Sarepta Therapeutics Inc (SRPT) 2025 Q1 法說會逐字稿

Good afternoon, and welcome to the Sarepta Therapeutics first-quarter 2025 financial results conference call. As a reminder, today's program is being recorded.

下午好，歡迎參加 Sarepta Therapeutics 2025 年第一季財務業績電話會議。提醒一下，今天的節目正在錄製中。

At this time, I'll turn the call over to Mary Jenkins, Associate Director, Investor Relations. Please go ahead.

現在，我將把電話轉給投資者關係副總監瑪麗詹金斯 (Mary Jenkins)。請繼續。

Thank you, Martin, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the first quarter of 2025. The press release, slides and supplementary information are available on the Investor section of our website at sarepta.com, and our 10-Q was filed with the SEC this afternoon. Joining us on the call today are Doug Ingram, Ian Stepan, Dylan Murray and Dr. Louise Rodino-Klapac. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we will be making a number of forward-looking statements. Please refer to slide 2 on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta's control.

謝謝你，馬丁，也謝謝大家參加今天的電話會議。今天下午早些時候，我們發布了 2025 年第一季的財務表現。新聞稿、幻燈片和補充資訊可在我們網站 sarepta.com 的投資者部分找到，我們的 10-Q 已於今天下午向美國證券交易委員會 (SEC) 提交。今天參加電話會議的有 Doug Ingram、Ian Stepan、Dylan Murray 和 Louise Rodino-Klapac 博士。正式發言後，我們將開始問答環節。我想指出的是，在這次電話會議中，我們將做出一些前瞻性的陳述。請參閱網路廣播中的投影片 2，其中包含我們的前瞻性陳述。這些前瞻性陳述涉及風險和不確定性，其中許多超出了 Sarepta 的控制範圍。

Actual results could materially differ from these forward-looking statements, and any such risks can materially and adversely affect the business, the results of operations and trading prices for Sarepta's common stock.

實際結果可能與這些前瞻性陳述有重大差異，任何此類風險都可能對 Sarepta 普通股的業務、經營績效和交易價格產生重大不利影響。

For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent SEC filings. The company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today based on subsequent events or circumstances.

有關適用風險和不確定性的詳細描述，我們建議您查看該公司最新的 SEC 文件。該公司不承擔公開更新其前瞻性聲明的任何義務，包括基於後續事件或情況今天提供的任何財務預測。

As noted on slide 3, we will discuss non-GAAP financial measures on this webcast. Descriptions of these non-GAAP financial measures and reconciliations of GAAP to non-GAAP financial measures are included in today's press release and the slide presentation available in the Investors section of our website.

如投影片 3 所述，我們將在本次網路廣播中討論非 GAAP 財務指標。這些非公認會計準則 (non-GAAP) 財務指標的描述以及公認會計準則 (GAAP) 與非公認會計準則 (non-GAAP) 財務指標的對帳均包含在今天的新聞稿和我們網站「投資者」部分提供的幻燈片演示中。

And now I'll turn the call over to our President and CEO, Doug Ingram, who will provide an overview of our recent progress. Doug?

現在，我將把電話轉給我們的總裁兼執行長道格·英格拉姆 (Doug Ingram)，他將概述我們最近的進展。道格？

Thank you, Mary. Good afternoon, everyone, and thank you for joining Sarepta Therapeutics first-quarter 2025 financial results conference call. Across biotech and indeed the market more generally, the first quarter of 2025 has been a challenging one. Likewise, for Sarepta, we have faced challenges that have motivated us to take a more measured view for the remainder of 2025.

謝謝你，瑪麗。大家下午好，感謝您參加 Sarepta Therapeutics 2025 年第一季財務業績電話會議。對於生技領域乃至整個市場而言，2025 年第一季都是充滿挑戰的。同樣，對於 Sarepta 而言，我們面臨的挑戰促使我們對 2025 年剩餘時間採取更加審慎的看法。

Fortunately, Sarepta is in a better position than most of biotech today, as we have a significant number of approved therapies and significant revenue, a strong P&L and balance sheet and the ability to continue to independently drive our portfolio of gene therapies and siRNA programs. we are well positioned to weather this chaotic period.

幸運的是，Sarepta 目前的地位比大多數生物技術公司都要好，因為我們擁有大量獲批的療法和可觀的收入、強勁的損益表和資產負債表，並且有能力繼續獨立推動我們的基因療法和 siRNA 項目組合。我們已做好準備，度過這個混亂時期。

In the first quarter of 2025, we achieved $612 million in total net product revenue, representing 70% growth over the same quarter last year. Our PMO franchise grew 5%, achieving $237 million for the quarter and ELEVIDYS achieved sales of $375 million in the quarter representing a 180% increase over the same quarter last year. While our ELEVIDYS first quarter growth still represents the most successful in vivo gene therapy launch yet in history. In fact, in Q1, we treated more patients with gene therapy than ever before in the U.S. in a single quarter, we nevertheless fell short of expectations.

2025年第一季，我們的總淨產品收入達到6.12億美元，比去年同期成長70%。我們的 PMO 特許經營權成長了 5%，本季實現 2.37 億美元，ELEVIDYS 本季實現銷售額 3.75 億美元，比去年同期成長 180%。儘管我們的 ELEVIDYS 第一季的成長仍然代表著歷史上最成功的體內基因療法推出。事實上，在第一季度，我們在美國透過基因療法治療的患者數量超過了以往任何時期，儘管如此，我們仍未達到預期。

In a moment, Dallan will explain some of those quarterly factors including administrative issues, a severe flu season that resulted in delays in the effect of the recently reported safety event that motivated some families with scheduled infusions to pause for additional information.

稍後，達蘭將解釋一些季度因素，包括管理問題、嚴重的流感季節，這導致最近報告的安全事件的影響延遲，促使一些預定輸液的家庭暫停以獲取更多資訊。

Looking forward, we are changing our net product revenue guidance for the year to $2.3 billion to $2.6 billion across our 4 approved therapies. This change is driven by 3 factors: First, as you know, we recently reported that a boy infused with ELEVIDYS suffered an acute liver failure and passed away. This was an unimaginably tragic event for that family who with ELEVIDYS finally had reason to hope for a brighter future for their son. At Sarepta, we are deeply committed to the patients we serve. So this event, so markedly different than all other experience with ELEVIDYS was heartbreaking for all of us.

展望未來，我們將把今年的淨產品收入預期調整為 4 種核准療法的 23 億美元至 26 億美元。這項變更由三個因素推動：首先，如您所知，我們最近報導了一名註射了 ELEVIDYS 的男孩出現急性肝衰竭並去世。對這個家庭來說，這是一場難以想像的悲劇，有了 ELEVIDYS，他們終於有理由希望兒子有更光明的未來。在 Sarepta，我們全心為病人服務。因此，這次活動與 ELEVIDYS 的其他經歷截然不同，令我們所有人心碎。

While it is of no comfort to the family involved, it's important to remember that more than 800 patients have been infused with ELEVIDYS. The outcome of this event is inconsistent with all other experience with ELEVIDYS and we are continuing to explore what was uniquely different about this case than every of the other hundreds and hundreds of infusions that have occurred to date. What we do know is that while this young man's outcome was surprised, this did not represent a new safety signal for AAV-mediated gene therapy generally or ELEVIDYS more specifically nor did it change the positive risk benefit of ELEVIDYS, which has had a stable and laudable safety profile in the context of AAV-mediated gene therapy since first being infused back in January of 2018.

雖然這對受害者家屬來說並沒有什麼安慰，但重要的是要記住，已有超過 800 名患者註射了 ELEVIDYS。該事件的結果與 ELEVIDYS 的所有其他經驗不一致，我們正在繼續探索該案例與迄今為止發生的其他數百次輸液有何不同。我們所知道的是，雖然這位年輕人的結果令人驚訝，但這並不代表 AAV 介導的基因治療或更具體地說是 ELEVIDYS 的新安全信號，也沒有改變 ELEVIDYS 的積極風險效益，自 2018 年 1 月首次注入以來，ELEVIDYS 在 AAV 介導的基因治療中一直具有穩定且值得稱讚的安全性。

And of course, to support optimal outcomes, we have always prioritized patient safety. We have proactively placed significant monitoring requirements in our label. We require all sites to complete training before being permitted to treat and we have a never before seen or executed program, One called Sarepta Exchange that provides physicians with near real-time access to the most experienced and leading experts around the world so that outcomes are consistent across the country. We also provide education for our patient community, and we are committed to providing timely information about this life enhancing therapy.

當然，為了獲得最佳結果，我們始終將患者安全放在首位。我們已主動在標籤中提出重要的監控要求。我們要求所有站點在獲準治療之前完成培訓，並且我們有一個前所未見或執行過的項目，稱為 Sarepta Exchange，它為醫生提供與世界各地最有經驗和最頂尖的專家近乎實時的聯繫，以確保全國範圍內的結果一致。我們也為患者群體提供教育，並致力於及時提供有關這種改善生活的療法的資訊。

What we have observed is that top thought leaders who understand the data have not changed their treatment approach and informed families understand the positive risk benefit of ELEVIDYS. But there will be an impact on infusions as we roll out education in the broader physician community and families gain better insight into the profile of this disease-modifying therapy and have their questions answered.

我們觀察到，了解數據的頂尖思想領袖並沒有改變他們的治療方法，知情的家庭也了解 ELEVIDYS 的積極風險效益。但是，隨著我們在更廣泛的醫生群體中開展教育，並且家庭對這種改變疾病的療法的概況有更好的了解並且他們的問題得到解答，這將對輸液產生影響。

Second, as we have discussed, the administrative process from start form two infusion is particularly complicated for gene therapy. It includes, for instance, more appointments, more screenings and steps like single-case agreements, far more than other therapies. As we have launched the broader label and expanded the actual cadence from start form to infusion is taking about one month to six weeks longer than our original estimates, informing our forward forecasts. For the avoidance of doubt, this is not about ultimate access, but the administrative steps to get infused.

其次，正如我們所討論的，對於基因療法來說，從兩次輸注開始的管理過程特別複雜。例如，它包括更多的預約、更多的篩檢和單例協議等步驟，遠遠超過其他療法。由於我們推出了更廣泛的標籤並擴大了從開始形式到輸液的實際節奏，因此比我們最初的估計需要大約一個月到六週的時間，這為我們的未來預測提供了資訊。為避免疑問，這並不是關於最終的存取權限，而是關於注入的管理步驟。

As you know, we are quite proficient in working with sites to gain access. In fact, for our PMOs, our ultimate rate for gaining payer access has been well over 90%. And for ELEVIDYS, it currently remains at 100%, we are taking actions to shorten that turnaround time. There are some reasons to believe that our first quarter experience, which includes illness related delays and the typical first quarter insurance changes that can cause delays may have been longer than steady state. But for purposes of setting guidance for the year, we are assuming our first quarter experience on turnaround times is representative of the year as a whole. This will have a significant timing impact on infusion and hence a significant impact on revenue in 2025.

如您所知，我們非常擅長與網站合作以獲取存取權限。事實上，對於我們的 PMO 而言，最終獲得付款人存取權的比例已遠遠超過 90%。對於 ELEVIDYS 來說，目前仍維持 100%，我們正在採取措施縮短週轉時間。有理由相信，我們第一季的經歷（包括與疾病相關的延誤以及可能導致延誤的典型第一季保險變化）可能比穩定狀態更長。但為了製定年度指導，我們假設第一季的周轉時間經驗可以代表全年的情況。這將對輸液的時間產生重大影響，對 2025 年的收入產生重大影響。

Finally, three, the success we have seen with taught sites has caused an imbalance that we need to address across this year. 60% of our current revenue comes from top sites and top sites and top thought leaders. Their experience and enthusiasm for ELEVIDYS has resulted in many of them being fully booked out to 12 months. We need to direct much of our attention going forward to sites with more capacity. And we do not take lightly our decision to change guidance.

最後，第三，我們在教學站點上看到的成功導致了不平衡，我們需要在今年解決這個問題。我們目前 60% 的收入來自頂級網站和頂級思想領袖。他們對 ELEVIDYS 的經驗和熱情使得其中許多公司的預約在 12 個月內全部滿。我們需要將更多的注意力放在容量更大的站點上。我們不會輕易做出改變指導方針的決定。

But given the environment and some of the constraints we are working to address, we do believe it prudent. What we do know is this, ELEVIDYS is the first and only available disease-modifying therapy that offers the possibility of arresting further muscle damage in 80% or more of patients being daily damaged by Duchenne muscular dystrophy.

但考慮到環境和我們正在努力解決的一些限制，我們確實認為這是謹慎的。我們所知道的是，ELEVIDYS 是第一個也是唯一可用的疾病改良療法，它有可能阻止 80% 或更多每天受到杜氏肌肉營養不良症損害的患者進一步出現肌肉損傷。

It is a disease-modifying restore of significant amounts of a form of muscle protecting dystrophin and has observed over multiple studies, over 8 years of clinical experience and clinical evidence and in hundreds of patients of data, it is the only gene therapy proven to preserve function in boys dying from Duchenne. Without intervention every day, muscle of boys with Duchenne is destroyed and permanently replaced by fat and fibrotic tissue. With the FDA following the positive expert advisory panel and approving ELEVIDYS broadly for boys with Duchenne, families finally now have a chance to choose a different journey.

它是一種可以改變病情的療法，可以恢復大量保護肌肉的肌肉營養不良蛋白，並且經過多項研究、超過 8 年的臨床經驗和臨床證據以及數百名患者的數據觀察，它是唯一被證明可以保留杜氏肌肉營養不良症男孩功能的基因療法。如果不每天幹預，患有杜氏肌肉營養不良症的男孩的肌肉就會被破壞，並被脂肪和纖維化組織永久取代。隨著 FDA 聽取專家諮詢小組的積極意見並廣泛批准 ELEVIDYS 用於治療杜氏肌肉營養不良症男孩，家庭終於有機會選擇不同的治療方式。

Now that a disease-modifying therapy is finally available to them. If families are delayed in getting a therapy that can finally protect them from Duchenne's relentless damage and they are delayed either because of administrative issues or other delays or lack of information or even at times circulating misinformation, then we will have failed in our mission, and I hope we have proven repeatedly over these last 8 years, and we do not intend to fail in our mission. After our Chief Customer Officer, Dallan Murray, provides an overview, we will hear from our Head of R&D and Chief Scientific Officer, Dr. Louise Rodino-Klapac. She will speak to you about the continuing evolution of data for the impressive efficacy of ELEVIDYS and our plans to expand even further the population of patients who will have access to ELEVIDYS.

現在他們終於可以接受一種改善病情的療法了。如果家庭無法獲得最終能夠保護他們免受杜氏肌肉營養不良症無情損害的治療，而且這種治療要么是因為行政問題，要么是因為其他延誤，要么是因為缺乏信息，甚至有時是因為傳播錯誤信息，那麼我們的使命就失敗了，我希望我們在過去的 8 年裡已經反复證明了這一點，我們不想在我們的使命上失敗。在我們的首席客戶長 Dallan Murray 提供概述之後，我們將聽取我們的研發主管兼首席科學官 Louise Rodino-Klapac 博士的演講。她將向您介紹 ELEVIDYS 令人印象深刻的療效的數據的持續發展，以及我們進一步擴大可使用 ELEVIDYS 的患者群體的計劃。

Finally, Dr. Rodino-Klapac will provide an overview of the great progress we are making on our LGMD portfolio, and we'll discuss our progress with our siRNA platform, including our plan to share our proof of biology and proof of concept data from both our FSHD and DM1 programs in the second half of this year.

