- Initiating Registrational Cohorts with Update on Path to Registration by Year-End 2024 -
- Virtual Investor Event Today at 8:00 a.m. ET -
WALTHAM, Mass., Sept. 03, 2024 (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 new clinical data from its ongoing Phase 1/2 DELIVER trial of DYNE-251 in patients with Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping demonstrating unprecedented dystrophin expression and functional improvement in multiple cohorts.
"We believe these data reinforce the opportunity to transform the treatment paradigm for individuals living with Duchenne. In DELIVER, DYNE-251 achieved the highest level of dystrophin expression reported for an exon 51 skipping therapy and improvement in multiple functional endpoints across multiple cohorts that continued with time on therapy," said Wildon Farwell, M.D., MPH, chief medical officer of Dyne. "Our goal has always been to drive dystrophin levels that lead to functional benefit for patients – these data suggest that the distribution across cardiac, diaphragm and other skeletal muscles observed preclinically with the FORCE platform is translating in the clinic. Importantly, treatment with DYNE-251 resulted in meaningful improvements in SV95C, a digital outcome measure approved as a primary endpoint for Duchenne clinical trials in Europe. With these exciting data, we are moving quickly to initiate registrational cohorts in DELIVER, and we continue to pursue expedited approval pathways and plan to provide an update on our path to registration by the end of this year."
This assessment of the DELIVER trial evaluating DYNE-251 includes 6-month biomarker and functional data from 8 male patients enrolled in the 20 mg/kg (approximate PMO dose) cohort who were randomized to receive DYNE-251 or placebo once every four weeks, and 12-month functional data from 6 participants in the 10 mg/kg cohort.1 DYNE-251 demonstrated dose dependent exon skipping and dystrophin expression and improvement in multiple functional endpoints in both cohorts. Key findings include:
Dystrophin expression: DYNE-251 demonstrated unprecedented dystrophin expression as measured by Western blot. Patients treated with 20 mg/kg of DYNE-251 Q4W had a mean absolute dystrophin expression of 3.71% of normal (unadjusted for muscle content), more than 10-fold higher than the 0.3% reported in a clinical trial of the weekly standard of care, eteplirsen.2 When adjusting for muscle content, the DYNE-251 treated group reached 8.72% mean absolute dystrophin, which is greater than levels reported by peptide conjugate PMOs in clinical development.3
Function: Meaningful improvements in multiple functional endpoints were observed in both the 20 mg/kg and 10 mg/kg DYNE-251 Q4W groups, including North Star Ambulatory Assessment (NSAA), Stride Velocity 95th Centile (SV95C), 10-Meter Walk/Run Time (10-MWR), Time to Rise from Floor. The 10 mg/kg cohort showed continued improvement in all reported measures from 6 months to 12 months.1
Safety and Tolerability: Safety and tolerability data are based on 54 participants enrolled in the DELIVER trial. DYNE-251 demonstrated a favorable safety profile and the majority of treatment emergent adverse events were mild or moderate.4 No related serious treatment emergent adverse events have been identified other than in two participants at the 40 mg/kg dose level with events potentially related to study drug and both participants have recovered. Approximately 675 doses have been administered to date in the DELIVER trial, representing over 50 patient-years of follow-up.
Key Milestones for DELIVER and ACHIEVE Trials
Based on these data and regulatory interactions, Dyne is initiating registrational cohorts in the DELIVER trial and plans to provide an update on the path to registration by the end of 2024.
Dyne is also executing its ongoing Phase 1/2 ACHIEVE clinical trial of DYNE-101 in myotonic dystrophy type 1. The safety profile of DYNE-101 continues to be favorable and includes safety data up to the 6.8 mg/kg Q8W cohort.5 The company continues to engage with global regulators, including the U.S. Food and Drug Administration, and plans to provide an update on the path to registration for DYNE-101, including additional clinical data, by the end of 2024.
Virtual Investor Event
Dyne will host a video webcast event to discuss these DELIVER data today, September 3, 2024, at 8:00 a.m. ET and a replay will be accessible for 90 days following the presentation. An accompanying slide presentation for the event and an updated corporate presentation will also be available. To access these presentations and register for the live webcast and replay, please visit the Investors & Media section of Dyne's website at and the live event may also be accessed here.
