Avidity Biosciences, Inc., a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs™), today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to delpacibart zotadirsen (del-zota) for the treatment of Duchenne muscular dystrophy (DMD) in people living with mutations amenable to exon 44 skipping (DMD44)..

Avidity Biosciences, Inc.，一家致力于提供一类新型RNA疗法（称为抗体寡核苷酸偶联物，AOCs™）的生物制药公司，今天宣布美国食品药品监督管理局 (FDA) 已授予delpacibart zotadirsen (del-zota) 突破性疗法认定，用于治疗适合外显子44跳跃（DMD44）突变的杜氏肌营养不良症 (DMD) 患者。

Del-zota is currently being assessed in the Phase 2 EXPLORE44 Open-Label Extension (EXPLORE44-OLE™) trial for people living with DMD44 and is the first of multiple AOCs the company is developing for DMD.

德尔佐塔目前正在进行针对DMD44患者的二期EXPLORE44开放标签扩展（EXPLORE44-OLE™）试验评估，是该公司为DMD开发的多个AOC中的第一个。

DMD is a rare genetic condition that is characterized by progressive muscle damage and weakness due to the loss of dystrophin protein that typically starts at a very young age. Del-zota is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to skeletal muscle and heart tissue to specifically skip exon 44 of the dystrophin gene and enable production of near-full length dystrophin. .

DMD是一种罕见的遗传病，其特征是由于抗肌萎缩蛋白的缺失导致进行性肌肉损伤和无力，通常在很小的时候就开始发病。Del-zota旨在将磷酰二胺吗啉代寡聚物（PMOs）递送到骨骼肌和心脏组织，以特异性跳过抗肌萎缩蛋白基因的第44号外显子，从而实现近全长抗肌萎缩蛋白的生产。

'Breakthrough Therapy designation further underscores the FDA's appreciation for the significant potential of del-zota to address the underlying cause of DMD44 and the urgent need to bring innovative treatment options to the DMD community,' said

“突破性疗法认定进一步凸显了FDA对del-zota解决DMD44根本原因的巨大潜力的认可，以及为DMD群体带来创新治疗方案的迫切需求，”

Steve Hughes

史蒂夫·休斯

, M.D., chief medical officer at Avidity. 'With the remarkable, consistent improvements we've seen in multiple biomarkers including dystrophin in the Phase 1/2 EXPLORE44 trial, we are focused on bringing del-zota to people living with DMD44 as quickly as possible and remain on track for our planned BLA submission at year end 2025.'.

Avidity的首席医疗官M.D.表示：“在1/2期EXPLORE44试验中，我们看到了包括dystrophin在内的多个生物标志物显著且一致的改善，我们将专注于尽快将del-zota带给DMD44患者，并计划在2025年底提交BLA。”

In the completed Phase 1/2 EXPLORE44

在已完成的第1/2阶段EXPLORE44

trial for people living with DMD44, del-zota demonstrated statistically significant increases in exon skipping, a substantial increase in dystrophin production, a significant and sustained reduction in creatine kinase levels to near normal and consistent favorable safety and tolerability. Avidity plans to present topline and functional data from the ongoing, fully enrolled Phase 2 EXPLORE44-OLE trial in the fourth quarter of 2025..

对于DMD44患者，del-zota在外显子跳跃方面表现出统计学上显著的增加，抗肌萎缩蛋白产量大幅提高，肌酸激酶水平显著且持续降低至接近正常，并且安全性和耐受性始终良好。Avidity计划在2025年第四季度公布正在进行的、已全部招募的二期EXPLORE44-OLE试验的主要数据和功能数据。

remains on track for a planned BLA submission at year end 2025.

仍然按计划在2025年底提交BLA。

Avidity's commercial preparations for a potential U.S. launch of del-zota in DMD44 following FDA approval are underway. Del-zota's anticipated launch sets the foundation for potential sequential launches of Avidity's additional neuromuscular programs for del-desiran in myotonic dystrophy type 1 (DM1) and del-brax in facioscapulohumeral muscular dystrophy (FSHD)..

Avidity公司正为在美国获得FDA批准后，可能推出的del-zota用于治疗DMD44做商业化准备。del-zota的预期上市为Avidity公司另外的神经肌肉项目奠定了潜在的连续发布基础，包括用于治疗1型肌强直性营养不良（DM1）的del-desiran和用于面肩肱型肌营养不良（FSHD）的del-brax。

Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s)..