最後，Rodino-Klapac 博士將概述我們在 LGMD 產品組合上取得的巨大進展，並討論我們在 siRNA 平台上的進展，包括我們計劃在今年下半年分享來自 FSHD 和 DM1 專案的生物學驗證和概念驗證數據。

And with that, let me turn the call over to our Chief Customer Officer Dallan Murray. Dallan?

現在，請容許我將電話轉給我們的首席客戶長 Dallan Murray。達蘭？

Thank you, Doug, and good afternoon. My comments today are focused on three areas: context for what happened in Q1, how we plan to achieve our revised full-year guidance for 2025, and what gives us confidence in our ability to achieve that guidance.

謝謝你，道格，下午好。我今天的評論主要集中在三個方面：第一季發生的事情的背景、我們計劃如何實現修訂後的 2025 年全年指引，以及是什麼讓我們對實現該指引的能力充滿信心。

Regarding our Q1 performance, in addition to the safety event, there were two issues that impacted our results late into the quarter. Firstly, the severe flu season caused a number of patients to delay their infusion dates. Secondly, we faced administrative issues at some sites the most impactful of which was with Medical, California's Medicaid program that pushed out patients infusion dates. Importantly, these specific administrative challenges have now been successfully resolved.

關於我們第一季的業績，除了安全事件之外，還有兩個問題影響了我們本季末的業績。首先，嚴重的流感季節導致許多患者推遲了輸液日期。其次，我們在一些站點遇到了管理問題，其中影響最大的是醫療問題，加州的醫療補助計劃推遲了患者的輸液日期。重要的是，這些具體的管理挑戰現已成功解決。

Now I'll outline how our first quarter performance informed our revised guidance and the actions we'll take. First, the safety event led some patients and families scheduled for late March dosing to delay treatment while they saw out more information. We immediately initiated extensive outreach to our leading treaters in the broader community. Conversations have revealed that access to comprehensive safety data, including our Biomet marker safety data, which Louise will discuss in her prepared remarks, in conjunction with the 2-year EMBARK data provides the necessary context for health care providers and patients to move forward with confidence.

現在我將概述我們的第一季業績如何影響我們的修訂指導以及我們將採取的行動。首先，安全事件導致一些原定於 3 月底服藥的患者和家屬推遲治療，等待了解更多資訊。我們立即開始向更廣泛社區中的主要治療者進行廣泛的宣傳。對話表明，獲取全面的安全數據（包括我們的 Biomet 標記安全數據，Louise 將在她的準備好的發言中討論這些數據）與 2 年的 EMBARK 數據相結合，為醫療保健提供者和患者充滿信心地前進提供了必要的背景。

Our current focus is on disseminating this information across the wider treating and referring physician landscape, which is a process that takes time. As a result, we anticipate Q2 revenue could be as much as 20% lower than Q1.

我們目前的重點是向更廣泛的治療和轉診醫生傳播這些訊息，這是一個需要時間的過程。因此，我們預計第二季的營收可能會比第一季低 20%。

Looking ahead, we project a pickup in demand beginning in the summer and extending through the remainder of the year. Therefore, our long-term demand outlook for the therapy remains strong, and we expect only a temporary impact. Furthermore, we are encouraged that we continue to receive enrollment forms for both ambulant and non-ambulant patients. Secondly, as we discussed the administrative path for gene therapy from initial paperwork to infusion is inherently complex, involving significantly more appointments, tests and steps than typical therapies.

展望未來，我們預計需求將從夏季開始回升，並持續到今年剩餘時間。因此，我們對該療法的長期需求前景仍然強勁，我們預計只會產生暫時的影響。此外，我們很高興能夠繼續收到可行走和不可行走患者的報名表。其次，正如我們所討論的，基因療法從最初的文書工作到輸液的行政路徑本質上是複雜的，涉及的預約、測試和步驟比典型的治療要多得多。

However, with the broader label and our expansion to a wider range of patients, the actual start form 2 infusion cadence is extending by 1 to 1.5 months beyond initial estimates. This longer duration is primarily attributable to more rigorous screening protocols implemented to ensure patient safety within this expanded population, coupled with the intricate logistical requirements at the site level, including the navigation of single case agreements with payers.

然而，隨著標籤的擴大和我們向更廣泛患者的擴展，從 2 號表格開始的實際輸注節奏比最初的估計延長了 1 到 1.5 個月。持續時間較長的主要原因是實施了更嚴格的篩檢方案，以確保這一擴大的人群中的患者安全，再加上站點層面複雜的後勤要求，包括與付款人達成單例協議。

We are actively working with individual sites to create more efficiencies and less delay and have developed comprehensive tools for families to help navigate the journey. But while we are working to shorten turnaround times, we are nonetheless taking a conservative approach and incorporating the longer Q1 turnaround into our revised 2025 guidance.

我們正在積極與各個站點合作，以提高效率、減少延誤，並為家庭開發了全面的工具來幫助他們規劃旅程。不過，儘管我們正在努力縮短週轉時間，但我們仍然採取保守的方法，並將更長的第一季週轉時間納入我們修訂後的 2025 年指導方針中。

Thirdly, regarding site capacity. We observed a dichotomy across our network. While our total network capacity is robust, our most established and recognized treatment sites are facing substantial demand, resulting in appointment lead times approaching a year due to near full operational capacity. Simultaneously, a significant number of treatment centers across the country have the potential to increase their patient volume and contribute more significantly to our reach.

第三，關於場地容量。我們觀察到整個網路存在二分法。雖然我們的總網路容量強大，但我們最成熟和最受認可的治療站點面臨著巨大的需求，由於接近滿載的營運能力，導致預約時間接近一年。同時，全國各地的許多治療中心都有潛力增加患者數量，並對我們的服務範圍做出更大的貢獻。

Our strategy involves a proactive approach to engage these centers more deeply through enhanced high-touch support like we have done with the leading treatment centers. This focused effort bolstered by the encouraging two-year clinical data we highlighted earlier, is generating positive momentum in expanding our site engagement and our overall network utilization.

我們的策略是採取積極主動的方式，透過加強高接觸支持，更深入地與這些中心互動，就像我們對領先的治療中心所做的那樣。在我們先前強調的令人鼓舞的兩年臨床數據的支持下，這項重點努力正在為擴大我們的站點參與度和整體網路利用率產生積極勢頭。

Lastly, our teams are now intensifying their efforts to promote the deep and impressive evidence for the benefits of ELEVIDYS. We launched our comprehensive HCP and patient promotional campaign in the first quarter, which includes a fully built-out elevidys.com website and significant direct-to-consumer investment through digital channels designed to drive awareness and understanding.

最後，我們的團隊目前正在加強宣傳 ELEVIDYS 益處的深刻而令人印象深刻的證據。我們在第一季啟動了全面的 HCP 和患者推廣活動，其中包括全面構建的 elevidys.com 網站和透過數位管道進行的大量直接面向消費者的投資，旨在提高知名度和理解力。

With focused work already underway to address these three key areas: education, tightening turnaround times, and site capacity optimization, we have a clear path forward to effectively support the patient community and achieve our revised guidance. Taken together, we firmly believe that our collective efforts are guided by the critical principle that time is muscle and will ultimately result in more patients gaining access to our therapy faster. The fundamental size of the opportunity remains unchanged, and we are resolute in our intention to reach every eligible patient and continue to change the course of this devastating disease.

我們已開始集中精力解決以下三個關鍵領域：教育、縮短週轉時間和優化場地容量，我們有明確的前進方向，可以有效地支持患者群體並實現我們修訂後的指導方針。總之，我們堅信，我們的共同努力將遵循「時間就是力量」這一關鍵原則，最終將使更多患者更快獲得我們的治療。機會的根本規模保持不變，我們堅定地致力於幫助每一位符合條件的患者，並繼續改變這種毀滅性疾病的進程。

Thank you for your attention today. And with that, I would like to hand over the call to our Head of R&D and Chief Scientific Officer. Dr. Louise Rodino-Klapac. Louise?

感謝您今天的關注。說完這些，我想把電話交給我們的研發主管兼首席科學官。路易絲·羅迪諾-克拉帕克博士。路易絲？

Thank you, Dallan. The role of science in transforming patient lives has never been more important than it is at this moment. At Sarepta, science is foundational to who we are. I'll focus my comments today in three areas: ELEVIDYS, including additional data that supports safety and efficacy, the progress we've made in advancing our limb-girdle portfolio, solidifying our scientific leadership in neuromuscular diseases and the momentum behind our siRNA therapies, including the opportunity they hold to be best in class.

謝謝你，達蘭。科學在改變患者生活中的作用從未像現在這樣重要。在 Sarepta，科學是我們的基石。我今天的評論將集中在三個方面：ELEVIDYS，包括支持安全性和有效性的額外數據、我們在推進肢帶產品組合方面取得的進展、鞏固我們在神經肌肉疾病領域的科學領導地位以及我們的 siRNA 療法背後的發展勢頭，包括它們成為同類最佳療法的機會。

Further, we are excited to share the depth of our research at our upcoming R&D Day later this year. This work will fuel future innovations to treat diseases for which therapies are either nonexistent or inadequate. Beginning with ELEVIDYS, we provided data to the FDA, and we'll continue to work with them on any necessary updates to the ELEVIDYS label or monitoring requirements. Safety remains our top priority and as we have these past weeks beginning at MDA, we will continue to ensure that our community stakeholders are informed in a timely manner and that we address their questions.

此外，我們很高興在今年稍後即將舉行的研發日上分享我們研究的深度。這項工作將推動未來治療尚無治療方法或治療方法不充分的疾病的創新。從 ELEVIDYS 開始，我們就向 FDA 提供了數據，並且我們將繼續與他們合作，對 ELEVIDYS 標籤或監控要求進行任何必要的更新。安全仍然是我們的首要任務，正如我們過去幾週在 MDA 開始做的那樣，我們將繼續確保及時向社區利益相關者通報情況，並解決他們的問題。

Regarding safety, in patients treated with ELEVIDYS, we see no difference in the rates of adverse events and relationship to age or weight. Furthermore, no relationships have been identified between the liver safety biomarkers, bilirubin, GGT and INR and the total dose administered for patient age or patient weight. Shown on this slide are bilirubin values versus all cohorts in Study 103 and EMBARK. Regardless of whether it's change from baseline, absolute peak or peak value, there is no correlation with weight or age. The same holds true for cardiac safety biomarkers, including troponin.

關於安全性，在接受 ELEVIDYS 治療的患者中，我們發現不良事件發生率與年齡或體重的關係沒有差異。此外，尚未發現肝臟安全生物標記膽紅素、GGT 和 INR 與患者年齡或患者體重所施用的總劑量之間的關係。此投影片顯示的是研究 103 和 EMBARK 中所有隊列的膽紅素值。無論是相對於基線的變化、絕對峰值或峰值，都與體重或年齡沒有相關性。對於包括肌鈣蛋白在內的心臟安全生物標記也是如此。

The totality of our data in over 800 patients support safety of ELEVIDYS weight-based dosing across the label population of patients with Duchenne, regardless of ambulatory status. Life cycle development for ELEVIDYS continues to congress, highlighted by multiple activities.

我們從 800 多名患者身上收集到的全部數據都支持 ELEVIDYS 基於體重的給藥在杜氏肌肉營養不良症患者標籤人群中的安全性，無論其是否能夠活動。ELEVIDYS 的生命週期開發繼續進行，並以多項活動為亮點。

Starting with ENVISION, our post-marketing commitment trials for ELEVIDYS. ENVISION to Phase III global placebo-controlled trial in older ambulatory and non-ambulatory individuals with Duchenne and has progressed well. In the United States, enrollment is complete, and we continue to dose ex US. Our last patient last visit is expected in 2027 following an 18-month placebo-controlled period.

從 ENVISION 開始，我們對 ELEVIDYS 進行上市後承諾試驗。ENVISION 在患有杜氏肌肉營養不良症的老年可行走和不可行走患者中開展了 III 期全球安慰劑對照試驗，並取得了良好進展。在美國，招生工作已經完成，我們將繼續在美國以外地區進行招生工作。經過 18 個月的安慰劑對照期後，我們的最後一位患者預計將於 2027 年進行最後一次就診。

Next, for AAV-Rh74 antibody-positive patients, we are conducting two studies, Study 104 with imlifidase to cleave antibodies and study 105 to remove antibodies with plasmapheresis. We expect to have expression and safety data from both of these studies in the second half of 2025. We continue to advance our understanding of ELEVIDYS and publish and share these scientific data in support of the DMD population. The evidence continues to build supporting safety and efficacy of ELEVIDYS, particularly as time progresses as compared to the natural history.

接下來，針對AAV-Rh74抗體陽性患者，我們正在進行兩項研究，研究104使用imlifidase裂解抗體，研究105使用血漿置換去除抗體。我們預計將在 2025 年下半年獲得這兩項研究的表達和安全數據。我們不斷加深對 ELEVIDYS 的了解，並發布和分享這些科學數據以支持 DMD 族群。支持 ELEVIDYS 安全性和有效性的證據不斷增加，特別是隨著時間的推移與自然史相比。

In that spirit, we shared important updates at this year's NDA meeting, including results from our 2-year EMBARK and 3-year pooled analysis, indicating stabilization or slowing of disease progression compared with well-matched external control assessed by functional outcomes predictive for delaying loss of ambulation. At 2 years, EMBARK Part 1 ELEVIDYS-treated patients demonstrated statistically significant and clinically meaningful functional benefit in NSAA total score, time to rise and 10-meter walk run versus a propensity score weighted external control cohort.

本著這種精神，我們在今年的 NDA 會議上分享了重要的更新，包括我們 2 年 EMBARK 和 3 年匯總分析的結果，這些結果表明，與匹配良好的外部控制相比，疾病進展穩定或減緩，並通過預測延遲喪失行走能力的功能結果進行評估。兩年後，與傾向評分加權的外部對照組相比，EMBARK 第 1 部分 ELEVIDYS 治療的患者在 NSAA 總分、起身時間和 10 公尺步行跑步方面表現出統計學上顯著且具有臨床意義的功能益處。

In addition, and as previously mentioned on last quarter's call, the muscle MRI data we observed showed minimal progression in underlying muscle pathology in ELEVIDYS-treated patients, underscoring the importance of treating as soon as possible to preserve muscle. Lastly, we're looking forward to sharing additional data from the EMBARK study at this year's ASGCT's annual meeting this month in New Orleans, Louisiana.

此外，正如上個季度電話會議中提到的那樣，我們觀察到的肌肉 MRI 數據顯示，接受 ELEVIDYS 治療的患者的潛在肌肉病理進展很小，這強調了盡快治療以保留肌肉的重要性。最後，我們期待在本月於路易斯安那州新奧爾良舉行的 ASGCT 年會上分享 EMBARK 研究的更多數據。

Moving now to our program to limb-girdle muscular dystrophies, or LGMDs, each of the LGMD program builds on our experience with ELEVIDYS. We use the same vector, Rh-74, in both ELEVIDYS and our LGMD programs, which has a differentiated safety profile and high transduction efficiency. To this end, we've requested a platform technologies designation to enable leveraging of shared technology and future applications.

現在轉到我們的肢帶型肌肉營養不良症（LGMD）計劃，每個 LGMD 計劃都建立在我們與 ELEVIDYS 合作的經驗之上。我們在 ELEVIDYS 和 LGMD 程式中使用相同的載體 Rh-74，它具有差異化的安全性和高轉導效率。為此，我們請求指定平台技術，以便利用共享技術和未來的應用程式。

We were thrilled to announce in December 2024 that we completed enrollment and dosing from study SRP-9003 301 for emerging. Our Phase III clinical trial SRP-9003 to treat LGMD Type 2E or beta-sarcoglycanopathy. EMERGENE is a global study and the primary endpoint is biomarker expression of the beta-sarcoglycan protein. A pre-BLA meeting has occurred and the Office of Therapeutic products of OCP has confirmed eligibility for the accelerated approval pathway for this program.

