Sarepta Therapeutics Inc (SRPT) 2025 Q3 法說會逐字稿

Good afternoon and welcome to Sarepta's third quarter 2025 financial results conference call. As a reminder, today's program is being recorded. At this time, I'll turn the call over to Tam Thornton, Director of Investor Relations. Please go ahead.

下午好，歡迎參加Sarepta 2025年第三季財務業績電話會議。提醒各位，今天的節目正在錄製。現在，我將把電話轉交給投資者關係總監譚·桑頓。請繼續。

Thank you, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the third quarter of 2025. The press release and slides are available on the Investors section of our website at sarepta.com, and our 10-Q will be filed with the Securities and Exchange Commission on Thursday after market.

謝謝，也謝謝各位參加今天的電話會議。今天下午早些時候，我們發布了 2025 年第三季的財務表現。新聞稿和投影片可在我們網站 sarepta.com 的投資者關係部分查看，我們的 10-Q 表格將於週四盤後提交給美國證券交易委員會。

Joining us on the call today are Doug Ingram, Dr. Louise Rodino-Klapac, Patrick Moss, Ian Estepan and Ryan Wong. 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.

今天參加電話會議的有 Doug Ingram、Louise Rodino-Klapac 博士、Patrick Moss、Ian Estepan 和 Ryan Wong。正式致詞結束後，我們將開放問答環節。我想指出，在本次電話會議中，我們將做出一些前瞻性陳述。請參考網路直播中的第 2 張投影片，其中包含我們的前瞻性聲明。

These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta's control. 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. 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.

這些前瞻性聲明涉及風險和不確定性，其中許多風險和不確定性超出了 Sarepta 的控制範圍。實際結果可能與這些前瞻性聲明有重大差異，任何此類風險都可能對 Sarepta 的業務、經營績效和普通股交易價格產生重大不利影響。如需詳細了解適用的風險和不確定性，我們建議您查閱本公司最近向美國證券交易委員會提交的文件。本公司不承擔任何義務公開更新其前瞻性聲明，包括今天根據後續事件或情況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 on the Investors section of our website.

如投影片 3 所示，我們將在本次網路研討會上討論非公認會計準則財務指標。這些非GAAP財務指標的說明以及GAAP與非GAAP財務指標的調節表包含在今天的新聞稿和我們網站投資者關係部分的幻燈片簡報中。

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

現在我將把電話交給我們的執行長道格·英格拉姆，他將概述我們最近的進展。道格？

Thank you, Tam. Good afternoon, everyone. Thank you for joining us for our third quarter 2025 financial results conference call. Next slide, please. We have much to discuss this evening, but let's begin by reviewing the completion of our confirmatory study for our two ultra-rare disease CMOs, VYONDYS and AMONDYS, before coming back to our quarterly update.

謝謝你，譚。大家下午好。感謝您參加我們2025年第三季財務業績電話會議。請看下一張投影片。今晚我們有很多事情要討論，但讓我們先回顧一下我們兩款超罕見病 CMO（VYONDYS 和 AMONDYS）的確認性研究的完成情況，然後再回到我們的季度更新。

Next slide. I'm going to turn the call over to Dr. Rodino-Klapac very shortly, but let me first give some broad conclusions. First, we are very proud to have completed our primary confirmatory obligations, both AMONDYS and VYONDYS serve ultra-rare populations with total prevalence numbering for each no more than about 500 to 800 patients in the United States and an incident rate per year of maybe a few dozen patients. This disease is also heterogeneous and degenerates not over months or years, but literally over decades.

下一張投影片。我很快就會把電話轉給羅迪諾-克拉帕克博士，但首先讓我給出一些總體結論。首先，我們非常自豪地完成了我們的主要確認義務，AMONDYS 和 VYONDYS 都服務於極其罕見的人群，在美國，每種疾病的總患病人數不超過 500 至 800 名患者，每年的發病率可能只有幾十名患者。這種疾病也具有異質性，其病情惡化不是在幾個月或幾年內發生的，而是在數十年內發生的。

These together make the powering and conduct of a placebo-controlled trial particularly challenging.