About the DELIVER Trial
DELIVER is a Phase 1/2 global clinical trial evaluating DYNE-251, 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 enrolling ambulant and non-ambulant males with Duchenne muscular dystrophy (DMD) who are ages 4 to 16 and have mutations amenable to exon 51 skipping. 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. For more information on the DELIVER trial, visit (NCT05524883).
About DYNE-251
DYNE-251 is an investigational therapeutic being evaluated in the Phase 1/2 global DELIVER clinical trial for people living with DMD who are amenable to exon 51 skipping. DYNE-251 consists of a phosphorodiamidate morpholino oligomer (PMO) conjugated to a fragment antibody (Fab) that binds to the transferrin receptor 1 (TfR1) which is highly expressed on muscle. It is designed to enable targeted muscle tissue delivery and promote exon skipping in the nucleus, allowing muscle cells to create a truncated, functional dystrophin protein, with the goal of stopping or reversing disease progression. DYNE-251 has been granted fast track, orphan drug and rare pediatric disease designations by the U.S. Food and Drug Administration for the treatment of DMD mutations amenable to exon 51 skipping.
In addition to DYNE-251, Dyne is building a global DMD franchise and has preclinical programs targeting other exons, including 53, 45 and 44.
About Duchenne Muscular Dystrophy (DMD)
DMD is a rare disease caused by mutations in the gene that encodes for dystrophin, a protein critical for the normal function of muscle cells. These mutations, the majority of which are deletions, result in the lack of dystrophin protein and progressive loss of muscle function. DMD occurs primarily in males and affects an estimated 12,000 to 15,000 individuals in the U.S. and 25,000 in Europe. Loss of strength and function typically first appears in pre-school age boys and worsens as they age. As the disease progresses, the severity of damage to skeletal and cardiac muscle often results in patients experiencing total loss of ambulation by their early teenage years and includes worsening cardiac and respiratory symptoms and loss of upper body function by the later teens. There is no cure for DMD and currently approved therapies provide limited benefit.