我們很高興地在 2024 年 12 月宣布，我們已完成針對新興研究 SRP-9003 301 的招募和給藥。我們的 III 期臨床試驗 SRP-9003 用於治療 LGMD 2E 型或 β-肌聚醣症。EMERGENE 是一項全球性研究，主要終點是 β-肌聚醣蛋白的生物標記表達。已經召開了 BLA 前會議，並且 OCP 治療產品辦公室已確認該計劃符合加速審批途徑的資格。

Due to the similarities between ELEVIDYS and SRP-9003, we have agreement to leverage ELEVIDYS data and the SRP-9003 BLA. Director remains on track to submit a BLA to the FDA in the second half of 2025. We are also encouraged by the progress of our other LGMD programs. Just last month, we announced that we completed enrollment in dosing and study SRP-9004-102 or our DISCOVERY study.

由於 ELEVIDYS 和 SRP-9003 之間的相似性，我們同意利用 ELEVIDYS 資料和 SRP-9003 BLA。主任仍有望在 2025 年下半年向 FDA 提交 BLA。我們其他 LGMD 專案的進展也令我們感到鼓舞。就在上個月，我們宣布完成了劑量和研究 SRP-9004-102 或 DISCOVERY 研究的招募。

Discovery is a Phase I proof-of-concept study evaluating safety and expression of the alpha-sarcoglycan protein after treatment with SRP-9004. SRP-9004, is in development to treat LGMD type 2D or alpha-sarcoglycanopathy. We plan to initiate a Phase III trial before the end of the year.

Discovery 是一項 I 期概念驗證研究，旨在評估使用 SRP-9004 治療後 α-肌聚醣蛋白的安全性和表達。SRP-9004 正在開發中，用於治療 LGMD 2D 型或 α-肌聚醣症。我們計劃在今年年底前啟動第三階段試驗。

Also last month, we announced the following input from OTP, we were clear to proceed with study SRP-9005-101 for our COMPASS study in the United States. COMPASS is a first-in-human clinical study of SRP-9005, which is in the development for the treatment of LGMD type 2C or gamma sarcoglycanopathy.

同樣在上個月，我們宣布了來自 OTP 的以下意見，我們明確將繼續在美國進行 COMPASS 研究的 SRP-9005-101 研究。COMPASS 是 SRP-9005 的首次人體臨床研究，該研究正在開發用於治療 LGMD 2C 型或伽馬肌聚醣疾病。

As a reminder and with support from the agency, we adopted a Phase I/III seamless design clinical trial for SRP 9005, with the aim of facilitating a more efficient and faster path to BLA. We also look forward to highlighting our impressive pipeline and research at an upcoming R&D day in the latter half of 2025. As a preview, we have numerous programs in various stages of development across neuromuscular, central nervous system, cardiac and pulmonary indications. Many of these programs were nearing IND.

提醒一下，在該機構的支持下，我們採用了 SRP 9005 的 I/III 期無縫設計臨床試驗，目的是促進更有效率、更快速的 BLA 途徑。我們也期待在 2025 年下半年即將舉行的研發日上重點展示我們令人印象深刻的產品線和研究。作為預覽，我們有許多處於不同發展階段的項目，涉及神經肌肉、中樞神經系統、心臟和肺部適應症。許多此類項目都已接近 IND。

On the research side, we've continued to innovate across platforms, developing new AAV capsids as well as driving innovation in gene editing and enhanced delivery for RNA. The momentum around our other programs continues. We look forward to sharing data with you later this year around our FSHD 1 and DM1 programs. Beyond the multiple high-value catalysts to come this year and into the coming years, or siRNA programs leverage Sarepta's successful track record in developing and commercializing neuromuscular therapies, while also expanding our portfolio into CNS and pulmonary and broadening our focus into chronic therapies alongside onetime therapies.

在研究方面，我們不斷跨平台創新，開發新的 AAV 衣殼，並推動基因編輯和增強 RNA 傳遞的創新。我們其他項目的勢頭仍在持續。我們期待今年稍後與您分享有關我們的 FSHD 1 和 DM1 計劃的數據。除了今年和未來幾年的多種高價值催化劑之外，siRNA 計畫還利用 Sarepta 在開發和商業化神經肌肉療法方面的成功記錄，同時將我們的產品組合擴展到中樞神經系統和肺部，並將我們的重點擴大到慢性療法和一次性療法。

SRP 1001 is currently in clinical development to treat FSA Q1, and we are encouraged by the nonclinical data generated thus far. Cohort 2 in the SAD study is now fully enrolled, and we look forward to the data readout later this year.

SRP 1001 目前正處於治療 FSA Q1 的臨床開發階段，迄今為止產生的非臨床數據令我們感到鼓舞。SAD 研究的第 2 組目前已全部入組，我們期待今年稍後的數據讀數。

Turning to myotonic dystrophy type 1, or DM1, Cohort 1 in the SAD study is now fully enrolled, and we look forward to sharing the data from that study later in the year. Now to discuss our PMO platform. The ESSENCE trial, our post-marketing requirement for golodirsen and casimersen as well as mission for post-marketing commitment for EXONDYS are both fully enrolled and remain on track. We look forward to sharing data as soon as these studies are completed. And continue to collect and publish real-world data on the long-term effects of our PMO.

談到 1 型強直性肌肉營養不良症（DM1），SAD 研究中的第 1 組現已全部入組，我們期待在今年稍後分享該研究的數據。現在討論我們的 PMO 平台。ESSENCE 試驗、我們對 goldodirsen 和 casimersen 的上市後要求以及對 EXONDYS 的上市後承諾任務均已完全入組並保持正常進行。我們期待這些研究完成後立即分享數據。並繼續收集和發布有關我們的 PMO 長期影響的真實數據。

In closing, I'd like to take this opportunity to thank my Sarepta colleagues and those in the patient and clinical community. For those of us in the field of genetic medicine, the work continues and good science will always prevail. We must scrub the opportunities before us because patients are waiting.

最後，我想藉此機會感謝我的 Sarepta 同事以及患者和臨床界的各位同仁。對於我們這些從事基因醫學領域的人來說，這項工作將持續下去，好的科學將永遠盛行。我們必須放棄眼前的機會，因為病人正在等待。

I'll now turn the call over to Ian for an update on the financials. Ian?

我現在將電話轉給伊恩，以了解財務狀況的最新情況。伊恩？

Thanks, Louise, and good afternoon, everyone. This afternoon's financial results press release provided details for the first quarter of 2025 on a GAAP basis as well as a non-GAAP basis. Please refer to our press release available on Sarepta's website for a full reconciliation of GAAP to non-GAAP financial results. Beginning in the first quarter of 2025, the gains and losses on mark-to-market of strategic investments are excluded from our non-GAAP results.

謝謝，路易絲，大家午安。今天下午的財務業績新聞稿提供了 2025 年第一季的 GAAP 和非 GAAP 詳細資訊。請參閱 Sarepta 網站上的新聞稿，以了解 GAAP 與非 GAAP 財務結果的完整對照組。從 2025 年第一季開始，策略投資的以市價計價的損益將不計入我們的非公認會計準則績效。

For comparison purposes, non-GAAP financial results for the first quarter of 2024 have been updated to reflect this change. In Q1, we delivered strong year-over-year growth in revenue, continued disciplined approach to investment in R&D and SG&A and maintain our strong cash position with $647 million in cash, cash equivalents and investments and restricted cash as of the end of the quarter, and $600 million of additional liquidity available through our revolver.

為了進行比較，2024 年第一季的非 GAAP 財務結果已更新以反映此變更。在第一季度，我們的收入實現了強勁的同比增長，繼續嚴格控制對研發和銷售、一般及行政費用的投資，並保持了強勁的現金狀況，截至本季度末，我們的現金、現金等價物和投資以及受限現金為 6.47 億美元，並且通過我們的循環信貸工具還有 6 億美元的額外流動資金可用。

The decrease in our cash balance from last quarter was due to the funding of the Arrowhead collaboration upfront consideration of $825 million with cash on hand. Note, we have reported a Q1 GAAP and non-GAAP operating loss of $300 million and $250 million, respectively, both included a $584 million of R&D expense associated with our global licensing and collaboration and stock purchase agreement with Arrowhead.

我們的現金餘額較上一季有所減少，因為我們用現有現金支付了 Arrowhead 合作專案的 8.25 億美元預付款。請注意，我們報告的第一季 GAAP 和非 GAAP 營業虧損分別為 3 億美元和 2.5 億美元，其中包括與 Arrowhead 簽訂的全球許可和合作及股票購買協議相關的 5.84 億美元研發費用。

Excluding this transaction, we are reporting a GAAP and non-GAAP operating profit of $283 million and $334 million, respectively. In the first quarter, we delivered $612 million in total net product revenue, representing year-over-year growth of 70%. ELEVIDYS net product revenue was $375 million and grew 180% year over year and net product revenue from our PMO exon skipping franchise was $237 million, up 5% over the prior year.

不計入這筆交易，我們報告的 GAAP 和非 GAAP 營業利潤分別為 2.83 億美元和 3.34 億美元。第一季度，我們的產品淨總收入達到 6.12 億美元，年增 70%。ELEVIDYS 淨產品收入為 3.75 億美元，年增 180%，來自 PMO 外顯子跳躍特許經營的淨產品收入為 2.37 億美元，比上年增長 5%。

In Q1, we recognized $133 million of collaboration and other revenues. This primarily reflects $112 million of collaboration revenues related to Roche expired options of a certain program as well as $17 million of contract manufacturing revenues for sales of commercial ELEVIDYS supply to Roche. The reimbursable co-development costs under the Roche agreement, which is recorded at the contra operating expense totaled $29 million in Q1 compared to $22 million for the same prior year period.

第一季度，我們確認了 1.33 億美元的合作和其他收入。這主要反映了與羅氏某項目到期選擇權相關的 1.12 億美元合作收入，以及向羅氏銷售商業 ELEVIDYS 供應的 1,700 萬美元合約製造收入。根據羅氏協議，可報銷的共同開發成本（記錄在銷經營費用中）在第一季總計 2,900 萬美元，而去年同期為 2,200 萬美元。

Total revenues were $745 million in the first quarter and increased $331 million or 80% year over year. Q1 cost of sales totaled $138 million compared to $51 million in the same period of '24. The increase was driven by an increase in ELEVIDYS sales as well as an increase in cost of sales related to products sold to Roche.

第一季總營收為 7.45 億美元，年增 3.31 億美元，增幅為 80%。第一季銷售成本總計 1.38 億美元，而 24 年同期為 5,100 萬美元。成長的原因是 ELEVIDYS 銷售額的成長以及向羅氏銷售產品相關銷售成本的增加。

Now moving to our R&D expenses. On a GAAP basis, we recorded $773 million and $200 million in R&D expenses for the first quarter of 2025 and 2024, respectively, a year-over-year increase of $573 million. The increase is primarily due to the $584 million upfront and milestone expenses associated with aforementioned Arrowhead collaboration. On a non-GAAP basis, R&D expenses were $749 million for the first quarter of 2025 compared to $178 million for the same period of 2024, an increase of $571 million.

現在談談我們的研發費用。依照 GAAP 標準，我們在 2025 年第一季和 2024 年第一季的研發費用分別為 7.73 億美元和 2 億美元，年增 5.73 億美元。這一增長主要歸因於與上述 Arrowhead 合作相關的 5.84 億美元前期費用和里程碑費用。以非公認會計準則計算，2025 年第一季的研發費用為 7.49 億美元，而 2024 年同期為 1.78 億美元，增加了 5.71 億美元。

Now turning to SG&A. On a GAAP basis, SG&A totaled $134 million, up 5% year over year. This increase was primarily driven by an increase in compensation and other personnel expenses and higher sales and marketing spending to commercialize ELEVIDYS. On a non-GAAP basis, SG&A expenses totaled $107 million, up 7% year over year.

現在談談銷售、一般及行政費用 (SG&A)。根據 GAAP 標準，銷售、一般及行政費用總計 1.34 億美元，較去年同期成長 5%。這一增長主要得益於薪酬和其他人員費用的增加，以及為實現 ELEVIDYS 商業化而增加的銷售和行銷支出。以非公認會計準則計算，銷售、一般及行政費用總計 1.07 億美元，較去年同期成長 7%。

On a GAAP basis, we recorded an $83 million charge in other expense net in Q1 '25. This was primarily due to the loss on strategic investments, which includes a recurring fair value adjustments of investments of publicly traded companies, including Arrowhead. GAAP income taxes were $64 million in the quarter compared to $5 million in the prior year.

以 GAAP 計算，我們在 2025 年第一季的其他費用淨額中記錄了 8,300 萬美元。這主要是由於策略性投資的損失，其中包括對 Arrowhead 等上市公司投資的經常性公允價值調整。本季 GAAP 所得稅為 6,400 萬美元，去年同期為 500 萬美元。

The increase is driven primarily by increased taxable profit, largely due to ELEVIDYS revenues. Also on a GAAP basis, we reported a net loss of $448 million or $4.60 per basic and diluted share for the first quarter of 2025. We reported a non-GAAP net loss of $332 million or $3.42 per diluted share.

成長的主要原因是應稅利潤的增加，這主要歸功於 ELEVIDYS 的收入。此外，以 GAAP 計算，我們報告 2025 年第一季淨虧損 4.48 億美元，即每股基本虧損和稀釋虧損 4.60 美元。我們報告的非公認會計準則淨虧損為 3.32 億美元，即每股稀釋虧損 3.42 美元。

Now turning to our outlook for 2025. As mentioned earlier, we are revising our total product revenue guidance to $2.3 billion to $2.6 billion. This still represents a 37% increase from our 2024 total product revenue at the midpoint. Our PMO guidance remains the same at around $900 million. Our combined 2025 non-GAAP R&D and SG&A expenses, excluding the impact of the Arrowhead collaboration upfront transaction expense and potential DM1 development milestones, remains at $1.2 billion to $1.3 billion.

現在來展望一下 2025 年。如前所述，我們將總產品收入預期修改為 23 億美元至 26 億美元。這仍然比我們 2024 年中期的總產品收入成長了 37%。我們的 PMO 指導金額保持不變，約為 9 億美元。不包括 Arrowhead 合作前期交易費用和潛在 DM1 開發里程碑的影響，我們的 2025 年非 GAAP 研發和銷售、一般及行政費用總額仍為 12 億美元至 13 億美元。

However, we anticipate to be at the closer to the low end of the range.

然而，我們預計該數字將更接近該範圍的低端。

With our undrawn $600 million revolving credit facility, we are in a strong position to further invest in internal and external innovation and to support our capital allocation strategy. We believe our recent share price levels do not reflect the current value of the company today nor the growth potential we expect to achieve in the future. As such, we remain opportunistic and disciplined within our capital allocation strategy to deliver value to our shareholders while also preserving financial flexibility to invest in our long-term growth opportunities.

憑藉我們尚未提取的 6 億美元循環信貸額度，我們有能力進一步投資於內部和外部創新並支持我們的資本配置策略。我們認為，我們最近的股價水準既不能反映公司當前的價值，也不能反映我們預期未來實現的成長潛力。因此，我們在資本配置策略中保持機會主義和紀律性，為股東創造價值，同時保持財務靈活性，以投資我們的長期成長機會。

We remain well positioned for the future with four approved therapies, generating significant revenue and revenue growth, and we remain committed to sustained profit, operating expense leverage and positive cash flow for the remainder of the year.

