A Randomized, Placebo-Controlled, Multiple Ascending Dose Study Assessing Safety, Tolerability, Pharmacodynamics, Efficacy, and Pharmacokinetics of DYNE-101 Administered to Participants With Myotonic Dystrophy Type 1

The primary purpose of the study is to evaluate the safety and tolerability of multiple intravenous (IV) doses of DYNE-101 administered to participants with Myotonic Dystrophy Type 1 (DM1).
The study consists of 4 periods: A Screening Period (up to 8 weeks), a multiple-ascending dose (MAD) Placebo-Controlled Period (24 weeks), a Treatment Period (24 weeks) and a Long-Term Extension (LTE) Period (96 weeks).

开始日期2022-09-05

申办/合作机构

Dyne Therapeutics, Inc.

100 项与 DYNE-101 相关的专利（医药）

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项与 DYNE-101 相关的文献（医药）

2023-01-09·Drug discovery today

The myotonic dystrophy type 1 drug development pipeline: 2022 edition.

Review

作者: Marta Pascual-Gilabert ; Ruben Artero ; Arturo López-Castel

The beginning of the 20th decade has witnessed an increase in drug development programs for myotonic dystrophy type 1 (DM1). We have collected nearly 20 candidate drugs with accomplished preclinical and clinical phases, updating our previous drug development pipeline review with new entries and relevant milestones for pre-existing candidates. Three interventional first-in-human clinical trials got underway with distinct drug classes, namely AOC 1001 and DYNE-101 nucleic acid-based therapies, and the small molecule pitolisant, which joins the race toward market authorization with other repurposed drugs, including tideglusib, metformin, or mexiletine, already in clinical evaluation. Furthermore, newly disclosed promising preclinical data for several additional nucleic-acid therapeutic candidates and a CRISPR-based approach, as well as the advent into the pipeline of novel therapeutic programs, increase the plausibility of success in the demanding task of providing valid treatments to patients with DM1.

项与 DYNE-101 相关的新闻（医药）

2023-09-20

·BioSpace

Dyne Therapeutics Receives FDA Orphan Drug Designation for DYNE-101 for the Treatment of Myotonic Dystrophy Type 1