這些因素共同使得進行安慰劑對照試驗變得特別具有挑戰性。

I want to give a huge thanks to our investigators and then very importantly, to the brave families who have had the courage to enroll and risk a placebo arm for 22 months. Without this special community that we serve, we would not have completed this unusually onerous study. Second, when reviewing the evidence to support transition from accelerated to traditional approval of a therapy, one, of course, looks to the totality of the evidence. Here, the division recognized the challenges associated with this ultra-rare disease trial and set out a very specific standard for continuing marketing authorizations. As referenced in our VYONDYS approval material, the FDA gave us a very specific written language about voluntarily withdrawing marketing authorization, which would only occur if "no relevant analyses find sufficient evidence of a clinical benefit.

我要衷心感謝我們的研究人員，更重要的是，我要感謝那些勇敢的家庭，他們有勇氣參與研究，並冒著接受安慰劑治療的風險，堅持了 22 個月。如果沒有我們所服務的這個特殊群體，我們就無法完成這項異常艱鉅的研究。其次，在審查支持從加速審批過渡到傳統審批的療法的證據時，當然要考慮所有證據。在此，該部門認識到了與這種極其罕見的疾病試驗相關的挑戰，並為繼續上市許可製定了非常具體的標準。正如我們在 VYONDYS 批准資料中提到的那樣，FDA 向我們提供了關於自願撤銷上市許可的非常具體的書面措辭，這種情況只會在「沒有相關分析發現足夠的臨床獲益證據」的情況下發生。

As you will hear from Dr. Rodino-Klapac, we believe that we have met that standard and that we have sufficient evidence to discuss with the agency transitioning from accelerated to traditional approval. Consider as you will have seen in our press release, the study missed its statistical significance. However, the data demonstrated a consistent and clinically favorable trend across the trial population. Importantly, a portion of this study was conducted over the COVID pandemic period.

正如您將從 Rodino-Klapac 博士那裡聽到的那樣，我們相信我們已經達到了這一標準，並且我們有足夠的證據與該機構討論從加速審批過渡到傳統審批的問題。正如您在我們的新聞稿中看到的那樣，這項研究未能達到統計意義。然而，數據顯示，試驗族群呈現一致且臨床上有利的趨勢。值得注意的是，這項研究的一部分是在新冠疫情期間進行的。

And as with many studies over that period, the study results were impacted for a variety of reasons. During the pandemic, the rate of missed doses was unusually high with nearly all patients missing doses and approaching half of whom missed substantial consecutive doses.

與同期許多研究一樣，該研究結果也受到多種因素的影響。疫情期間，漏服疫苗的比例異常高，幾乎所有患者都漏服了疫苗，其中近一半患者連續漏服了大量疫苗。

Participants in the study were also largely shut in and suffered deep conditioning and loss of mobility. All of this appears confound in the results. When one excludes the COVID participants, we see a meaningful treatment benefit slowing disease progression by about 30%, which Dr. Rodino-Klapac will further explain. Likewise, to enroll this study, we were required to admit a broad population from as young as six years old to as old as 13 years old, including those who clearly have confounding ceiling and floor effects.

研究參與者也大多被封閉起來，遭受了深度體能訓練和行動能力喪失。所有這些因素似乎都會對結果造成混淆。如果排除 COVID 患者，我們可以看到治療效果顯著，可使疾病進展減緩約 30%，Rodino-Klapac 博士將對​​此進行進一步解釋。同樣，為了進行這項研究，我們需要招收年齡從 6 歲到 13 歲不等的廣泛人群，包括那些明顯存在天花板效應和地板效應的人群。

In the subgroup analysis of those likely to progress, there was a strong statistically significant benefit, and this was across not only the primary but the other endpoints as well. There is also a wealth of published real-world evidence for the PMOs as just a few examples of the multiple real-world studies across our PMOs, we see that when tracking VYONDYS over six years, there is an 88% reduction in risk of loss of ambulation with a Kaplan-Meier analysis of delay of about three years.