我們擁有四種核准的療法，為未來做好了準備，創造了可觀的收入和收入成長，並且我們將繼續致力於在今年剩餘時間內保持持續的利潤、營運費用槓桿和正現金流。

And with that, I'll turn the call over to Doug to start the Q&A. Doug?

接下來，我會把電話轉給 Doug 開始問答環節。道格？

Thank you very much, Ian. Marvin, let's open the lines for Q&A.

非常感謝，伊恩。馬文，我們開始問答環節。

(Operator Instructions) Tazeen Ahmad, Bank of America Securities.

（操作員指示） Tazeen Ahmad，美國銀行證券。

Doug, I just wanted to ask you, on those three factors that you mentioned right at the beginning of the call, the capacity issues, the administrative processes that you mentioned and the results of the patient leaving families to have questions, which one, if any, has been the biggest driver of potential downside pressure leading you to revised guidance? And then as 2Q has progressed, have any of those I guess, gotten worse because you're talking about 20% lower sales relative to 1Q and we're still pretty, I guess, relatively early into the quarter.

道格，我只是想問您，在電話會議開始時您提到的三個因素，即容量問題、您提到的管理流程以及患者家屬提出疑問的結果，哪一個因素（如果有的話）是導致您修改指導意見的潛在下行壓力的最大驅動因素？然後，隨著第二季度的進展，我猜這些情況是否會變得更糟，因為你所說的銷售額相對於第一季度下降了 20%，而且我猜我們還處於本季度的初期。

Thank you for your question. So first, on the balance, it is a mix of all three. I think the cycle times is probably the one that mechanically affects forward guidance the most. But there's a bit of a mix there. What we're seeing going forward is that not a worsening.

感謝您的提問。因此，首先，從總體上看，它是三者的混合。我認為週期時間可能是對前瞻性指引影響最大的因素。但那裡有一點混亂。我們看到的情況並不是惡化。

In fact, again, we don't have enough data on the cycle time issue to suggest that we're being overly conservative. But we're at a minimum confident that we've hit steady state.

事實上，我們沒有足夠的關於週期時間問題的數據來表明我們過於保守。但我們至少有信心已經達到穩定狀態。

There's some reason to believe it might be a bit conservative. I mentioned earlier in the call, the first quarter had the most severe flu season, I think, in 15 years, and that caused some delays. There's the typical insurance changes that occur in the first quarter of every year. That causes some delays. There's a thesis that may be embedded in this four to six weeks additional cycle time might be some of that -- those particular first quarter issues.

有理由相信它可能有點保守。我之前在電話會議中提到，第一季是 15 年來最嚴重的流感季節，這造成了一些延誤。每年第一季都會發生典型的保險變動。這會導致一些延誤。有一種觀點認為，這四到六週的額外週期時間可能就是其中的一部分——那些特定的第一季問題。

But I think for planning purposes, we're assuming and I certainly think you should also assume that we're at steady state for the year. We have a lot of work to do, we're trying to do even more efficiently, but I don't think we should assume that we will.

但我認為，出於規劃目的，我們假設，我當然認為你也應該假設我們今年處於穩定狀態。我們有很多工作要做，我們正在努力做得更有效率，但我認為我們不應該想當然地認為我們會做到。

On the safety event, the issue, of course, to remember is that in the when the safety event occurred, it was right before March. So right the last month of the quarter. So of course, those who needed additional information, we're going to have delays and that is going to flow through into the second quarter as well. So it shouldn't be at all surprising that the second quarter would be soft as a result of that and so we're, of course, we're seeing that. And that's going to take some time.

關於安全事件，當然要記住的問題是，安全事件發生時正值三月之前。所以這是本季的最後一個月。因此，當然，對於需要更多資訊的人來說，我們將會遇到延遲，這也將延續到第二季​​。因此，第二季的銷售疲軟也就不足為奇了，當然，我們也看到了這一點。這需要一些時間。

We need to get out there. We need to get to the broader community. As I've mentioned before, in my prepared remarks, when we get to folks when the top thought leaders, which we were able to see right at the MDA conference when this all came out, it was quite clear that they were, to a person, at least from my interactions with them didn't see this as changing their prescribing behavior at all.

我們需要走出去。我們需要接觸更廣泛的社區。正如我之前在準備好的發言中提到的，當我們與頂尖思想領袖交談時，當這一切發生時，我們在 MDA 會議上就能夠看到，很明顯，至少從我與他們的互動來看，他們根本不認為這會改變他們的處方行為。

And we get the same answer when we talk to families, we just need to get out to more and more families. If you wanted to say what are the signals kind of as we sit here today, the signals are, I guess, what you would call the green shoots because we are seeing start forms are coming in. I can't give you a split right now, but start forms are coming in, both for ambulatory and non-ambulatory right now. So I think we are seeing the -- as we communicate and as we talk and as we educate, we're seeing that occur.

當我們與家庭交談時，我們得到了同樣的答案，我們只需要接觸越來越多的家庭。如果您想說我們今天坐在這裡時出現了哪些訊號，我想這些訊號就是您所說的綠芽，因為我們看到了萌芽形態的出現。我現在無法為您提供分組，但是現在開始表格已經到了，包括可行走的和不可行走的。所以我認為我們看到了——當我們交流、當我們交談、當我們教育時，我們看到了這種情況的發生。

And over time, there should be no difference in the reaction to this depending on whether you're ambulatory or non-ambulatory because as you saw and as Dr. Louise Rodino-Klapac showed you, in fact, the data is quite clear that there's a minority of patients that get liver enzymes, it doesn't occur in any greater amount or any more severity either on liver enzymes or bilirubin on non-ambulatory versus ambulatory patients.

隨著時間的推移，無論您是否能夠走動，對此的反應應該不會有差異，因為正如您所看到的以及 Louise Rodino-Klapac 博士向您展示的那樣，事實上，數據很清楚地表明，只有少數患者會出現肝酶，無論是肝酶還是膽紅素，在非走動患者和走動患者中都不會出現更大的程度或更嚴重的情況。

So I would say, we're seeing positivity when we actually get out there and we educate. And we've got a lot of work to do over the course of this year to get to those -- the secondary sites, where there is capacity one of our -- when I said earlier, one of our significant issues is we've been very, very successful with the big thought leaders, but those sites are often fully booked. So we really need to get to other sites and make sure that we are getting people to sites that have capacity, and we need to get more education out there, both to those physicians and to the broader family community, and then we'll continue to work on, on cycle times.

所以我想說，當我們真正走出去並進行教育時，我們看到了積極的影響。今年我們還有很多工作要做，才能到達那些二級場地，那裡有我們的一個容量——我之前說過，我們面臨的一個重大問題是，我們在與大思想領袖的合作中非常非常成功，但那些場地經常都被預訂滿了。因此，我們確實需要去其他站點，並確保我們將人們帶到具有容量的站點，並且我們需要在那裡對那些醫生和更廣泛的家庭社區進行更多的教育，然後我們將繼續努力，確定週期時間。

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

Doug, I want to follow up on that last phrase that you mentioned, how do you direct patients to those sites with more capacity? Are we talking like more community sites and why aren't these sites sort of at capacity like the main centers? Is it a staffing issue? Is it a demand issue? How do you plan on doing that? And is this the point where you think about opening more sites?

道格，我想跟進一下您提到的最後一句話，您如何將患者引導到那些容量更大的站點？我們談論的是更多的社區站點嗎？為什麼這些站點的容量不如主要中心？這是人員配置問題嗎？這是需求問題嗎？你打算怎麼做？您是否因此考慮開設更多站點？

I don't think as we sit here today that it's a number of sites issue. I think it's a focus issue. So really, the issue is -- and it should be of no surprise when you first launched a therapy, we really prioritize the big sites with the real thought leaders with a lot of experience and a lot of start forms, and we've spent a lot of time there. We've spent obviously, time on other sites, and they're all well trained, but we have spent as much time there with a lot of the good educational work that we need to do, including responding to this most recent safety event, but even beyond that, and frankly, in a more positive note, really getting out and talking about the brilliant data that came out on the crossover. Remember, that data is just lights out.

我認為，就我們今天坐在這裡的情況而言，這不是網站數量的問題。我認為這是一個焦點問題。所以，真正的問題是——當你第一次推出一種療法時，這應該不足為奇，我們確實優先考慮擁有真正思想領袖、經驗豐富、有很多起始形式的大型網站，並且我們在那裡花費了大量時間。顯然，我們已經在其他站點花費了時間，並且他們都接受了良好的培訓，但是，我們也在那裡花費了同樣多的時間，開展了我們需要做的大量良好教育工作，包括應對最近的安全事件，但除此之外，坦率地說，以更積極的態度，真正走出去，談論交叉中出現的出色數據。請記住，數據只是熄滅而已。

I mean it's -- kids on the therapy for two years were statistically significantly better than natural history on every single functional even at the one-year mark, when you get to the older ages because, of course, the kids dosed in the second phase of the trial, we're older now. Now they're in the decline phase, which is one of the problems with our original study as it relates to NSA. They are significant statistically on every measure, including NSA. And then you saw the trajectory analysis.

我的意思是，接受兩年治療的孩子在每項功能上都比自然史表現好得多，即使在一年後，當你年齡較大時也是如此，因為當然，在試驗的第二階段接受治療的孩子現在年齡較大了。現在他們正處於衰退階段，這是我們最初的研究中與 NSA 相關的問題之一。它們對包括 NSA 在內的每項措施都具有統計意義。然後你就看到了軌跡分析。

And then you saw the muscle MRI, do you want to linger on that muscle MRI. That's a really powerful thing. I think there was probably a moment when some of us wondered whether you would actually be able to see in one year a really significant difference in muscle quality, what you do across a significant number of muscles you see this very different result where kids that have been dosed with ELEVIDYS have their muscle preserved and much less fat in fibrotic tissue and kids that didn't get dosed a year later or missing a lot of that muscle and have a lot of infiltration of fat and fibrotic tissue. We see to get all of that information and have those conversations with those secondary sites.

然後你看到了肌肉 MRI，你想在那塊肌肉 MRI 停留片刻嗎？這確實是一件很強大的事。我想我們中的一些人可能曾經想過，一年之內是否真的能看到肌肉質量有顯著的差異，如果對大量肌肉進行觀察，就會看到截然不同的結果：服用過 ELEVIDYS 的孩子的肌肉得到了保留，纖維化組織中的脂肪少了很多，而一年後沒有服用 ELEVIDYS 的孩子或缺少了很多肌肉，並且有大量脂肪和纖維化組織浸潤了很多。我們希望獲得所有這些資訊並與這些二級網站進行對話。

What we can't do in any real way or in a thoughtful way to sort of redirect people's start forms from 1 site to another. That's really not possible. What we can do is really spend a lot of time with them, spend a lot of energy with them and spend a lot of education with them as well as making sure that we're educating the patient community across the United States. And I think it is going to create significant dividends, both I think for us and our revenue, but far more important than that, getting kids infused that are going to benefit from this life-changing therapy. Thank you for your questions, Ritu.

我們無法以任何實際或周到的方式將人們的開始表單從一個網站重定向到另一個網站。這實在不可能。我們能做的就是花很多時間與他們在一起，花很多精力，花很多時間對他們進行教育，並確保我們正在教育全美各地的患者群體。我認為這將為我們自己和我們的收入帶來豐厚的回報，但更重要的是，讓接受這種改變生命的療法治療的孩子們受益。謝謝你的提問，Ritu。

Louise Chen, Scotiabank.

加拿大豐業銀行的 Louise Chen。

I wanted to ask you, of the new guidance you gave, what percent of sales does ELEVIDYS represent? And also, are you planning or expecting that sales will recover starting in the third quarter?

我想問一下，在您給出的新指導中，ELEVIDYS 佔銷售額的百分之多少？另外，您是否計劃或預計銷售額將從第三季開始復甦？

So the -- 2 answers to that. Obviously, we're pulling our guidance down primarily -- well, exclusively really from ELEVIDYS. So you can do the math on that. This is an ELEVIDYS related issue. And then yes, we are assuming starting in the summertime and starting really in the second half of the year that we're going to see a significant uptick.

所以——這個問題有兩個答案。顯然，我們下調預期主要是因為——嗯，實際上完全是因為 ELEVIDYS。所以你可以對此進行計算。這是一個與 ELEVIDYS 相關的問題。是的，我們假設從夏季開始，實際上從下半年開始，我們將看到顯著的上升。

We're already seeing, again, using a (inaudible) phrase, the green shoots of that. But what we really do know when we've talked to a lot of physicians is there are a lot of families that prioritize the summer program.

再次使用（聽不清楚）短語，我們已經看到了它的萌芽。但是，當我們與許多醫生交談時，我們確實知道有很多家庭優先考慮夏季計劃。

There's a lot of monitoring that goes on with this therapy. lot of times, people have to travel with this therapy. There are other family members and brothers and sisters to be considered. And so we really are expecting and we believe we're going to see a significant uptick starting in the summertime plus the back half of the year as we execute. And we will execute.

這種療法需要進行大量的監測。很多時候，人們都必須帶著這種療法去旅行。還有其他家庭成員和兄弟姊妹需要考慮。因此，我們確實期待並相信，隨著我們實施，我們將從夏季以及今年下半年看到顯著的上升。我們將執行。

Yes. Very specifically, we gave guidance of $900 million for our PMO. We maintained the guidance of $900 million from our PMO franchise. So the revision in our total net product revenue was all related to level.

是的。具體來說，我們為 PMO 提供了 9 億美元的指導金額。我們維持 PMO 特許經營權 9 億美元的指導金額。因此，我們總淨產品收入的修訂都與水準有關。

Andrew Tsai, Jefferies.

安德魯·蔡（Andrew Tsai），傑富瑞（Jefferies）。

My question is around this -- following this patient death. Some investors are wondering about a worst-case scenario where ELEVIDYS is pulled from the market, something more drastic basically than what your revised guidance assumes. The appointment. And the appointment of Dr. Prasad today might not help with that narrative.

我的問題與此有關──關於這個病人的死亡。一些投資者擔心最壞的情況是 ELEVIDYS 退出市場，這比您修訂後的指導意見所假設的更為激烈。任命。今天對普拉薩德博士的任命可能對這種說法沒有幫助。

So can you walk us through how you think about that potential risk, especially since you do have an accelerated approval in the non-ambulatory DMD.

那麼，您能否向我們介紹一下您對這種潛在風險的看法，特別是因為您在非步行性 DMD 方面確實獲得了加速批准。

Sure, sure. First, on the appointment, I want to be clear, I'm not going to obviously comment on any particular appointment, which we just got news of today. What I do remain confident about is that the FDA is going to be the FDA that it's been for the last 100 years, which is an organization dedicated to following great science and fulfilling its mission of bringing life-enhancing therapies that are safe and efficacious to patients. And there's no reason to believe that, that should change or that anyone would permit that to change. I would remind you as it relates to ELEVIDYS, the evidence for its approval was brilliant at the time absolutely remarkable and then only got more impressive over time following a positive Advisory Committee meeting.

當然，當然。首先，關於任命，我想明確一點，我不會對任何特定的任命發表評論，我們今天才得到消息。我確信的是，FDA 將會一如既往地保持百年傳統，是一個致力於追尋偉大科學、履行使命的組織，即為患者帶來安全有效的改善生活的療法。並且沒有理由相信這種情況應該改變或任何人會允許這種情況改變。我想提醒你，就 ELEVIDYS 而言，其批准的證據在當時非常出色，絕對引人注目，而且在一次積極的諮詢委員會會議之後，隨著時間的推移，它變得更加令人印象深刻。

We got the original approval. The totality of evidence was clear that we were changing the trajectory of this disease. And then thereafter, we have the crossover data that we unblinded all prespecified every functional measure was strongly statistically positive, the muscle MRI is brilliant. There's no doubt that this therapy is changing the lives of patients. There is no reason to believe that this safety event would be the motivator as an example for something drastic with this therapy.