- On Track to Report Initial Data from the Global, Multiple Ascending Dose Phase 1/2 ACHIEVE Clinical Trial in the Second Half of 2023 - WALTHAM, Mass., Sept. 20, 2023 (GLOBE NEWSWIRE) -- Dyne Therapeutics, Inc. (Nasdaq: DYN), a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for DYNE-101 for the treatment of myotonic dystrophy type 1 (DM1). DYNE-101 is being evaluated in the Phase 1/2 global ACHIEVE clinical trial with initial data on safety, tolerability and splicing from the multiple ascending dose, placebo-controlled portion of the trial anticipated in the second half of 2023. “Receiving FDA orphan drug designation for DYNE-101 underscores the importance of bringing new treatment options to people living with DM1, a rare, devastating disease with no approved therapies. We believe DYNE-101 has the potential to be a transformative therapy which is why we designed the ACHIEVE trial to be registrational,” said Wildon Farwell, M.D., MPH, chief medical officer of Dyne. “We recognize the sense of urgency within the DM1 community and look forward to sharing initial data from the ACHIEVE trial.” Orphan drug designation is granted by the FDA to drugs or biologics intended for treatment, prevention or diagnosis of a rare disease or condition that affects fewer than 200,000 people in the United States. Under the Orphan Drug Act, orphan drug designation qualifies a company for incentives, including tax credits, exemptions from certain FDA fees for clinical trials, and the potential for seven years of market exclusivity following drug approval. About DYNE-101 DYNE-101 is an investigational therapeutic being evaluated in the Phase 1/2 global ACHIEVE clinical trial for people living with myotonic dystrophy type 1 (DM1). DYNE-101 consists of an antigen-binding fragment antibody (Fab) conjugated to an antisense oligonucleotide (ASO) and is designed to enable targeted muscle tissue delivery with the goal of reducing toxic DMPK RNA in the nucleus, releasing splicing proteins, allowing normal mRNA processing and translation of normal proteins, and potentially stopping or reversing the disease. Dyne has generated comprehensive preclinical data supporting its DM1 program, including reduction of nuclear foci and correction of splicing in patient cells, robust knockdown of toxic human nuclear DMPK RNA and correction of splicing in a novel in vivo model developed by Dyne, and reversal of myotonia in a disease model. In non-human primates, DYNE-101 demonstrated a favorable safety pro achieved enhanced muscle distribution as evidenced by significant reduction in wild-type DMPK RNA. DYNE-101 was also granted orphan drug designation by the European Medicines Agency for the treatment of DM1. About ACHIEVE ACHIEVE is a Phase 1/2 global clinical trial evaluating DYNE-101, consisting of a 24-week multiple ascending dose (MAD) randomized placebo-controlled period, a 24-week open-label extension and a 96-week long-term extension. The trial, which is designed to be registrational, is expected to enroll approximately 72 adult patients with DM1 who are 18 to 49 years of age. The primary endpoints are safety and tolerability, with secondary endpoints of pharmacokinetics and pharmacodynamics, including change from baseline in splicing, as well as measures of muscle strength and function. Dyne anticipates reporting initial data from the MAD placebo-controlled portion of the ACHIEVE trial on safety, tolerability and splicing in the second half of 2023. For more information on the ACHIEVE trial, visit (NCT05481879). About Myotonic Dystrophy Type 1 (DM1) DM1 is a rare, progressive, genetic disease that affects skeletal, cardiac and smooth muscle. It is a monogenic, autosomal dominant disease caused by an abnormal trinucleotide expansion in a region of the DMPK gene. This expansion of CTG repeats causes toxic RNA to cluster in the nucleus, forming nuclear foci and altering the splicing of multiple proteins essential for normal cellular function. This altered splicing, or spliceopathy, results in a wide range of symptoms. People living with DM1 typically experience progressive weakness of major muscle groups, which can affect mobility, breathing, heart function, speech, digestion and vision as well as cognition. DM1 is estimated to affect more than 40,000 people in the United States and over 74,000 people in Europe, but there are currently no approved disease-modifying therapies. About Dyne Therapeutics Dyne Therapeutics is a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases. With its proprietary FORCE™ platform, Dyne is developing modern oligonucleotide therapeutics that are designed to overcome limitations in delivery to muscle tissue seen with other approaches. Dyne has a broad pipeline for serious muscle diseases, including clinical programs for myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) and a preclinical program for facioscapulohumeral muscular dystrophy (FSHD). For more information, please visit , and follow us on Twitter, LinkedIn and Facebook. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Dyne’s strategy, future operations, prospects and plans, objectives of management, the potential of the FORCE platform, the anticipated timelines for reporting data from the DYNE-101 clinical trial, the trial design of the DYNE-101 clinical trial, and any potential benefit from receiving orphan drug designation, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “on track,”, “plan,” “predict,” “project,” “potential,” “should,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Dyne may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; the timing of and Dyne’s ability to initiate and enroll patients in clinical trials; whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials; as well as the risks and uncertainties identified in Dyne’s filings with the Securities and Exchange Commission (SEC), including the Company’s most recent Form 10-Q and in subsequent filings Dyne may make with the SEC. In addition, the forward-looking statements included in this press release represent Dyne’s views as of the date of this press release. Dyne anticipates that subsequent events and developments will cause its views to change. However, while Dyne may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Dyne’s views as of any date subsequent to the date of this press release. Contacts: Investors Dyne Therapeutics Amy Reilly areilly@dyne-tx.com 857-341-1203 Media Dyne Therapeutics Stacy Nartker snartker@dyne-tx.com 781-317-1938