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 X, LinkedIn and Facebook.
1. | During the OLE period, all participants in 10 mg/kg cohort were dose escalated to 20 mg/kg Q4W regimen. |
2. | No head-to-head trials have been conducted comparing DYNE-251 to eteplirsen. Eteplirsen data may not be directly comparable due to differences in trial protocols, dosing regimens and patient populations. Accordingly, these cross-trial comparisons may not be reliable. Eteplirsen data from J Neuromuscul Dis. 2021; 8(6): 989–1001. |
3. | No head-to-head trials have been conducted comparing DYNE-251 to SRP-5051. SRP-5051 data may not be directly comparable due to differences in trial protocols, dosing regimens, methodologies for calculating muscle content adjusted dystrophin and patient populations. Accordingly, these cross-trial comparisons may not be reliable. SRP-5051 data from Clinical Update: MOMENTUM (Study SRP-5051-201, Part B) Jan. 29, 2024. |
4. | DYNE-251 safety data as of August 21, 2024. |
5. | DYNE-101 safety data as of August 20, 2024. |
-啓動註冊群組，並在 2024 年年底之前更新註冊路徑-
-今天美國東部時間上午 8:00 的虛擬投資者活動-
馬薩諸塞州沃爾瑟姆，2024年9月3日（GLOBE NEWSWIRE）——專注於爲基因驅動疾病患者推進創新生命改變療法的臨床階段肌肉疾病公司達因療法公司（納斯達克股票代碼：DYN）今天公佈了其正在進行的針對可接受外顯子51的杜興肌肉萎縮症（DMD）患者的 DYNE-251 1/2 期交付試驗的新臨床數據跳過在多個隊列中表現出前所未有的肌營養不良蛋白表達和功能改善。
「我們認爲，這些數據增強了杜興氏患者改變治療模式的機會。在DELIVER中，DYNE-251 達到了外顯子51跳過療法報告的最高水平的肌萎縮蛋白表達，隨着治療時間的推移，多個隊列的多功能終點也有所改善。」 達因首席醫學官威爾登·法威爾萬德說。「我們的目標一直是提高肌營養不良蛋白水平，從而爲患者帶來功能益處——這些數據表明，臨床前使用FORCE平台觀察到的心臟、隔膜和其他骨骼肌的分佈正在臨床中得到轉化。重要的是，使用 DYNE-251 進行治療使 SV95C 有了顯著改善，這是一項數字結果衡量標準，被批准爲歐洲杜興臨床試驗的主要終點。有了這些令人興奮的數據，我們正在迅速着手啓動DELIVER的註冊群組，我們將繼續尋求加快的批准途徑，並計劃在今年年底之前提供註冊路徑的最新信息。」
對評估 DYNE-251 的 DELIVER 試驗的評估包括參加 20 mg/kg（大約 PMO 劑量）隊列的 8 名男性患者的 6 個月生物標誌物和功能數據，這些患者被隨機分配每四周接受一次 DYNE-251 或安慰劑，以及來自 10 mg/kg 隊列中 6 名參與者的 12 個月功能數據。1 DYNE-251 顯示了兩個隊列的劑量依賴性外顯子跳躍和肌萎縮蛋白的表達和多功能終點的改善。主要發現包括：
肌營養不良蛋白表達：根據西方印跡測量，DYNE-251 表現出前所未有的肌萎縮蛋白表達。服用 20 mg/kg DYNE-251 Q4W 治療的患者的平均絕對肌營養不良蛋白表達量爲正常水平的 3.71%（未調整肌肉含量），比每週護理標準臨床試驗中報告的 0.3% 高出 10 倍以上。2 調整肌肉含量時，DYNE-251 治療組的平均絕對肌營養不良蛋白達到 8.72%，高於肽偶聯物 pMOS 報告的水平正在臨床開發中。3
功能：在 20 mg/kg 和 10 mg/kg DYNE-251 Q4W 組中均觀察到多個功能終點的顯著改善，包括北極星動態評估 (NSAA)、步速第 95 厘位 (SV95C)、10 米步行/跑步時間 (10-MWR)、從地板上升的時間。10 mg/kg 隊列顯示所有報告的測量值持續改善，從 6 個月到 12 個月。1