我們獲得了原始批准。全部證據都清楚地表明，我們正在改變這種疾病的發展軌跡。此後，我們得到了交叉數據，我們揭開了所有預先指定的功能測量的神秘面紗，這些數據在統計上都是非常積極的，肌肉 MRI 非常出色。毫無疑問，這種療法正在改變患者的生活。沒有理由相信這一安全事件會成為採取此類療法的重大舉措的先例。

I would remind you that ELEVIDYS has 1 of the most impressive safety profiles in the context of AAV-mediated gene therapy that has ever existed. It is true that every AAV-mediated gene therapy comes with a risk of elevated liver enzymes. And in other cases, there have been significant consequences for that. They are rare. With respect to us, they are particularly rare.

我要提醒您，ELEVIDYS 在 AAV 介導的基因療法領域中擁有最令人印象深刻的安全性之一。確實，每種 AAV 介導的基因療法都存在肝臟酵素升高的風險。在其他情況下，這會產生嚴重後果。它們很稀有。對我們來說，它們尤其罕見。

In fact, this 1 incident is unique, not only in its outcome, but even in the sort of the course of it.

事實上，這事件是獨一無二的，不僅其結果如此，甚至其過程也是如此。

There's something very different about it. And it's in the context of AAV-mediated gene therapy. It's in the context of the understanding that there is always a risk of elevated liver enzymes in the vast majority of cases. And with this 1 case being the only exception, they respond very rapidly to a modest increase in steroids and come back down to baseline. So -- there is no reason to believe that a science-driven organization and science minded regulators would be considering anything other than the fact that they should be proud that they approve this brilliant therapy.

它有一些非常不同的東西。這是在 AAV 介導的基因治療背景下的。這是基於這樣的認知：在絕大多數情況下，肝酵素升高的風險始終存在。除此 1 個案例外，他們對類固醇的適度增加反應非常迅速，並恢復到基線水平。因此——沒有理由相信，一個以科學為導向的組織和具有科學意識的監管者會考慮除了他們應該為批准這種出色的療法而感到自豪之外的任何事情。

Eliana Merle, UBS.

瑞銀的 Eliana Merle。

Just in terms of a potential label update for ELEVIDYS, can you talk us through your latest expectations there for any potential update or conversations with the FDA after the patient death. I guess when could we potentially hear about a label update and what your expectations are for what this could look like?

就 ELEVIDYS 的潛在標籤更新而言，您能否向我們介紹您對患者死亡後任何潛在更新或與 FDA 對話的最新期望。我想我們什麼時候可以聽到有關標籤更新的消息以及您對此有何期望？

And then just in terms of the commercial uptake, you mentioned that there were some patients who were scheduled for late March that delayed their dosing. What proportion of those have now rescheduled their infusions?

然後就商業化應用而言，您提到有些原定於 3 月底服藥的患者推遲了服藥。其中有多少人現在重新安排了輸液？

So let me answer the second question first by simply telling you I don't have the data available to me right now. But it was really -- those were primarily a function of patients or they're physicians who saw the news of the event and needed information. And they're coming up to an infusion in a week. And so they had to either pause or more -- most likely in almost every case rescheduled immediately so they could get access to that information.

因此，讓我先回答第二個問題，簡單地告訴你我現在沒有可用的數據。但實際上——這些主要是患者或醫生看到該事件的新聞並需要資訊的功能。一周後他們將進行輸液。因此，他們必須暫停或更多——幾乎在每種情況下都可能需要立即重新安排，以便他們能夠獲取這些資訊。

As it relates to your first question, I will turn the call to Louise, who can provide an update on the label update.

就您的第一個問題而言，我將把電話轉給 Louise，她可以提供標籤更新的最新資訊。

Sure. In April, we submitted a labeling supplement. We already had 1 planned and anticipated. And so at that time, we also updated the label to include this patient death and the case of ALF. And so FDA confirmed receipt of that and set a target review date.

當然。四月份，我們提交了一份標籤補充資料。我們已經有一個計劃和預期。因此當時我們也更新了標籤，包括該患者死亡和 ALF 病例。因此 FDA 確認收到了該資訊並設定了目標審查日期。

So the target completion date will be no later than the fourth quarter this year for those label updates.

因此，這些標籤更新的目標完成日期將不遲於今年第四季。

Brian Abrams, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Brian Abrams。

Maybe shifting gears to limb-girdle. Following the pre-BLA meeting, have you had any additional meetings with the new FDA leadership on the limb-girdle programs and curious their updated feedback on the accelerated approval path for 2E. And then I guess on 2E, is the emerging data still expected to be disclosed publicly by the middle of 2025? Or should we expect that that's going to be initially submitted to the agency? I didn't see anything in the press release or hear anything in your prepared remarks on data.

也許正在轉向肢帶療法。在 BLA 預會議之後，您是否與新的 FDA 領導層就肢帶計劃舉行過其他會議，並好奇他們對 2E 加速審批路徑的最新反饋。然後我猜在 2E 上，新興數據是否仍有望在 2025 年中期公開披露？或者我們應該期望這將首先提交給該機構？我在新聞稿中沒有看到任何內容，也沒有在您準備好的有關數據的發言中聽到任何內容。

I'm going to turn this over to Louise, but let me briefly say the following regarding our interactions with OTP and the LGMD portfolio. So since the change in administration, we have had a number of discussions with OTP and interactions. Everything has remained on course. The approach that they had previously confirmed with us is the approach that they've taken today. So nothing has changed there, which is all very positive.

我將把這個交給 Louise，但請允許我簡要介紹一下我們與 OTP 和 LGMD 投資組合的互動。因此，自政府變動以來，我們與 OTP 進行了多次討論和互動。一切都按計劃進行。他們之前與我們確認的方法就是他們今天採取的方法。所以那裡什麼都沒有改變，這都是非常正面的。

And I would also say, I know there's a lot of concern over the fact that the FDA has gone through a lot of dislocation.

我還想說，我知道大家對 FDA 經歷的嚴重混亂感到非常擔憂。

I think there was an announcement of some 3,500 potential layoffs and that there may be as a result of that delays or slowing down or reviews. But I must give credit where credit is due. We have not yet seen that at all. with our colleagues over at OTP led by Dr. Verdon, Things seem to be quite on track.

我認為，有消息稱可能會有約 3,500 人被裁員，這可能是由於延遲、放緩或審查造成的。但我必須給予應得讚揚的人讚揚。我們還沒有看到這一點。在 OTP 的 Verdon 博士的帶領下，事情似乎進展順利。

And certainly, the approach that they were historically taking is the approach they're taking today.

當然，他們過去採取的方法就是他們今天採取的方法。

But Louise, you're going to want to provide more color about that.

但是路易絲，你會想要提供更多有關這方面的詳細資訊。

Sure. As we've seen over the past several weeks, we've seen consistent interactions with OTP as we've seen previously. We've had a number of interactions. So on 9003, as noted, they confirmed the accelerated approval pathway is open just as early as last week, they accepted a rolling review for SRP-9003, so things continue to progress as planned. Also, as we announced the same review division cleared the IND for SRP-9005 for QC.

當然。正如我們在過去幾週所看到的，我們看到了與 OTP 的一致交互，就像我們之前所看到的一樣。我們有過多次互動。因此，對於 9003，正如所指出的，他們早在上週就確認加速審批途徑已經開放，他們接受了 SRP-9003 的滾動審查，因此事情繼續按計劃進行。此外，正如我們所宣布的那樣，同一審查部門批准了 SRP-9005 的 QC IND。

So things are progressing as planned with the agency.

因此，事情正在按照該機構的計劃進展。

Debjit, Guggenheim Securities.

Debjit，古根漢證券。

So a couple of questions on 1 on limb-girdle. Is there a threshold for protein expression that the OTP wants to see?

因此，關於肢帶問題 1，我有幾個問題。OTP 希望看到的蛋白質表現是否存在閾值？

And number two, could you sort of quantify the number of nonambulant boys who have been treated on the commercial ELEVIDYS product?

第二，您能否量化一下使用 ELEVIDYS 商業產品治療的不能行走的男孩的數量？

On the second question, we're not providing that level of data, although I will tell you, we've obviously historically been dosing non-ambulatory kids, we're continuing to dose non-ambulatory kids, and we're getting start forms for non-ambulatory kids.

關於第二個問題，我們沒有提供那種程度的數據，儘管我會告訴你，我們顯然一直在為不能行走的孩子服用藥物，我們會繼續為不能行走的孩子服用藥物，並且我們正在為不能行走的孩子提供開始表格。

On the first question, I will turn that question over to Louise Rodino-Klapac.

關於第一個問題，我會把這個問題交給 Louise Rodino-Klapac。

Sure. And I think I forgot to answer -- the question on the previous time about -- we will have the emerging data in the first half of this year, which will go into the BLA, that will be expression of the acerbic glycogen protein and safety. On the question around expression levels, as you know, from the 101 trial, we saw expression levels with both doses, both the low and high dose around the 50% mark. We know from preclinical data that much lower expression leads to functional benefit.

當然。我想我忘了回答——上次的問題——我們將在今年上半年獲得新興數據，這些數據將進入 BLA，這將是酸性糖原蛋白和安全性的表達。關於表達水平的問題，如您所知，從 101 次試驗中，我們看到兩種劑量的表達水平，低劑量和高劑量都在 50% 左右。我們從臨床前數據得知，較低的表達可帶來功能益處。

So we anticipate the results that we see from EMERGENE will be consistent with that. and will certainly lead to functional benefit and above any threshold of relevance.

因此，我們預期 EMERGENE 的結果將與此一致。並且必將帶來功能上的好處並超越任何相關的閾值。

And just to add to its first question around the number of non-ambulant patients, I think we have previously disclosed that it's well over 100 patients between the clinical and commercial settings. So we've had good experience there.

關於第一個問題，即無法行走的患者數量，我想我們之前已經透露過，在臨床和商業環境中，患者數量遠遠超過 100 名。所以我們在那裡有很好的經驗。

I think our enrollment forms, or start forms are something like 40% non-ambulatory, 60% ambulatory.

我認為我們的入學表格或開始表格中大約有 40％ 是不能行走的，60％ 是可以行走的。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Can you remind us as to the time lines for seeing data from your confirmatory studies across both the exon skipping franchise but also ELEVIDYS?

您能否提醒我們查看外顯子跳躍系列和 ELEVIDYS 的驗證性研究資料的時間表？

The confirmatory trial for -- okay. I guess you mean the ENVISION trial. Louise, I'll turn this to you.

確認試驗——好的。我猜你指的是 ENVISION 試驗。路易絲，我會把這個交給你。

Sure. The last patient last visit for ENVISION is in 2027.

當然。ENVISION 的最後一次病患就診是在 2027 年。

Brian Skorney, Baird.

布萊恩·斯科尼，貝爾德。

I guess just in regards to the changes that CBER and meetings with the FDA, you said that you're expecting a decision on labeling update to ELEVIDYS no later than the fourth quarter. I'm just wondering, is there any sort of formal meetings that are held with CBER along with that? Or is it just sort of an internal review until they make that decision?

我想，就 CBER 的變化和與 FDA 的會議而言，您說您預計最遲在第四季度就會對 ELEVIDYS 的標籤更新做出決定。我只是想知道，是否有與 CBER 一起舉行任何形式的正式會議？或者這只是他們做出決定之前的一種內部審查？

And then when we first heard about the patient death, I know there's a complicating factor with the reactivation of latent virus. So I was just wondering if the wound up being a biopsy and if you had anything informative on that front.

當我們第一次聽到病人死亡時，我知道潛伏病毒的重新活化是一個複雜因素。所以我只是想知道傷口是否是活檢，以及您是否有這方面的任何資訊。

I'll answer the last part of it to think it easier on Luise. We don't have the autopsy results yet. We're waiting for them. We should get them in the next month or they may or may not be additionally informative. And as to the first of your questions, I'll turn this to Louise.

我將回答最後一部分，以便讓 Luise 更容易理解。我們還沒有屍檢結果。我們正在等他們。我們應該在下個月得到它們，它們可能會或可能不會提供額外的資訊。至於您的第一個問題，我將把它交給路易絲。

Regarding the label update, the FDA would just come back with any questions along the way if needed. And really, it's more of finalizing the label update, not necessarily that we're awaiting a decision on it. So they've already confirmed that they are in general agreement. So it's really just going through the process now.

關於標籤更新，如果需要，FDA 隨時回答任何問題。實際上，這更多的是最終確定標籤更新，而不一定是在等待對此做出決定。因此他們已經確認他們總體上達成了一致。所以現在其實只是經歷這個過程。

Michael Ulz, Morgan Stanley.

摩根士丹利的邁克爾·烏爾茲。

Maybe just another one on ELEVIDYS trends and more recently, just curious if there's been a shift in the age of the patients being treated or in the ambulatory status of those patients being treated?

也許只是關於 ELEVIDYS 趨勢的另一個，最近，只是好奇接受治療的患者的年齡或接受治療的患者的門診狀態是否發生了變化？

Yes. Thanks for your question. I think it's too early to know precisely what the trend is. What I can tell you, which is a little more anecdote than precise trending is that we are continuing to see both ambulatory and non-ambulatory start forms coming in. So I don't know if we track this out 2 months, if that 40% will go down to 35%.

是的。謝謝你的提問。我認為現在判斷趨勢到底是什麼還為時過早。我可以告訴你的是，這更多的是軼事而不是精確的趨勢，我們將繼續看到行走和非行走的開始形式同時出現。所以我不知道如果我們追蹤兩個月，那個 40% 是否會下降到 35%。

But as it stands right now, we're seeing good uptake in both ambulatory and non-ambulatory from a start form perspective.

但就目前情況而言，從一開始的角度來看，我們看到移動和非移動的接受度都很好。

And I will say, let me forecast the future a bit, of course, the real issue is what happens when the information gets out to patients. And 1 of the things I want to remind us about is that there is no difference in any of the markers, any of the elevated liver enzyme markers, any of the bilirubin marker, there is no difference between ambulatory and non-ambulatory and for instance, risk of elevated liver enzymes or liver injury. So there really should be no reason if we educate properly why there would be a significant difference in start forms.

我想說，讓我稍微預測一下未來，當然，真正的問題是當訊息傳到患者手中時會發生什麼。我想提醒我們的一件事是，任何標誌物都沒有區別，任何升高的肝酵素標誌物，任何膽紅素標誌物，可走動與不可走動之間沒有區別，例如，肝酵素升高或肝損傷的風險。因此，如果我們進行正確的教育，那麼就沒有理由解釋為什麼開始形式會有顯著的差異。

Gil Blum, Needham & Company.

吉爾·布魯姆（Gil Blum），Needham & Company。

Maybe a different approach for kind of the same topic as it relates to the patients who kind of took a minute to think about whether to go on treatment post the event. Was there any commonality across them, more ambulatory, non-ambulatory or is just the timing thing.

也許對於同一主題可以採取不同的方法，因為它與患者有關，患者需要花一點時間考慮是否在事件發生後繼續接受治療。它們之間是否有任何共同點，更多的是走動，不是走動，還是只是時間問題。

So I'm sorry, timing. It's just a timing thing. They were in March and that was approximately in very end of February, early March was the announcement.

所以我很抱歉，時間問題。這只是一個時間問題。他們是在三月份，大約在二月底，三月初就發布了公告。

Joe Schwartz, Leerink Partners.