孤儿药寡核苷酸临床研究

2023-08-11

·生物制品圈

偶联不止ADC，抗体-寡核苷酸偶联物(AOC)盘点

前言过去几年，由于寡核苷酸具有调控基因表达的独特优势，基于寡核苷酸的基因疗法开发如火如荼。寡核苷酸即长度在20至60单位之间的短DNA或RNA低聚物，它们可以合成或以单链（ss）或双链（ds）低聚物的形式天然存在。寡核苷酸药物的问世拓宽了疾病治疗的手段与边界，为许多疾病治疗带来新的希望。不过，由于寡核苷酸分子量大、亲水性高且带负电，未经修饰难以透过细胞膜和血脑屏障，同时易被核酸酶降解、稳定性差，其递送问题成为了寡核苷酸药物研发的瓶颈。目前已获批的核酸药物递送系统主要是脂质体递送系统和GalNAc递送系统，但两者均无法进行肝脏以外的药物靶向递送。而抗体-寡核苷酸偶联物（Antibody-oligonucleotide conjugates,AOC）有望解决该难题。AOC的开发建立在抗体药物偶联物（ADC）的成功基础上。ADC的成功奥秘在于药物结构的设计，受此启发，有多种偶联药物利用这种方式提高靶向性或者扩大适应症范围，这也促成了AOC的诞生与发展。在ADC概念的影响下，AOC已成为靶向寡核苷酸药物递送的潜在载体。具体来说，AOC是一类抗体与寡核苷酸偶联合成的新型嵌合生物分子。作为新型药物，AOC通过将单抗和寡核苷酸偶联，达到有效的靶向治疗能力，相比寡核苷酸具有精准靶向和更好的药代动力学特性。2021年11月，AOC先驱Avidity Biosciences的抗体寡核苷酸偶联物AOC1001的I期临床试验完成首例患者给药，标志着全球首款AOC药物进入临床试验。此后，其他公司的AOC项目在2022年陆续进入临床。那么，AOC药物发展到哪一步了？目前有哪些企业在布局？我们跟随发表在Nature Reviews Drug Discovery上的一篇文章Antibody–oligonucleotide conjugates enter the clinic，来一探究竟。本文分享几项AOC技术平台及临床进展，来自Avidity Biosciences、Tallac Therapeutics、Dyne Therapeutics、Denali Therapeutics和Gennao Bio，开发项目涵盖的适应症包括肌肉疾病、中枢神经系统疾病和肿瘤等。国内在AOC方向布局企业相对较少，以迦进生物为代表，走在前列。图注：在研AOC药物（来源：Nature Reviews Drug Discovery） 01 Avidity Biosciences（AOC 1001；I/II期；首个进入临床的AOC）Avidity Biosciences成立于2013年，总部位于美国加州拉荷亚市，是一家正在开创AOC疗法治疗遗传性肌肉疾病的生物医药公司。成立之初，Avidity设想通过抗体进行小干扰RNA（siRNA）-纳米颗粒的组织特异性递送，但并不顺利，因为抗体难以实现siRNA-纳米颗粒的有效输送。为了确保有效的荷载，研究人员将抗体直接与siRNA相偶联，AOC药物的设计便由此诞生。 ①AOC 1001是Avidity的主要候选产品，被开发用于治疗强直性肌营养不良1型（DM1），由专有的转铁蛋白受体1（TfR1）抗体与靶向强直性肌营养不良蛋白激酶（DMPK）mRNA的siRNA偶联而成，旨在通过降低DMPK相关mRNA的水平以解决DM1的根本病因。目前，Avidity正在开展AOC1001治疗DM1的I/II期MARINA和MARINA-OLE研究，AOC 1001也是第一个进入临床的AOC药物。②AOC 1044是一种外显子跳跃药物，可使外显子44跳跃的杜兴氏肌肉萎缩症（DMD）患者受益，该患者群占DMD的6%。AOC 1044旨在向骨骼肌和心脏组织提供磷酸二酰胺吗啉低聚物（PMO），从而恢复DMD基因的阅读框架，并使较小但仍有功能的肌营养不良蛋白得以产生。AOC 1044正在针对DMD44患者进行I/II 期临床试验评估，该试验旨在评估AOC 1044在健康志愿者和可跳过44号外显子的DMD患者中的安全性、药代动力学、耐受性和药效学特性。