没有义务更新这些声明以反映本日期之后发生的事件或出现的情况。

All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995..

所有前瞻性声明均受此警示性声明的全面约束，该警示性声明是根据1995年《私人证券诉讼改革法案》的安全港条款作出的。

Investor Contact:

投资者联系人：

Kat Lange

凯特·兰格

(619) 837-5014

(619) 837-5014

investors@aviditybio.com

投资者@aviditybio.com

Media Contact:

媒体联系人:

(619) 837-5016

(619) 837-5016

media@aviditybio.com

媒体@aviditybio.com

SOURCE Avidity Biosciences, Inc.

来源：Avidity Biosciences, Inc.

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