Leerink Partners 的 Joe Schwartz。

We noticed the company recently hosted a meeting with PPMD after the patient death. I'm just wondering how impactful were these interactions? And I know that there's an upcoming annual conference in June, so I'm wondering what are the company -- what the company's plans now to interact with these organizations? And what do you think you need to emphasize with these families in order to underscore the positive risk benefit of ELEVIDYS?

我們注意到該公司最近在患者死亡後與 PPMD​​ 舉行了一次會議。我只是想知道這些互動的影響有多大？我知道六月即將召開年度會議，所以我想知道公司現在有什麼計劃與這些組織互動？您認為需要向這些家庭強調什麼才能強調 ELEVIDYS 的正向風險效益？

Yes. I mean I think that webinar was very meaningful, but it's not the end. I think we are committed to giving the broad community. Remember, there's some 10,000, 12,000, 13,000 Duchenne patients in the United States. And we need to get the information out to the broad community so they can make intelligent decisions and evidence-based decisions with their physicians.

是的。我的意思是，我認為那個網路研討會非常有意義，但這並不是結束。我認為我們致力於回饋廣大社區。請記住，美國有大約 10,000、12,000、13,000 名杜氏肌肉營養不良症患者。我們需要將資訊傳播給廣大社區，以便他們能夠與醫生一起做出明智的、基於證據的決定。

At the same time, by the way, side now. We have to do the same thing with the physicians because they -- the physician is the ultimate guider for the decisions of the families.

同時，順便說一下，現在就在身邊。我們必須對醫生採取同樣的做法，因為醫生是家庭決策的最終指導者。

And the information that we have to get out to the world is both the safety profile of this therapy but also the efficacy profile of this therapy. We can't leave one behind because we can't make a good risk-benefit decision without it. And that's one of the things that we need to do. I think in part because of the amount of data we have and the fact that, that data has come in over a significant period of time, I sometimes worry that people aren't seeing all of the information and all of the evidence of the benefits of ELEVIDYS together because it's a really impressive package that, I think, to any rational physician will indicate that this therapy is a significant disease modifier that has the potential for stopping this ferocious muscle damage or at least a significant amount of the muscle damage and then slowing or fully arresting the decline that is inevitable with Duchenne for anyone that doesn't get treatment.

我們要向世界傳播的訊息既包括這種療法的安全性，也包括這種療法的療效。我們不能忽視它，因為沒有它我們就無法做出好的風險收益決策。這是我們需要做的事情之一。我認為部分原因是我們擁有的數據量以及這些數據是在相當長的一段時間內收集到的，我有時擔心人們沒有看到所有的信息和 ELEVIDYS 益處的所有證據，因為它是一個非常令人印象深刻的組合，我認為，任何理性的醫生都會認為這種療法是一種重要的疾病改良劑，有可能阻止這種嚴重的肌肉損傷或至少是相當一部分的肌肉損傷或減輕肌肉疾病的患者，然後完全減輕的肌肉損傷或至少是相當一部分的肌肉疾病，然後是未減輕的肌肉損傷或至少是相當大肌肉的肌肉損傷或至少是相當一部分的肌肉疾病，然後是未減輕肌肉的肌肉損傷或至少是相當大肌肉的營養不良症。

So we just need to get that -- we need to get all of that out. I think 1 of the things we focused on very significantly in that recent webinar, of course, was sharing the most recent information about the safety event. And I think that was extraordinarily appropriate. On a go-forward basis, we need to talk about all of it in the context of all the safety and the efficacy available to us, and we are committed to doing that.

所以我們只需要得到它——我們需要把所有這些都得到出來。我認為，在最近的網路研討會上我們重點關注的事情之一當然是分享有關安全事件的最新資訊。我認為這是極其恰當的。從未來來看，我們需要在現有的所有安全性和有效性的背景下討論所有這些問題，我們致力於這樣做。

Yanan Zhu, Wells Fargo.

朱亞南，富國銀行。

Great. First, I would like to ask for a clarification question regarding the uptick that you anticipate in the summertime for patient demand based on some leading indicators you're seeing. The question is, there must also be a leading indicator of some decline, and that's because you're lowering guidance how do we reconcile a decline and also an uptick? Could we assume that you're seeing pickup in pace of the starting -- patient's start forms coming in towards the more recent period.

偉大的。首先，我想問一個澄清問題，根據您看到的一些領先指標，您預計夏季患者需求會上升。問題是，還必須有一個表明某種下降趨勢的領先指標，這是因為您正在降低指導，我們如何協調下降和上升？我們是否可以假設您看到患者的發病速度在最近一段時間內加快了？

And then sorry about that long-winded question, a follow-up in much straightforward question about peak sales estimate, do you have any comment on whether you are changing your guidance on the peak sales and the time to reach that peak?

然後抱歉問了這麼長的問題，關於峰值銷售估計的一個非常直接的後續問題，您是否正在改變對峰值銷售和達到峰值時間的指導，您有何評論？

Yes. So on your first question, both are great questions, let me answer. On your first question, the lowering of guidance is multifactorial, as I've mentioned, but there's no doubt that as a result of the safety events and the need to get more information to patients, we saw a drop off initially. Now when we say we're already seeing an uptick, and we're going to see a more significant uptick in the summer, that's because -- that's what we're seeing. So someone asked earlier why are you assuming a flat to down second quarter?

是的。關於您的第一個問題，這兩個問題都很好，讓我來回答。關於您的第一個問題，正如我所提到的，降低指導是多因素的，但毫無疑問，由於安全事件和需要向患者提供更多信息，我們最初看到了下降。現在，當我們說我們已經看到了上升趨勢，並且我們將在夏季看到更顯著的上升趨勢時，那是因為——這就是我們所看到的。所以之前有人問，為什麼你假設第二季經濟會持平或下降？

It's because this is a long cycle time therapy and a lot of people need more information to contextualize things and that cost it as we're getting that information out. We're already seeing that uptick in start forms. And then when we talk to the families but also sites, it's quite clear that there is a belief among everyone that they're going to see a very significant uptick in the summertime when you get past the school a year in some of those issues.

這是因為這是一種週期較長的治療，很多人需要更多的資訊來了解情況，而我們在獲取這些資訊時需要付出代價。我們已經看到開始形式的上升。當我們與家長和網站交談時，很明顯，每個人都相信，在學校度過一年後的夏天，這些問題將會出現非常顯著的上升。

So I hope that answers your question. So the second issue was on peak year sales. So we're not prepared yet to talk about peak year sales, but I want to put the concept of peak your sales in the context of a onetime therapy. Normally, the peak year sales is an indication of the ultimate opportunity of the therapy. And onetime therapy is different.

我希望這能回答你的問題。因此，第二期是關於銷售高峰年。因此，我們還沒有準備好談論銷售高峰年，但我想將銷售高峰的概念放在一次性治療的背景下。通常，銷售高峰年份預示著該療法的最終機會。而一次性治療則有所不同。

It's an under -- it's essentially area under the curve analysis. So how long it takes to get to peak and will change the actual peak, but the same opportunity exists essentially under the curve. And there is no reason to believe that the opportunity has become any less diminished now even though we are reducing our guidance for this year because of the -- some of it being cycle time, some of it being some educational needs, some of it being some imbalances in sites that we need to address. The ultimate opportunity remains the same.

它本質上是曲線下面積的分析。因此，達到峰值需要多長時間，並且會改變實際峰值，但曲線下本質上存在相同的機會。儘管我們正在減少今年的指導方針，但沒有理由相信機會已經減少，因為其中一些是周期時間，一些是教育需求，一些是我們需要解決的站點不平衡問題。最終的機會依然是一樣的。

We are correct in our epidemiology. We know the patient population and the size of it. There's no reason to believe there's any smaller population, this is amenable to. And so the same opportunity exists, what that -- what a delay in uptake implied by the $500 million delta in our guidance implies. And what that means for peak year sales is something we'll have to calculate and then look at it and talk later, maybe later this year, maybe early next year, something along those lines.

我們的流行病學研究是正確的。我們了解患者群體及其規模。沒有理由相信人口會減少，這是可以接受的。因此，同樣的機會是存在的，我們的指導中 5 億美元的增量所暗示的吸收延遲意味著什麼。這對於高峰年銷售意味著什麼，我們必須進行計算，然後研究並在以後討論，也許是今年晚些時候，也許是明年年初，諸如此類。

But the opportunity remains the same. The same ultimate NPV should exist in either case.

但機會依然一樣。無論哪種情況，最終的 NPV 都應該相同。

Kostas Biliouris, BMO Capital Markets.

Kostas Biliouris，BMO 資本市場。

To the extent you can comment on that, can you talk a little bit about the decline of ELEVIDYS ex U.S. sales quarter-over-quarter? And to what extent those 3 headwinds you mentioned for U.S. may also apply ex U.S. at least anecdotally?

在您對此發表評論的範圍內，您能否談談 ELEVIDYS 美國以外地區銷售額環比下降的情況？您提到的美國面臨的三大不利因素在多大程度上也適用於美國以外的國家（至少從傳聞來看）？

Well, I'm hesitant to discuss our partners' sales and I would allow our partner to comment on it. I'd be surprised if it related to any of the cycle time issues or even the safety event or the like that we have in the United States, but I would have to beg off that question and ask you to ask Roche about that.

嗯，我不太願意討論我們合作夥伴的銷售情況，我會讓我們的合作夥伴對此發表評論。如果它與我們在美國遇到的任何週期時間問題甚至安全事件或類似問題有關，我會感到驚訝，但我不得不迴避這個問題並請您向羅氏詢問此事。

Anupam Rama, JPMorgan.

摩根大通的 Anupam Rama。

Sorry about that. Just a quick clarification question. Louise, I think you said in April, you submitted a labeling update and had some of the patient -- what you knew about the patient death information. But what else was included within that labeling update, did it include the 2-year Embark safety update? Did it include any real-world safety updates.

很抱歉。這只是一個簡單的澄清問題。路易絲，我想你在四月說過，你提交了一份標籤更新，並了解了一些病人的情況——你所知道的有關病人死亡的信息。但標籤更新還包含什麼內容，是否包含 2 年 Embark 安全性更新？它是否包含任何現實世界的安全性更新？

What all was included in that?

那都包括什麼？

This is just updating the safety information. So this is about including the information around this particular case previously. It was just around (inaudible). So now this included ALF and the case. So that was the breadth of the uptake.

這只是更新安全資訊。因此，這是關於之前包含的有關這個特定案例的資訊。就在那時（聽不清楚）。所以現在這包括 ALF 和案件。這就是接受的廣度。

Biren Amin, Piper Sandler.

比倫阿明、派珀桑德勒。

At the end of February, the company mentioned on its year-end call that there was ample site capacity for both infusion and follow-up. So I just want to kind of ask how site capacity change over the last 2 months? Or what -- or do you think it was more driven by patients being more cautious and need more handling before they sign up for administration? And I think on that last point, is there anything the company can do to provide risk mitigation strategies to physicians, given I think the community is looking for clarity that would derisk future events.

2 月底，該公司在年終電話會議上提到，場地容量充足，可用於輸液和後續治療。所以我只是想問一下過去 2 個月內站點容量是如何變化的？或者什麼——或者您認為這更多的是因為患者更加謹慎並且在他們簽署管理協議之前需要更多的處理？關於最後一點，我認為社區正在尋求明確的資訊以降低未來事件的風險，那麼公司可以做些什麼來為醫生提供風險緩解策略呢？

Let me say a couple of things. One, we do in aggregate, have good site capacity. The issue that we have, as I mentioned, in my opening remarks, is a bit of an imbalance where if you just focus on the top sites, by the way, the top sites are responsible for about 60% of our current sales. They've been so sufficiently successful and enthusiastic along with their patients that they are often booked all the way out. Some are booked by a year or more out.

讓我說幾件事。首先，整體而言，我們確實擁有良好的場地容量。正如我在開場白中提到的那樣，我們面臨的問題是有點不平衡，如果你只關注頂級網站，順便說一下，頂級網站占我們當前銷售額的 60% 左右。他們對病人非常成功並且充滿熱情，因此他們的預約經常被搶光。有些預訂已經提前一年甚至更久了。

So it's not simply about capacity because we can't -- let's be clear. You can't redirect a start form that's sitting at site X that's got a 1-year delay to site Y over in filling the blank, Indiana, it's just sitting there. So we've got to make all of the sites more productive, which is on us. We've got to get out and educate, work with them and the like. And so that's the issue.

所以這不僅僅是能力問題，因為我們不能——讓我們明確一點。您無法將位於 X 站點的開始表單重定向到 Y 站點來填補空白，因為該站點已經延遲了 1 年，印第安納州的開始表單只是坐在那裡。因此，我們必須讓所有站點都更有效率，這是我們的責任。我們必須走出去，教育他們，與他們合作等等。這就是問題所在。

Do I think that there was some drop-off in March from families that you would say handholding in my view, would be needed more information and the like? Absolutely, I think that absolutely did happen. And I think we're doing the work there, and I think it works very well because the data and evidence is very supportive of the risk/benefit of this therapy.

我是否認為 3 月份家庭人數有所下降，在我看來，您會說需要更多的資訊等等？絕對的，我認為這確實發生了。我認為我們正在進行這項工作，我認為它非常有效，因為數據和證據非常支持這種療法的風險/好處。

And then on risk mitigation, I would just say we have a wealth of risk mitigation in this very laudable safety profile therapy, may be very clear. Like we proactively placed into the label. A significant amount of monitoring, which physicians follow. We have this concepts called Sarepta Exchange, which is really 1 of a kind, where physicians in any site can get access to some of the world's leaders nearly on a real-time basis if they have questions or the like when they're infusing. I think the thing that's going to give people the greatest confidence is the data itself because the safety event that we saw earlier this year was a tragic 1 for that family, no doubt.

然後關於風險緩解，我只想說，在這個非常值得稱讚的安全性療法中，我們擁有豐富的風險緩解措施，可能非常明確。就像我們主動放入標籤一樣。醫生會進行大量的監測。我們有一個稱為 Sarepta Exchange 的概念，它確實是獨一無二的，任何地點的醫生在輸液時如果有問題或類似情況，都可以幾乎實時地與一些世界領導人取得聯繫。我認為最能給人們信心的是數據本身，因為毫無疑問，我們今年早些時候看到的安全事件對那個家庭來說是一個悲劇。

So -- but that is in the context of mediated gene therapy generally and it has to be put in context of the number of patients that we've dosed.

所以 — — 但這通常是在介導基因治療的背景下，並且必須結合我們已經治療的患者數量來考慮。

I mean I would remind you we hear often of people that announced data 1 patient or 2 patients or 3 patients. We dosed well over 800 patients. So generally speaking, we know the safety profile of this therapy. If something comes out, there's going to be an autopsy that's going to -- that we're going to have access to in the next couple of months. And if something comes out there that can provide additional insight, there were some signals, a signal of a CMV, which is unusual, a signal of another illness perhaps in December.

我的意思是，我想提醒你，我們經常聽到人們公佈 1 名患者、2 名患者或 3 名患者的數據。我們為超過 800 名患者進行了藥物治療。總的來說，我們知道這種療法的安全性。如果有什麼發現，我們會在接下來的幾個月內進行屍檢。如果有任何發現可以提供額外的見解，那麼就會有一些訊號，CMV 的訊號，這是不尋常的，也許是 12 月另一種疾病的訊號。

If something comes out of that autopsy that's enlightening we'll certainly bring it to the community.

如果屍檢結果具有啟發性，我們一定會將其告知社會。

I think though, the experts up which I am not on a not yet confident that there'll be something out of the autopsy that will provide additional insight. I think the greatest insight that families can have to make risk-based decisions just to understand this therapy, what it can do for these families, how I can protect muscle. And on the other side, what a generally laudable safety profile it has in the context of a serious AAV-mediated gene therapy.