③AOC 1020是Avidity的另一款AOC药物。它由TfR1抗体与靶向DUX4 mRNA的siRNA偶联而成，被开发用于治疗面肩肱型肌营养不良症（FSHD）。FSHD是一种临床上常见的遗传性肌肉疾病之一，由骨骼肌中DUX4基因的异常表达引起，通过一系列下游事件导致骨骼肌萎缩和肌肉功能受损。图注：AOC 1020简介（来自：洞见conjugates）临床前数据显示，AOC1020可抑制DUX4 mRNA的表达，从而降低DUX4蛋白水平，减少下游基因表达。目前AOC1020正在FSHD成人患者中开展I/II期关键试验FORTITUDE研究。图注：Avidity研发管线（来自：Avidity官网） 02 Tallac Therapeutics（TAC-001；I/II期；启动先天性免疫）Tallac Therapeutics总部位于加州，其药物开发重点是启动先天免疫来识别和摧毁癌细胞。因此，Tallac选择的治疗有效载荷是含有CpG基序的合成寡核苷酸，能模拟激活先天免疫靶点TLR9的细菌指纹(bacterial fingerprints)。 TAC-001是Tallac的一种重要的候选药物，它是一种由强效的T-CpG与CD22抗体结合的AOC，通过与CD22结合将T-CpG递送给B细胞，进而导致TAC-001的内化以及TLR9信号、B细胞激活，产生一系列免疫反应。TAC-001引发的先天性和适应性免疫反应在检查点抑制剂耐药和难治性肿瘤模型中显示出强大、治愈和持久的单药抗肿瘤活性。TAC-001目前处于I/II期临床阶段。Tallac未来的项目可能会包含具有不同靶点的抗体、不同的Fc参与水平、linker和CpG有效载荷。 03 Dyne Therapeutics（DYNE-101；I/II期；Fab+ASO） Dyne成立于2017年12月，产品线主要聚焦三大罕见肌肉疾病：DM1、DMD和FSHD。Dyne在AOC药物设计上，主要靶向转铁蛋白受体1（TfR1），发挥靶向作用的是抗原结合片段（Fab）而非全长抗体。Dyne认为全长抗体会诱导TfR1的降解，进而降低药物作用和铁吸收过程中的受体可用性。较小的抗原结合片段意味着每剂量药物的蛋白质负荷较低，在耐受性上可能更有利。Dyne的AOC药物使用了可断裂的linker。在治疗载荷上，Dyne计划使用siRNA、反义寡核苷酸（ASO）等。图注：Dyne研发管线（来自：Dyne官网）Dyne的核心候选药物DYNE-101由Fab与ASO偶联而成，以实现靶向肌肉组织递送，目的是减少细胞核中的毒性DMPK RNA，释放剪接蛋白，允许正常的mRNA加工和翻译正常蛋白质，并可能阻止或逆转疾病。Dyne已经获得了全面的临床前数据支持其DYNE-101项目，包括在DM1患者细胞中减少核焦点和纠正剪接，在Dyne开发的新型体内模型中稳定敲低人类核内毒性DMPK RNA和纠正剪接，以及在疾病模型中逆转肌强直性。在非人灵长类动物中，DYNE-101显示出良好的安全性，并通过显著减少野生型DMPK RNA证明了其增强的肌肉分布。2023年5月，欧洲药品管理局(EMA)授予DYNE-101孤儿药资格认定。目前Dyne正在针对DYNE-101治疗成人DM1的ACHIEVE的I/II期临床试验进行评估。 04 Denali Therapeutics（DNL310；II/III期；非靶向性的ASO）Denali Therapeutics是一家专注于神经退行性疾病的生物制药公司，公司开发了专有的转运载体（TV）技术平台，能够使治疗用生物大分子更有效地穿过血脑屏障，包括酶、抗体、蛋白质和寡核苷酸。另外，Denali将TfR1视为通往大脑的门户。排列在血脑屏障中的细胞表达着TfR1，因此，TfR1是寡核苷酸、蛋白质和抗体药物进入中枢神经系统的理想途径。图注：Denali研发管线（来自：Denali官网）Denali初次尝试靶向TfR1使用的是DNL310。这是一款由人艾杜糖-2-硫酸酯酶（IDS）与Denali的酶转运载体（ETV）结合的ASO药物，被开发用来治疗II型黏多糖贮积症（MPS II）。