突破性疗法指定是一个旨在加速用于治疗严重疾病药物的开发和审查的过程，初步临床证据表明该药物可能在临床上显著的终点上显示出比现有疗法更大的改善。

In addition to receiving Breakthrough Therapy designation, del-zota has previously been granted Orphan designation by the FDA and the European Medicines Agency (EMA) and Rare Pediatric Disease and Fast Track designations by the FDA for the treatment of DMD44.

除了获得突破性疗法认定外，del-zota 之前还获得了 FDA 和欧洲药品管理局 (EMA) 的孤儿药认定，以及 FDA 授予的罕见儿科疾病和快速通道认定，用于治疗 DMD44。

About the EXPLORE44

关于EXPLORE44

Phase 1/2 Trial

1/2期试验

The EXPLORE44

探索44

trial was a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial

试验是一项随机、安慰剂对照、双盲的 1/2 期临床试验

that enrolled 26 participants with Duchenne muscular dystrophy mutations amenable to exon 44 skipping (DMD44). The study was designed

招募了26名适合外显子44跳跃的杜氏肌营养不良症突变患者（DMD44）。该研究设计为

to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single and multiple ascending doses of del-zota

评估单次和多次递增剂量的del-zota的安全性、耐受性、药代动力学和药效学效应

(formerly AOC 1044)

（原AOC 1044）

administered intravenously

静脉注射

in healthy volunteers and participants living with DMD44

在健康志愿者和患有DMD44的参与者中

. The EXPLORE44 trial assessed exon skipping and dystrophin protein levels in participants with DMD44. Participants with DMD44 had the option to enroll into

EXPLORE44 试验评估了 DMD44 参与者的外显子跳跃和肌营养蛋白水平。DMD44 参与者可以选择加入

EXPLORE44-OLE™,

探索44-OLE™，

an open-label extension study,

一项开放标签扩展研究，

at the end of the post-treatment period

在治疗期结束时

. For more information about the EXPLORE44 trial, visit the

如需更多关于EXPLORE44试验的信息，请访问

EXPLORE44 study

探索44研究

website or visit

网站或访问

https://www.clinicaltrials.gov

https://www.clinicaltrials.gov

and search for NCT05670730.

搜索NCT05670730。

About the Phase 2 EXPLORE44-OLE™ Study

关于第2阶段EXPLORE44-OLE™研究

EXPLORE44-OLE™ is an open-label, multi-center trial designed to evaluate the long-term safety, tolerability,

EXPLORE44-OLE™ 是一项开放标签、多中心试验，旨在评估长期安全性和耐受性，

pharmacokinetics

药代动力学

pharmacodynamic effects

药效学作用

and efficacy of

和功效

del-zota

德尔佐塔

in participants with DMD44. Enrollment has been completed in the EXPLORE44-OLE study, with 23 participants who were previously enrolled in the Phase 1/2 EXPLORE44

在DMD44患者中。EXPLORE44-OLE研究的入组已经完成，共有23名之前参与过1/2期EXPLORE44研究的参与者。

trial and 16 participants who directly enrolled in the EXPLORE44-OLE study. Participants in the EXPLORE44-OLE study will receive 5 mg/kg of

试验和16名直接参与EXPLORE44-OLE研究的参与者。EXPLORE44-OLE研究中的参与者将接受5毫克/千克的

del-zota

德尔佐塔

every six weeks. The total duration of active treatment with

每六周。积极治疗的总持续时间

del-zota

德尔佐塔

in the EXPLORE44-OLE study is approximately 24 months. Once participants have completed active treatment, there will be a three-month safety follow-up period. Avidity may extend active treatment beyond 24 months at a future timepoint. For more information on this study click

在EXPLORE44-OLE研究中的预计持续时间约为24个月。一旦参与者完成积极治疗，将有一个为期三个月的安全性随访期。Avidity可能会在未来某个时间点延长超过24个月的积极治疗。欲了解有关本研究的更多信息，请点击。

About Duchenne muscular dystrophy (DMD)

关于杜氏肌营养不良症 (DMD)

Duchenne muscular dystrophy (DMD) causes a lack of functional dystrophin that leads to stress and tears of muscle cell membranes, resulting in muscle cell death and the progressive loss of muscle function. The dystrophin protein maintains the integrity of muscle fibers and acts as a shock absorber through its role as the foundation of a group of proteins that connects the inner and outer elements of muscle cells.