不過，我認為，我所諮詢的專家還不確定屍檢結果能否提供額外的見解。我認為家庭能做出的最重要的決定是了解這種療法，並了解它能為這些家庭做些什麼，以及如何保護肌肉。另一方面，在嚴肅的 AAV 介導的基因治療中，它的安全性總體上是值得稱讚的。

David Hoang, Deutsche Bank.

德意志銀行的 David Hoang。

So I just wanted to ask one on any anecdotal experience broadly for patients that have been dosed to date with commercial ELEVIDYS, what you hear from the docs and families -- match up with what you know from EMBARK in the clinical trial experience?

因此，我只是想問一下，對於迄今為止使用過商業 ELEVIDYS 的患者，是否有任何軼事經驗，您從醫生和家屬那裡聽到的與您從 EMBARK 臨床試驗經驗中了解到的情況相符嗎？

And then just with the PMOs, how should we think about cannibalization of the products, given how the ELEVIDYS commercial uptake curve may be changing?

那麼，就 PMO 而言，考慮到 ELEVIDYS 商業吸收曲線可能會發生變化，我們應該如何考慮產品的蠶食？

Yes. On the first one, you referenced it is anecdotal. So to take that with a grain of salt. It's anecdotal, unfortunately, we don't get approvals on anecdote, we get approval on evidence. The anecdotes amaze very clear.

是的。關於第一個問題，您提到的只是軼事。所以對此持保留態度。這是軼事，不幸的是，我們不是根據軼事獲得批准，而是根據證據獲得批准。軼事令人驚奇非常清楚。

I mean 1 of the things that during this very difficult and chaotic time that's existing in the broader market in biotech specifically and certainly at Sarepta specifically, it is comfort to me when I get videos from families. And we've got -- we're seeing a lot of extraordinary stories from families, kids that are riding bikes, kids are running up and down at an age when they ought to be in a powered wheelchair, kids outpacing their father who's trying to catch them in the woods. There's one particular individual video I watch often.

我的意思是，在這個非常困難和混亂的時期，特別是在生物技術市場，尤其是在 Sarepta，當我收到來自家人的影片時，我感到很安慰。我們看到了許多來自家庭的非凡故事，孩子們騎自行車，孩子們在應該坐在電動輪椅上的年齡跑來跑去，孩子們超過了試圖在樹林裡抓住他們的父親。我經常看一個特定的影片。

So what that doesn't mean much. It's only anecdote, but we get a lot of a lot of great anecdote. And I think when families begin -- to get the opportunity to talk to other families and see the experience they're having not only the experience of getting -- going through the process to get infused in the infusion process and the like, but then seeing what it may mean to them and their life going forward. I think it's going to be very, very motivating for families who as yet, maybe don't have a start form.

所以這沒什麼意義。這只是軼事，但我們得到了很多很多精彩的軼事。我認為，當家庭開始有機會與其他家庭交談並了解他們的體驗時，不僅是獲得體驗——經歷輸液過程等，而且還會看到這對他們以及他們未來的生活意味著什麼。我認為這對於那些還沒有開始計劃的家庭來說將會非常非常有激勵作用。

One other thing I should say, I think there are some interesting information on that in our website, I believe, yes.

還有一件事我要說，我認為我們的網站上有一些關於此的有趣信息，是的。

Mitchell Kapoor, H.C. Wainwright & Co.

米切爾·卡普爾，H.C.溫賴特公司

This is Dan on for Mitchell. So we were wondering with the FDA changes specifically Dr. Vinay Prasad, now homing fever. And given this expectation of having more data for approvals, how much your approach to clinical trial designs change? And do you see any impact to your development timeline?

這是丹 (Dan) 代替米切爾 (Mitchell)。因此，我們對 FDA 的變化感到疑惑，特別是 Vinay Prasad 博士現在的歸巢熱。鑑於對獲得更多審批數據的期望，您的臨床試驗設計方法會發生多大變化？您認為這對您的開發時間表有什麼影響嗎？

Let me speak to what we know today. Of course, that appointment occurred only today. So what I can tell you is that subsequent to the change of Commissioner McCorry and then the departure of Dr. Mark, we've had a significant number of interactions with our primary reviewer on the biologics side, which is OTP at CBER, and we have seen so far no changes, in the approach they're taking. In fact, Dr.

讓我講一下我們今天所知道的情況。當然，這項任命直到今天才生效。因此我可以告訴您的是，在 McCorry 局長更換和 Mark 博士離職之後，我們與生物製劑方面的主要審查員（即 CBER 的 OTP）進行了大量互動，到目前為止，我們尚未發現他們採取的方法有任何變化。事實上，Dr.

Verdun appears to be quite innovative in her goal of moving therapies along and relying upon modern tools for drug development.

凡爾登的目標似乎相當具有創新性，她希望推動治療方法的發展，並依靠現代工具進行藥物開發。

I would also note that Dr. McCorry hasn't made many public statements so it's difficult to deduce precisely what his views are on things. But he did say in a few recent interviews that he does believe, for instance, with respect to rare disease that relying upon biomarkers and plausible mechanisms of action makes sense. So on whole, I'm going to remain confident that the FDA is going to be a science-based evidence-based organization.

我還要指出的是，麥考裡博士沒有發表過很多公開聲明，因此很難準確推斷他對事物的看法。但他在最近的幾次訪談中確實表示，他確實相信，例如，對於罕見疾病，依賴生物標記和合理的作用機制是有意義的。所以總的來說，我仍然相信 FDA 將成為一個以科學為基礎、以證據為基礎的組織。

And hopefully, if the interactions that we've had in the last few months or any indication, are going to continue the march towards ensuring that regulatory science can keep pace with actual science and we can begin to really accelerate. To that very end, one of the things that we speak of all of the time is the cost of health care in the United States. And we talk about a lot of concepts in there. And truthfully, we talk about discounts and rebates and outcome-based agreements and all of those things are interesting and probably worth discussing.

並且希望，如果我們在過去幾個月中進行的互動或任何跡象能夠繼續推動監管科學跟上實際科學的步伐，我們就可以開始真正加速。為此，我們經常談論的事情之一就是美國的醫療費用。我們在其中討論了很多概念。說實話，我們談論折扣、回扣和基於結果的協議，所有這些都很有趣，可能值得討論。

But there is one thing more than anything else that from a drug perspective can reduce the ultimate cost of health care in the United States. And that's the ability to make our therapies get them through the regulatory process with less unnecessary burden, get it stripping down to those things that truly add insight on safety and efficacy, collapsing time lines and reducing the cost and risk of them. If you do that, you can start getting therapies out in the United States and then around the world, that will be far less expensive, but equally efficacious and beneficial to patients.

但從藥物角度來看，有一件事比其他任何事情都更能降低美國醫療保健的最終成本。這就是讓我們的療法能夠以更少的不必要負擔通過監管程序，將其精簡到真正增加對安全性和有效性的洞察力，縮短時間線並降低成本和風險。如果你這樣做，你就可以開始在美國乃至全世界推廣這種治療方法，這種方法會便宜得多，但對患者來說卻同樣有效和有益。

So that's the direction in which I see the FDA historically heading, and I'm confident that the FDA will see that, that's a brilliant answer for society.

這就是我所看到的 FDA 歷史性的發展方向，我相信 FDA 會看到這一點，這對社會來說是一個絕妙的答案。

Kristen Kluska, Cantor Fitzgerald.

克里斯汀·克魯斯卡，坎托·費茲傑拉。

This is Rick Miller on for Kristen. Can you just talk about some of the administrative delays in infusion. I think you mentioned a specific Medical delay that you said was resolved. Was there something specific driving this? Any information requests from organization or anything like that you could speak about?

我是里克米勒 (Rick Miller)，為克里斯汀 (Kristen) 表演。您能否談談輸液方面的一些行政延誤？我認為您提到了具體的醫療延誤，並且您說該延誤已經解決。有什麼特定因素推動了這現象嗎？您能談談組織的任何資訊請求或類似的事情嗎？

Yes. That very specific issue, which is the administrative delays, specifically in the first quarter, that was really just an administrative issue. It was an administrative issue between the sites of care in Los Angeles County and Medical -- let me give you more detail than you want. So when you -- normally the thing that decides whether a patient gets dosed is a preauthorization. So you get a pre-op.

是的。這個非常具體的問題，即行政延誤，特別是在第一季度，這實際上只是一個行政問題。這是洛杉磯縣和醫療機構之間的管理問題——讓我給你比你想要的更多的細節。因此，通常決定患者是否接受藥物治療的是預先授權。所以你得進行術前準備。

This is not about that. So this is not about patients ultimately getting dosed. This wasn't a fight over access or anything along those lines.

這不是那件事。所以這與患者最終接受藥物治療無關。這並不是一場爭奪訪問權的鬥爭或諸如此類的事情。

This is all about families that already had scheduled infusions and had already gotten prior offs from the payers. So it's not about access or anything. It's a really specific administrative issue, which is given the cost of these onetime therapies sites of care, often very, very often, maybe almost universally are asking of the payers that they signed single case agreements for that particular infusion, which is sort of a belt and suspension concept of saying, I know I'm going to get reimbursed if I do this.

這一切都與已經安排了輸液並且已經從付款人那裡獲得預先補助的家庭有關。所以這與訪問或其他任何事情都無關。這是一個非常具體的管理問題，考慮到這些一次性治療的費用，護理中心通常、經常、甚至幾乎普遍要求付款人為該特定輸液簽署單例協議，這是一種雙重懲罰的概念，即，我知道如果我這樣做，我將獲得報銷。

And there was this hiccup in the first quarter where there was a delay in those single-case agreements. And that caused -- people just couldn't get dosed. They all got rescheduled by the way. They all just -- they all got rescheduled, but outside of the first quarter into the second quarter. And then that issue got resolved between the payers and the state.

第一季出現了一個小問題，就是這些單案協議被推遲了。這就導致人們無法服藥。順便說一下，他們都重新安排了時間。它們都只是——它們都被重新安排了，但從第一季到第二季。然後這個問題在付款人和國家之間得到了解決。

Yes, go ahead.

是的，請繼續。

And it does -- it's a good question. It does really underscore the dynamics of a onetime therapy that if you compare it to our PMO experience, delays in, let's say, 15 patients in the gene therapy world to get the same kind of financial impact, you'd have to have the delay of 150. It's a tenfold impact for a onetime gene therapy versus a chronic therapy. So small swings matter, but that works both on the upside and the downside.

確實如此——這是一個好問題。它確實強調了一次性治療的動態，如果你將它與我們的 PMO 經驗進行比較，那麼假設在基因治療領域延遲 15 名患者以獲得相同的財務影響，則必須延遲 150 名患者。一次性基因治療的效果比長期治療高出十倍。因此，小幅波動很重要，但它對上行和下行都有影響。

Yes. I do want to make sure we're absolutely clear that was purely an administrative issue. It's not an issue we've seen before. We understand the single case agreement concept well. One of the things you need to know, though, is that we don't participate in the single case agreement.

是的。我確實想確保我們絕對清楚這純粹是行政問題。這不是我們以前見過的問題。我們非常了解單一案例協議的概念。不過，您需要知道的一件事是，我們不參與單一案件協議。

That is between the site and the payer itself. But it's not an access issue. It's an administration issue.

這是網站和付款人之間的事。但這不是一個訪問問題。這是一個管理問題。

Sami Corwin, William Blair.

薩米·科溫、威廉·布萊爾。

This is (inaudible) for Sami Corwin. So in regards to patient education, are there particular -- any particular data sets to the families, what they want to see before gaining more -- to gain a little bit more confidence on ELEVIDYS following the safety event? I know you guys presented a lot of safety data thus far. But do you -- are you hearing anything on family want to see more data in possibly the older non-ambulatory patients to get more confidence there for them?

這是（聽不清楚）給薩米·科溫的。那麼，在對患者進行教育方面，是否有特定的數據集提供給患者家屬，在獲得更多資訊之前他們希望看到什麼，以便在安全事件發生後對 ELEVIDYS 更有信心？我知道你們迄今為止已經提供了大量安全資料。但是，您是否聽說過家人希望看到更多有關年長無法行走的患者的數據，以便為他們提供更多信心？

Well, I'm going to speculate on. I mean I think the things that are important to families broadly. So specifically about the safety event, they want to hear about it, what was it exactly and put it in context. One of the things that family sometimes didn't know is like is this 1 of 5. If you do is you dose 10 kids.

好吧，我來推測一下。我的意思是，我認為這些事情對整個家庭來說都很重要。因此，他們希望了解安全事件的具體情況，並了解事件的具體背景。家人有時不知道的事情之一是這樣的 1/5。如果你這樣做的話，你就給 10 個孩子服用了藥物。

No, we've dosed well over 800 kids. That data points probably becoming stale. We've just over 800 kids. So sort of contextualizing it and what that was about and what that meant.

不，我們已經給超過 800 名兒童注射了藥物。這些數據點可能已經過時了。我們有 800 多名孩子。因此，要將其具體化，了解其內容和意義。

The second piece of information, I think, that's really important to families to contextualize is, do you see anything different here? Is there something about being ambulatory versus non-ambulatory that plays a role? And the answer to that is no. We looked at all the signals, there is no reason to believe that at all. All of the liver enzyme issues are the same across ambulatory or non-ambulatory is the same.

我認為，第二個訊息對於家庭來說非常重要，那就是，你在這裡看到什麼不同了嗎？行走能力與非行走能力之間是否存在某種關係？答案是否定的。我們查看了所有訊號，根本沒有理由相信這一點。無論是門診病人或非門診病人，所有的肝臟酵素問題都是相同的。

But then I think the next big thing that families need to understand is the efficacy.

但我認為家庭需要了解的下一件大事是功效。

They really need to see the efficacy. And that's a lot. There's a lot to talk about there, right? Because we have a lot of data that supports how beneficial this therapy is all of the data that supported the original approval, the totality of the evidence was lights out supportive of it. And then the data that came out a year later from the original study was just, again, completely lights out.

他們確實需要看到效果。這就夠多了。那裡有很多事要談，對吧？因為我們有大量數據支持這種療法的益處，所有支持最初批准的數據，所有證據都明顯支持這種療法。而一年後原始研究得出的數據再次令人大吃一驚。

On the 2 years kids that are on the therapy for 2 years were significantly better than natural industry on every single measure. Same was true for the older kids, even at 1 year. The trajectory analysis was just a really interesting opportunity where you got these kids all blinded for 2 years. Some were on placebo, some were on full drug. You cross them over at 1 year.

接受該療法治療兩年的孩子在每項指標上都明顯優於自然療法。對於年齡較大的孩子也是如此，即使他們只有 1 歲。軌跡分析是一個非常有趣的機會，你可以讓這些孩子在兩年內都處於失明狀態。有些人服用安慰劑，有些人服用全效藥物。您在 1 年後將它們交叉。

They're all blinded. So they don't know if they had the therapy before or now they're getting the therapy. And what did you see? Kids that had previously gone the therapy were doing -- got a big benefit and then we're stable and doing great. They got a placebo, they didn't do anything.

他們全都瞎了。所以他們不知道以前是否接受過這種治療或現在是否正在接受這種治療。你看到了什麼？之前接受過治療的孩子們得到了很大的好處，而且情況穩定，做得很好。他們服用了安慰劑，什麼事也沒做。

They just continue to stay stable. They didn't have a placebo effect even they just became stable. And then the kids that were on placebo when they hit 1 year and they got this -- the therapy, again, they didn't know they got it. they just rocketed up and did brilliant. You saw this huge gap.