这是一种罕见的神经退行性溶酶体贮积症，是由于编码IDS的基因出现突变引起。IDS酶活性的降低或丧失导致糖胺聚糖（GAG）在溶酶体的积累，从而引起溶酶体功能障碍和神经退行性病变。患者自两岁起便会出现症状，包含内脏功能失调、关节硬化、听力损失、生长阻碍以及神经认知相关症状，存在极大的医疗未竟需求。DNL310被设计为可以递送IDS蛋白至包含脑部的全身细胞与组织的溶酶体中，以对GAG进行分解，从而达到治疗MPS II的目的。今年6月，公司公布了DNL310用于MPS II治疗的I/II期临床结果。数据显示，与基线相较，MPS II患者血清中的神经丝蛋白轻链（NfL）水平显著减少达64%。目前DNL310的临床II/III期试验正在全球进行中。值得注意的是，目前Denali开发的抗体载体的抗原结合臂是非靶向性的，Denali考虑在后续的药物中增加对特定细胞类型的靶向。 05 Gennao Bio(GMAB-7001；临床前；首个无linker AOC)Gennao Bio位于新泽西州，由耶鲁大学的Peter Glazer教授基于他对狼疮自身抗体3E10的研究所创立。Gennao Bio正在探索无linker的AOC。 Gennao Bio开发了其专有的非病毒GMAB平台技术，它使用新型细胞穿透抗体特异性地将核酸有效载荷递送到选定的细胞，同时明显避免内吞途径。靶点为肿瘤细胞和骨骼肌上表达的核苷转运蛋白（ENT2）。其候选药物GMAB-7001是首个无linker的AOC，在胰腺癌小鼠模型试验中，GMAB-7001可长期提升肿瘤浸润淋巴细胞（CD45+、CD8+、CD4+和CD19+细胞等）水平，并且可穿透中枢神经系统，将颅内肿瘤负担降低50%，并防止脊柱转移。 06 国内相关：迦进生物首批布局AOC国内在AOC布局企业相对较少，迦进生物是国内首批从事小核酸偶联药物研发的生物科技公司，将小核酸以偶联的方式实现肝外递送，填补了该细分领域的国内空缺。迦进生物的先导产品 CGB1001 为针对 1 型强直性肌营养不良症（DM1）的抗体-siRNA 偶联药物，预计将在 2023 年启动新药临床研究审批（IND）相关工作。图注：迦进生物相关管线独特的是，迦进生物使用的是‘定点偶联’工艺，开发的小核酸偶联药物在收率、纯度、均一性以及体内/外活性方面比‘随机偶联’工艺开发的药物实现了大规模的提升，Avidity Biosciences的主要候选产品AOC 1001（第一款上临床的AOC）为随机偶联方式。图注：定点偶联技术改善CMC结语小核酸药物与小分子化药和抗体药相比，具有显著优势。不过小核酸药物整体研发仍处于早期阶段，其技术难点仍有待多层突破，尤其是靶向递送和有效作用需加快研发。在肝靶向以外，小核酸药物迈向更广泛的组织类型中仍有待于递送工具的拓展。AOC作为一种简便､特异性高､不良反应小的组合式创新递送手段，提供了更多的可能性，期待AOC在多种疾病治疗领域取得更多突破。参考：1.Antibody–oligonucleotide conjugates enter the clinic. Nature Reviews Drug Discovery.2.https://www.biospace.com/article/releases/dyne-therapeutics-receives-european-medicines-agency-ema-orphan-drug-designation-for-dyne-101/?s=63.3.Denali Therapeutics Announces Robust Reduction in Neurofilament Light (NfL) with DNL310 (ETV:IDS) Treatment in MPS II (Hunter Syndrome). Retrieved June 20, 2023 from https://www.denalitherapeutics.com/investors/press-release?id=9391&type=api.