安全性和耐受性：安全性和耐受性數據基於註冊參加DELIVER試驗的54名參與者。DYNE-251 顯示出良好的安全性，大多數治療緊急不良事件爲輕度或中度。4 除兩名受試者在 40 mg/kg 劑量水平下發生的事件可能與研究藥物有關外，未發現相關的嚴重治療緊急不良事件，且兩名參與者均已康復。迄今爲止，在DELIVER試驗中已經給藥了大約675劑，相當於患者50多年的隨訪。
交付和實現試驗的關鍵里程碑
基於這些數據和監管互動，達因正在啓動DELIVER試驗的註冊隊列，並計劃在2024年底之前提供註冊路徑的最新信息。
達因還正在進行的 DYNE-101 治療 1 型肌強直性營養不良症的 1/2 期 ACHIEVE 臨床試驗。DYNE-101 的安全狀況仍然良好，包括高達 6.8 mg/kg Q8W 隊列的安全數據。5 該公司繼續與包括美國食品藥品監督管理局在內的全球監管機構合作，並計劃在 2024 年底之前提供 DYNE-101 註冊路徑的最新信息，包括其他臨床數據。
虛擬投資者活動
達因將於今天，即美國東部時間2024年9月3日上午8點，舉辦一次網絡視頻直播活動，討論這些交付數據，並在演示結束後的90天內可以觀看重播。還將提供該活動的附帶幻燈片演示文稿和更新的公司演示文稿。要訪問這些演示文稿並註冊網絡直播和重播，請訪問達因網站的 「投資者與媒體」 部分，也可以在此處訪問直播活動。
關於 DELIVER 試用版
DELIVER 是一項評估 DYNE-251 的第 1/2 期全球臨床試驗，包括 24 周的多次遞增劑量 (MAD) 隨機安慰劑對照期、24 周的開放標籤延期和 96 周的長期延長。該試驗旨在進行註冊，正在招收年齡在4至16歲之間、具有可跳過外顯子51的突變的患有杜興氏肌肉萎縮症（DMD）的流動和非活動男性。主要終點是安全性、耐受性以及Western blot測得的肌營養素水平與基線的變化。次要終點包括肌肉功能、外顯子跳躍和藥代動力學的測量。有關 DELIVER 試用版的更多信息，請訪問 (NCT05524883)。
關於 DYNE-251
DYNE-251 是一種研究性治療藥物，目前正在進行第1/2期全球DELIVER臨床試驗的評估，該試驗針對的是願意接受外顯子51跳過的DMD患者。DYNE-251 由與片段抗體 (Fab) 偶聯的二酰亞磷酸鹽嗎啡低聚物 (PMO) 組成，該片段抗體結合在肌肉上高度表達的轉鐵蛋白受體 1 (TfR1)。它旨在實現靶向肌肉組織輸送並促進細胞核中的外顯子跳過，從而使肌肉細胞產生截斷的功能性肌萎縮蛋白蛋白，目的是阻止或逆轉疾病進展。DYNE-251 已被美國食品藥品監督管理局授予快速通道、孤兒藥和罕見兒科疾病認定，用於治療可跳過外顯子 51 的 DMD 突變。
除了 DYNE-251，達因還在建立全球DMD特許經營權，並有針對其他外顯子（包括53、45和44）的臨床前項目。
關於杜興氏肌肉萎縮症（DMD）
DMD 是一種罕見的疾病，由編碼肌萎縮素的基因突變引起，肌營養不良蛋白是一種對肌肉細胞正常功能至關重要的蛋白質。這些突變大部分是缺失，導致肌營養不良蛋白的缺乏和肌肉功能的逐漸喪失。DMD 主要發生在男性身上，在美國估計有 12,000 至 15,000 人受影響，在歐洲有 25,000 人受到影響。力量和功能喪失通常首先出現在學齡前男孩身上，並隨着年齡的增長而惡化。隨着疾病的發展，骨骼和心肌損傷的嚴重程度通常會導致患者在十幾歲時完全喪失活動能力，包括心臟和呼吸道症狀惡化以及青少年晚期上半身功能喪失。目前尚無治癒DMD的方法，目前批准的療法提供的益處有限。
關於達因療法
Dyne Therapeutics是一家處於臨床階段的肌肉疾病公司，致力於爲基因驅動疾病患者推出改變生活的創新療法。憑藉其專有的FORCE平台，達因正在開發現代寡核苷酸療法，這些療法旨在克服向肌肉組織輸送的侷限性。達因擁有廣泛的嚴重肌肉疾病治療渠道，包括1型肌強直性營養不良症（DM1）和杜興氏肌肉萎縮症（DMD）的臨床項目，以及面肩肱肌營養不良症（FSHD）的臨床前項目。欲了解更多信息，請訪問並在 X、領英和臉書上關注我們。
1。 | 在 OLE 期間，10 mg/kg 隊列中的所有參與者的劑量均增加到 20 mg/kg Q4W 方案。 |
2。 | 尚未進行過比較 DYNE-251 與 eteplirsen 的正面交鋒試驗。由於試驗方案、給藥方案和患者群體的差異，Eteplirsen的數據可能無法直接比較。因此，這些交叉試驗比較可能不可靠。Eteplirsen 數據來自 J Neuromuscul Dis. 2021；8 (6)：989—1001。 |
3. | 尚未進行過比較 DYNE-251 與 SRP-5051 的正面交鋒試驗。由於試驗方案、給藥方案、計算經調整的肌肉含量的方法和患者群體的差異，SRP-5051 數據可能無法直接比較。因此，這些交叉試驗比較可能不可靠。SRP-5051 數據來自《臨床更新：動量》（研究 SRP-5051-201，第 B 部分），2024 年 1 月 29 日。 |
4。 | 截至 2024 年 8 月 21 日的 DYNE-251 安全數據。 |
5。 | 截至 2024 年 8 月 20 日的 DYNE-101 安全數據。 |