他們只是繼續保持穩定。即使他們剛剛變得穩定，也沒有安慰劑效應。然後，那些服用安慰劑的孩子在一歲時又接受了這種治療，但他們並不知道自己接受了這種治療。他們一飛沖天，表現出色。你看到了這個巨大的差距。

So that is really important data for them to see.

所以對他們來說，這是非常重要的數據。

And then I would argue that another thing that they really need to see because it -- because this goes not only to the efficacy of the therapy. But the importance of prioritizing getting this therapy, there's a lot of things you can do for your kid. There's interesting therapies out there. This is a disease-modifying therapy. So before you do anything else, you got to modify the disease.

然後我想說的是，他們真正需要看到的另一件事是，因為這不僅關係到治療的效果。但優先接受這種治療非常重要，你可以為你的孩子做很多事情。有一些有趣的療法。這是一種改善疾病的療法。因此，在採取其他行動之前，您必須先改變疾病。

And I would argue that muscle MRI data that they see is really impactful because that doesn't just say that this therapy is important. It says you don't have the luxury of waiting. And I'm not going to criticize families. I don't know families personal issues and why the family might want to wait until the summer versus getting it in the late winter. But I would argue that if you see the muscle MRI data, you're going to feel very motivated.

我認為他們看到的肌肉 MRI 數據確實很有影響力，因為這不僅僅說明這種療法很重要。它說你沒有等待的奢侈。我不會批評家庭。我不知道家庭的個人問題，也不知道為什麼家庭可能想等到夏天而不是在冬末得到它。但我認為，如果你看到肌肉 MRI 數據，你會感到非常有動力。

I got to get this kid on this therapy as soon as my family situation would allow it. Because what we saw again is in just 1 year. If you were not on this therapy, you're going to have a lot more muscle damage that's not coming back.

只要我的家庭狀況允許，我就必須讓這個孩子接受這種治療。因為我們再次看到的只是1年的時間。如果您不接受這種療法，您的肌肉損傷將會更加嚴重，而且無法恢復。

Our therapy doesn't bring them all back, and you're going to have a lot more fat and fibrotic tissue that's not going to be helpful anyways. I think that sort of whole package of data. And by the way, that's not just for families. This is the kind of information that we really need to share robustly with treating physicians, not only our top treating physicians who get this in spades, but physicians throughout the countries and refers around the country so that everybody understands feels not only the value of the therapy but feels the urgency that these kids need to get infused as soon as an infusion site is available to them and infusion date is available to.

我們的療法並不能使所有問題都恢復，而且你將會擁有更多的脂肪和纖維化組織，這無論如何都不會有幫助。我認為那是一整套數據。順便說一句，這不僅適用於家庭。我們確實需要與治療醫生大力分享這類訊息，不僅是我們最頂尖的治療醫生，他們對此瞭如指掌，而且還有全國各地的醫生和轉診醫生，以便每個人都能理解，不僅感受到治療的價值，而且感受到這些孩子需要盡快接受輸液的緊迫性，只要有可用的輸液部位和輸液日期。

And you can see some of the tools that we're offering to patients now on elevidys.com. You can go in and see the various videos, educational tools, including the tools, how we educate them across treatment journey of what to expect and how to -- how to -- what to expect and how to manage that treatment journey.

您可以在 elevidys.com 上看到我們現在為患者提供的一些工具。您可以進入並查看各種影片、教育工具，包括工具、我們如何在整個治療過程中教育他們會發生什麼以及如何——如何——會發生什麼以及如何管理治療過程。

Uy Ear, Mizuho.

尤伊·厄爾，瑞穗。

This is Leo on for Uy. Is there a reason that patients appear to be flocking towards the leading centers that have full capacity? Do you expect any of these leading sites to increase their site capacity? And to what extent does your updated guidance account for increased number of infusions at the secondary sites that you're not targeting?

這是 Leo 為 Uy 所做的表演。患者似乎紛紛湧向容量已滿的領先醫療中心，這其中有什麼原因嗎？您是否預計這些領先的站點會增加其站點容量？您更新的指南在多大程度上解釋了您未針對的二級站點的輸液次數增加？

So I think it's not at all a surprise that there are so many start forms at the top sites. They are also the top sites. They are -- these are the world-leading Duchenne sites, like you can then I don't want to start naming them because I might forget one, and then I'll be accidentally insulting somebody. But these are the world's leaders in the treatment of Duchenne muscular dystrophy. These are the most renowned sites around the country and frankly, around the world.

因此我認為頂級網站上有如此多的開始表格一點也不奇怪。它們也是頂級網站。它們是——這些是世界領先的杜氏肌肉營養不良症治療中心，就像你一樣，我不想開始列舉它們的名字，因為我可能會忘記一個，然後我會不小心侮辱某人。但這些都是杜氏肌肉營養不良症治療領域的世界領導者。這些是全國乃至全世界最著名的景點。

So it should be of no surprise that a family when they hear about this horrible diagnosis would want to go to one of those sites potentially. And that's why it's there.

因此，當一個家庭聽到這個可怕的診斷結果時，他們可能會想去其中一個地方，這並不奇怪。這就是它存在的原因。

So -- and I'm sorry, what was the other part of the question missing it -- but -- anyways, that's the reason that there was this imbalance. And then I guess on our forward -- yes, we're assuming that we're going to get a lot more capacity. We're going to exploit a lot of the capacity in the secondary sites going forward that's going to help us not only hopefully even get to or even exceed our guidance over the course of the year.

所以 — — 很抱歉，問題的另一部分遺漏了什麼 — — 但是 — — 無論如何，這就是造成這種不平衡的原因。然後我想，就我們的未來而言——是的，我們假設我們將獲得更大的容量。我們將充分利用二級站點的大量容量，這不僅有助於我們在今年達到甚至超過我們的預期。

And one thing I should remind everybody, all of the sites that are permitted to infuse Sarepta -- I mean ELEVIDYS are well-trained and validated sites, and they are themselves all brilliant sites. So there is no reason to believe you're going to get a different quality of care in 1 of these sites, they're going to all do a great job for you, we need to focus on.

有一件事我應該提醒大家，所有被允許注射 Sarepta 的站點——我的意思是 ELEVIDYS 都是經過良好培訓和驗證的站點，而且它們本身都是非常出色的站點。因此，沒有理由相信您會在其中一個站點獲得不同品質的護理，他們都會為您提供出色的服務，我們需要關注這一點。

Andreas Argyrides, Oppenheimer & Co.

安德烈亞斯·阿吉里德斯（Andreas Argyrides），奧本海默公司

With shares at current levels, how are you guys thinking about the opportunity for implementing the approved buyback.

在目前股價水準下，你們如何看待實施已核准的回購的機會？

I'll turn this to Ian.

我將把這個交給伊恩。

As I said in our prepared remarks, obviously, the stock does not reflect, our guidance still remains $2.3 billion to $2.6 billion. The stock is trading at level. recognizing that. And so we certainly think that it's undervalued. Louise just outlined multiple data readouts from our pipeline also to continue to drive growth.

正如我在準備好的演講中所說的那樣，顯然，股票沒有反映出來，我們的指導仍然保持在 23 億美元至 26 億美元之間。該股票目前交易價格穩定。認識到這一點。因此我們確實認為它被低估了。路易絲剛剛概述了我們管道中的多個數據讀數，以繼續推動成長。

So we have to balance, obviously, both our investment in R&D and then our investment in a potential allocation strategy, and that's what we mean to going forward. Obviously, we're not going to be too direct about how much we're doing or the like, but it's certainly a consideration that we're looking at.

因此，顯然，我們必須平衡對研發的投資和對潛在分配策略的投資，這就是我們未來的目標。顯然，我們不會太直接地說明我們做了多少或諸如此類的事情，但這肯定是我們正在考慮的問題。

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

This is Tony on for Gena. So some of our own channel checks have suggested that there are some payers deciding not to cover ELEVIDYS. We were wondering if you could provide any additional color on your experience with coverage so far?

這是 Tony 代替 Gena 上場的。因此，我們自己的一些通路檢查表明，有些付款人決定不承保 ELEVIDYS。我們想知道您是否可以提供更多關於您迄今為止的報道經驗的資訊？

And then second question, when could we potentially expect an update regarding the halt on studies in the EU.

第二個問題是，我們什麼時候可以期待有關歐盟暫停研究的最新消息。

Sure. So first on the first one, just to be clear, I can use the PMOs is the answer. There are always some subset of payers that resist access and require more work. And just 1 of the reasons that cycle times sometimes get extended because you have to go through appeals processes and the like. So there's nothing different about ELEVIDYS and the PMO with the exception that probably on a whole the ELEVIDYS policies are better.

當然。因此，首先關於第一個問題，只是為了明確起見，我可以使用 PMO 來回答。總是有一些付款人拒絕訪問並要求做更多的工作。這只是周期時間有時會延長的原因之一，因為您必須經過上訴程序等。因此，ELEVIDYS 和 PMO 沒有什麼不同，只是 ELEVIDYS 的政策可能總體上更好。

So ELEVIDYS policies are a lot better part because we have a traditional approval for a significant percentage of that approval and in part because we have so much data that supports it. What I will say and ultimately, regardless of policy, the difference is in policies. There's policies to label.

因此，ELEVIDYS 政策要好得多，部分原因是我們對很大一部分批准都有傳統批准，部分原因是我們有大量數據來支持它。我想說的是，最終，無論政策如何，差別在於政策。有政策需要標記。

There's a lot of them with ELEVIDYS, and I'm really proud of that. there simply that try to put some restrictions in and then there are some policies that are very restrictive. The ultimate answer is an issue for us, but not actually ultimately for revenue for you because we'll get the kids on the therapy in any of the scenarios. Some will take a little longer than others. And that's why I can tell you that with respect to the PMOs, we're well over 90% success rate in getting those kids on therapy even when a payer might try to take us to an appeal or something.

其中有很多是 ELEVIDYS 的，我對此感到非常自豪。他們只是試圖施加一些限制，然後制定了一些非常嚴格的政策。最終答案對我們來說是一個問題，但實際上對您來說並不是最終的收入問題，因為無論在哪種情況下，我們都會讓孩子接受治療。有些會比其他的花費更長的時間。這就是為什麼我可以告訴你，就 PMO 而言，即使付款人可能會試圖讓我們上訴或採取其他措施，我們在讓這些孩子接受治療方面的成功率也遠遠超過 90%。

We love it is our current success rate stands at 100%. suggesting that five years from now, we'll still be at exactly 100%, but there's no reason to believe we will be worse than our PMOs and our PMOs are doing great. So we feel very good about it.

我們非常喜歡它，因為我們目前的成功率達到了 100%。這表明五年後我們的效率仍將保持在 100%，但沒有理由相信我們的效率會比我們的 PMO 更差，而且我們的 PMO 做得很好。因此我們對此感覺非常好。

And then as it relates to the hall, Louise, do you want to chat about that?

然後說到大廳，路易絲，你想聊聊這個嗎？

Sure. The EU process requires a need for a substantial amendment. That typical review time is around 95 days. So that approval to restart is expected around the end of summer. But just to remind you, we are still enrolling outside of the EU as well. So the trial continues to enroll and we're on track.

當然。歐盟進程需要進行實質修改。典型的審查時間約為 95 天。因此，預計在夏季末批准重啟。但需要提醒您的是，我們也仍在歐盟以外地區招生。因此，試驗仍在繼續，一切進展順利。

I'm showing no further questions at this time. I would now like to turn it back to Doug Ingram for closing remarks.

我目前沒有其他問題。現在我想請道格‧英格拉姆 (Doug Ingram) 作最後發言。

All right. Well, thank you all for joining us this evening. I will tell you, it's not enjoyable to bring guidance down. It's the first time frankly, in my career when I've done it, and I don't intend to do it again. But I do think it was the prudent thing for us to do as we're working through some of these issues, and I feel very confident the teams prepared to work through the issues, and we will achieve our guidance.

好的。好吧，感謝大家今晚加入我們。我跟你說，把指導放下來可不是什麼愉快的事。坦白說，這是我職業生涯中第一次這樣做，我不打算再這樣做了。但我確實認為，在解決其中一些問題時，這是我們謹慎的做法，我非常有信心團隊已經準備好解決這些問題，我們將實現我們的指導。

I mean, I'm just talking extemporaneously now. I came to -- it's more than revenue to me, okay? It's not about revenue. That's not what upsets me. but revenue is the scorecard for what upsets me. The fact is that I came to Sarepta, just about 8 years ago with the belief that along with some other really dedicated people, we might actually be able to intervene and change the course of a disease that's just horrific for families.

我的意思是，我現在只是即興講話。我來到──這對我來說不只是收入，好嗎？這與收入無關。這並不是令我心煩的事。但收入才是讓我心煩意亂的記分卡。事實上，大約 8 年前，我來到 Sarepta 時，就相信我們和其他一些真正有奉獻精神的人能夠真正幹預並改變這種給家庭帶來可怕後果的疾病的進程。

And I feel particularly strong about that right now because I literally had to go to a funeral yesterday for a young man who died up Duchenne muscular dystrophy. It's a disease that takes often brilliant human beings and steals them from their family little bit by bit.

我現在對此感覺特別強烈，因為昨天我不得不去參加一位因杜氏肌肉營養不良症去世的年輕人的葬禮。這是一種疾病，它常常會奪走一些才華橫溢的人的生命，並一點一點地將他們從家人身邊奪走。

And for almost all of history, there was nothing but [nihilism]. It was nothing but a physician that got the tell a diagnosis. There's nothing we can do for this boy. So go home and love him and watch him, grow and then die in front of you. And the thought that we might be able to do something about that was extraordinarily motivated. It's why I came here and why me and 15 other people at Sarepta fight every day for the families that we serve.

幾乎在整個歷史中，只存在著虛無主義。這只是一位醫生給的診斷。我們對這個男孩無能為力。所以回家愛他，看著他成長，然後在你面前死去。而我們可能能夠對此採取一些行動的想法是非常有動力的。這就是我來這裡的原因，也是我和 Sarepta 的其他 15 名員工每天為我們服務的家庭而奮鬥的原因。

This is not just a revenue issue for us. This is who we are. And so the very idea that we've gotten to where we've gotten is impressive, okay? We have four approved therapies. We have three PMOs doing a lot of good for kids.

對我們來說這不僅僅是一個收入問題。這就是我們。所以，我們能取得現在的成就本身就令人印象深刻，好嗎？我們有四種核准的療法。我們有三個專案管理辦公室為孩子們做了很多好事。

And we have a gene therapy that's the best gene therapy and the most successful gene therapy ever launched. But it's not good enough. I want to be very clear. That's not good enough, all right? Because every day when a kid who could have gotten infused, doesn't because of an administrative issue or because of a misinformation issue because we didn't get out to the site. That's a day we failed in our mission, and we're not going to fail in our mission.

我們擁有一種基因療法，這是迄今為止最好的基因療法，也是最成功的基因療法。但這還不夠好。我想說得非常清楚。這還不夠好，好嗎？因為每天當一個孩子本來可以注射疫苗時，由於管理問題或由於錯誤訊息問題，我們沒有到達現場，所以沒有註射。那是我們的使命失敗的一天，我們不會再失敗。

So I look forward to updating you over the course of this year, and we've got a lot of other things going on at Sarepta that we're excited to talk to you about later this year. And I thank you all for your support and for your great questions this evening.

因此，我期待今年向您通報最新情況，Sarepta 還有很多其他事情要做，我們很高興在今年晚些時候與您討論。我感謝大家今晚的支持與提出的精彩問題。

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

感謝大家參加今天的會議。該計劃確實就此結束。您現在可以斷開連線。