寡核苷酸临床1期抗体药物偶联物siRNA信使RNA

2023-08-03

·BioSpace

Dyne Therapeutics Reports Second Quarter 2023 Financial Results and Business Highlights

- On Track to Report Initial Data from ACHIEVE Clinical Trial of DYNE-101 in DM1 and DELIVER Clinical Trial of DYNE-251 in DMD During the Second Half of 2023 - WALTHAM, Mass., Aug. 03, 2023 (GLOBE NEWSWIRE) -- Dyne Therapeutics, Inc. (Nasdaq: DYN), a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases, today reported financial results for the second quarter of 2023 and business highlights. “This is an exciting time for the entire Dyne team as we continue to enroll and dose patients in our ACHIEVE and DELIVER trials and are on track to report our first clinical data from both during the second half of this year, including evaluating important biomarkers of splicing in DM1 and dystrophin in DMD,” said Joshua Brumm, president and chief executive officer of Dyne. “In addition to progressing our clinical programs, we were also pleased to present preclinical data at ASGCT in May demonstrating the FORCE™ platform achieved TfR1-mediated delivery to the CNS, building on previous work showing delivery to skeletal, smooth and cardiac muscle in multiple well-validated preclinical models. CNS symptoms contribute significantly to the burden of neuromuscular disease, and we look forward to further exploring this application of the FORCE platform. Our commitment to advancing the treatment and care of individuals living with rare muscle diseases continues to drive our efforts with a sense of urgency.” Business Highlights Enrollment continues in ACHIEVE, a Phase 1/2 global clinical trial evaluating DYNE-101 in adult patients with myotonic dystrophy type 1 (DM1). ACHIEVE, which is designed to be a registrational trial, consists of a 24-week multiple ascending dose (MAD), randomized, placebo-controlled period, a 24-week open-label extension and a 96-week long-term extension. The primary endpoints are safety and tolerability, with secondary endpoints of pharmacokinetics and pharmacodynamics, including change from baseline in splicing, as well as measures of muscle strength and function. Enrollment continues in DELIVER, a Phase 1/2 global clinical trial evaluating DYNE-251 in males with Duchenne muscular dystrophy (DMD) who have mutations amenable to exon 51 skipping. DELIVER, which is designed to be a registrational trial, consists of a 24-week MAD, randomized, placebo-controlled period, a 24-week open-label extension and a 96-week long-term extension. The primary endpoints are safety, tolerability and change from baseline in dystrophin levels as measured by Western blot. Secondary endpoints include measures of muscle function, exon skipping and pharmacokinetics. New preclinical data were featured in an oral presentation at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting in May 2023 demonstrating the FORCE platform achieved delivery to the central nervous system (CNS) in non-human primates and robust pharmacological effects in the brain in a model of DM1. The European Medicines Agency (EMA) granted orphan drug designation for DYNE-101 in DM1 in May 2023. Key 2023 Milestones Dyne anticipates reporting initial data in the second half of 2023 from: the MAD placebo-controlled portion of the ACHIEVE trial of DYNE-101 in DM1 on safety, tolerability and splicing; and the MAD placebo-controlled portion of the DELIVER trial of DYNE-251 in DMD on safety, tolerability and dystrophin. Second Quarter 2023 Financial Results Cash position: Cash, cash equivalents and marketable securities were $207.7 million as of June 30, 2023, which is anticipated to fund operations through 2024. Research and development (R&D) expenses: R&D expenses were $59.1 million for the quarter ended June 30, 2023, compared to $46.7 million for the quarter ended June 30, 