杜氏肌营养不良症 (DMD) 导致功能性肌营养不良蛋白缺乏，从而引发肌细胞膜的应力和撕裂，导致肌细胞死亡和肌肉功能的逐渐丧失。肌营养不良蛋白通过作为连接肌肉细胞内外元素的蛋白质群的基础，维持肌纤维的完整性并起到减震器的作用。

People living with DMD suffer from progressive muscle weakness that typically starts at a very young age. Over time, people with Duchenne will develop problems walking and breathing, and eventually, the heart and respiratory muscles will stop working. Those living with the condition often require special aid and assistance throughout their lives and have significantly shortened life expectancy.

杜氏肌营养不良症患者会遭受进行性肌肉无力的折磨，这种症状通常在很小的时候就开始了。随着时间的推移，患有杜氏肌营养不良症的人会出现行走和呼吸问题，最终心脏和呼吸肌将停止工作。患有此病的人往往在其一生中需要特殊的援助和帮助，并且预期寿命显著缩短。

While there are treatments approved to treat people with DMD, there remains a very high unmet need. DMD is a monogenic, X-linked, recessive disease that primarily affects males, with one in 3,500 to 5,000 boys born worldwide having Duchenne..

虽然已有获批的治疗方法用于治疗DMD患者，但仍然存在非常高的未满足需求。DMD是一种单基因、X连锁的隐性遗传病，主要影响男性，全球每3500至5000名男婴中就有一人患有杜氏肌营养不良症。

About del-zota

关于德尔佐塔

Del-zota is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to skeletal muscle and heart tissue to specifically skip exon 44 of the dystrophin gene to enable dystrophin production in people living with Duchenne muscular dystrophy with mutations amenable to exon 44 skipping (DMD44).

德尔佐塔（Del-zota）旨在将磷酰二胺吗啉代寡聚物（PMOs）递送到骨骼肌和心脏组织，以特异性跳过抗肌萎缩蛋白基因的第44号外显子，从而在适合外显子44跳跃的杜氏肌营养不良症（DMD44）患者中促进抗肌萎缩蛋白的生成。

DMD is characterized by progressive muscle degeneration and weakness due to alterations of a protein called dystrophin that protects muscle cells from injury during contraction. Del-zota consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a PMO targeting exon 44.

DMD 的特征是由于一种保护肌肉细胞在收缩过程中免受损伤的蛋白质——肌营养不良蛋白（dystrophin）发生变异，导致进行性肌肉退化和无力。Del-zota 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)，并与靶向第 44 号外显子的 PMO 结合。

The Phase 1/2 EXPLORE44® trial of del-zota has been completed, and the EXPLORE44 Open-Label Extension trial (EXPLORE44-OLE™) of del-zota is currently ongoing. Topline data from the completed del-zota Phase 1/2 EXPLORE44 trial demonstrated unsurpassed delivery of PMOs to skeletal muscle, robust increases in dystrophin production, significant increases in exon 44 skipping, and significant and sustained decreases of creatine kinase levels to near normal in people living with DMD44.

del-zota的1/2期EXPLORE44®试验已完成，del-zota的EXPLORE44开放标签扩展试验（EXPLORE44-OLE™）正在进行中。已完成的del-zota 1/2期EXPLORE44试验的初步数据显示，PMOs向骨骼肌的递送效果无与伦比，抗肌萎缩蛋白生成显著增加，第44号外显子跳跃显著提高，并且在患有DMD44的人群中，肌酸激酶水平显著且持续降低至接近正常。

Del-zota has received Rare Pediatric Disease, Orphan Drug, Fast Track and Breakthrough Therapy designations by the U.S. Food and Drug Administration (FDA) and Orphan designation by the European Medicines Agency (EMA)..

德尔佐塔已获得美国食品药品监督管理局（FDA）授予的罕见儿科疾病、孤儿药、快速通道和突破性疗法资格，以及欧洲药品管理局（EMA）授予的孤儿药资格。

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. 的使命是通过交付一类新型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，以针对现有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 neuromusculardiseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD).

利用其专有的AOC平台，Avidity成功实现了首次将RNA靶向递送到肌肉，并在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还在推进两种针对罕见遗传性心肌病的全资精准心脏病学开发候选药物。此外，

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 San Diego, CA. For more information about our AOC platform, clinical development pipeline and people, please visit

Avidity正在通过其不断推进和扩展的研发管线，包括在心脏病学和免疫学领域的项目，通过关键合作伙伴关系来扩大AOC的影响力。Avidity总部位于加利福尼亚州圣地亚哥。如需了解更多关于我们AOC平台、临床开发管线和团队的信息，请访问