2022. General and administrative (G&A) expenses: G&A expenses were $7.6 million for the quarter ended June 30, 2023, compared to $6.1 million for the quarter ended June 30, 2022. Net loss: Net loss for the quarter ended June 30, 2023 was $64.9 million, or $1.08 per basic and diluted share. This compares with a net loss of $52.3 million, or $1.01 per basic and diluted share, for the quarter ended June 30, 2022. About Dyne Therapeutics Dyne Therapeutics is a clinical-stage muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases. With its proprietary FORCE™ platform, Dyne is developing modern oligonucleotide therapeutics that are designed to overcome limitations in delivery to muscle tissue. Dyne has a broad pipeline for serious muscle diseases, including clinical programs for myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) and a preclinical program for facioscapulohumeral muscular dystrophy (FSHD). For more information, please visit , and follow us on Twitter, LinkedIn and Facebook. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Dyne’s strategy, future operations, prospects and plans, objectives of management, the potential of the FORCE platform, the anticipated timelines for reporting data from the DYNE-251 and DYNE-101 clinical trials, the trial design of the DYNE-251 and DYNE-101 clinical trials, and the sufficiency of Dyne’s existing cash resources for the period anticipated, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “predict,” “project,” “potential,” “should,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Dyne may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; the timing of and Dyne’s ability to initiate and enroll patients in clinical trials; whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials; whether Dyne’s cash resources will be sufficient to fund the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; as well as the risks and uncertainties identified in Dyne’s filings with the Securities and Exchange Commission (SEC), including the Company’s most recent Form 10-Q and in subsequent filings Dyne may make with the SEC. In addition, the forward-looking statements included in this press release represent Dyne’s views as of the date of this press release. Dyne anticipates that subsequent events and developments will cause its views to change. However, while Dyne may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Dyne’s views as of any date subsequent to the date of this press release. Dyne Therapeutics, Inc. Condensed Consolidated Statement of Operations (Unaudited) (in thousands, except share and per share data) Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Operating expenses: Research and development $ 59,130 $ 46,664 $ 96,667 $ 74,899 General and administrative 7,606 6,091 15,533 13,638 Total operating expenses 66,736 52,755 112,200 88,537 Loss from operations (66,736 ) (52,755 ) (112,200 ) (88,537 ) Other (expense) income, net 1,834 451 3,111 650 Net loss $ (64,902 ) $ (52,304 ) $ (109,089 ) $ (87,887 ) Net loss per share—basic and diluted $ (1.08 ) $ (1.01 ) $ (1.88 ) $ (1.70 ) Weighted-average common shares outstanding used in net loss per share—basic and diluted 59,835,087 51,679,536 58,090,142 51,640,706 Dyne Therapeutics, Inc. Condensed Consolidated Balance Sheet Data (Unaudited) (in thousands) June 30, December 31, 2023 2022 Assets Cash, cash equivalents and marketable securities $ 207,733 $ 256,012 Other assets 43,688 50,313 Total assets $ 251,421 $ 306,325 Liabilities and Stockholders’ Equity Liabilities 44,544 53,961 Stockholders’ equity 206,877 252,364 Total liabilities and stockholders’ equity $ 251,421 $ 306,325 Contacts: Investors Amy Reilly areilly@dyne-tx.com 857-341-1203 Media Stacy Nartker snartker@dyne-tx.com 781-317-1938

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