在可能出現病情進展的亞組分析中，有顯著的統計學意義上的獲益，這不僅體現在主要終點，也體現在其他終點。此外，還有大量已發表的真實世界證據支持 PMO，例如，在我們 PMO 的多項真實世界研究中，我們發現，在對 VYONDYS 進行六年追蹤後，透過 Kaplan-Meier 分析，行走能力喪失的風險降低了 88%，延遲時間約為三年。

Likewise, with both VYONDYS and AMONDYS, we see over time a significant attenuation in pulmonary decline and a significant delay in time to cough assist and ventilation. We see the same trend in our own study, ESSENCE. As part of the benefits they are seeing, patients are required to be infused weekly, a fairly onerous protocol and yet their compliance rate has been well over 90% commercially year over year over year. When one considers all of the evidence for benefit and then weighs a favorable stable safety profile has tracked over many years. We believe the risk benefit remains positive.

同樣，對於 VYONDYS 和 AMONDYS，隨著時間的推移，我們看到肺功能下降明顯減緩，咳嗽輔助和通氣的時間明顯延遲。我們在自己的研究《精華》中也看到了同樣的趨勢。作為他們所獲得的益處之一，患者需要每週接受輸液治療，這是一個相當繁瑣的方案，但他們的商業依從率年復一年都遠超 90%。當考慮到所有益處的證據，並權衡多年來一直保持的良好穩定的安全性時，就會發現這一點。我們認為風險收益仍然為正。

We not only anticipate continuing marketing authorization, but we believe we have a good argument for traditional approval. Our plan is to schedule a meeting with the division to review the totality of the evidence.

我們不僅預期會繼續獲得上市許可，而且我們相信我們有充分的理由獲得傳統批准。我們的計劃是安排與該部門會面，審查所有證據。

Dr. Rodino-Klapac will now discuss those results in more detail. Louise?

羅迪諾-克拉帕克博士接下來將更詳細地討論這些結果。路易絲？

Thank you, Doug. I'll turn to the next slide. Today, we announced the top line results from our ESSENCE trial, the first placebo-controlled Phase III study of exon skipping therapies, VYONDYS 53 or golodirsen and AMONDYS 45 or casimersen to treat patients with Duchenne muscular dystrophy amenable to exon 53 or 45 skipping, respectively. To remind you, VYONDYS and AMONDYS are designed to address the underlying cause of Duchenne by restoring the messenger RNA or mRNA reading frame. The therapies use Sarepta's proprietary PMO chemistry and exon skipping technology to skip exons 53 and 45 of the dystrophin gene.

謝謝你，道格。接下來我來看下一張投影片。今天，我們公佈了 ESSENCE 試驗的主要結果，這是首個針對外顯子跳躍療法 VYONDYS 53（golodirsen）和 AMONDYS 45（casimersen）的安慰劑對照 III 期研究，分別用於治療適合進行外顯子 53 或 45 跳躍的杜氏肌肉營養不良症患者。提醒一下，VYONDYS 和 AMONDYS 旨在透過恢復信使 RNA 或 mRNA 閱讀框架來解決杜氏肌肉營養不良症的根本原因。這些療法利用 Sarepta 專有的 PMO 化學和外顯子跳躍技術來跳過肌肉營養不良蛋白基因的第 53 和 45 號外顯子。

Promoting the synthesis of a short and functional dystrophin protein is intended to slow decline in Duchenne patients. VYONDYS and AMONDYS were approved by FDA via the accelerated approval pathway in 2019 and 2021, respectively.

促進短鏈功能性肌肉營養不良蛋白的合成旨在減緩杜氏肌肉營養不良症患者的病情惡化。VYONDYS 和 AMONDYS 分別於 2019 年和 2021 年通過 FDA 的加速批准途徑獲得批准。

Next slide, please. As shown on this slide, initiated in September 2016, the 225-person ESSENCE study was designed as a double-blind, placebo-controlled trial spanning 96 weeks, followed by a 48-week open-label extension, reflecting the scale, rigor and long-term commitment required to validate targeted treatments and select rare disease populations such as Duchenne. The trial was conducted across 75 centers in 24 countries.

請看下一張投影片。如本投影片所示，ESSENCE 研究於 2016 年 9 月啟動，共有 225 名受試者參與，設計為一項為期 96 週的雙盲、安慰劑對照試驗，隨後進行為期 48 週的開放標籤擴展研究，這體現了驗證標靶治療和選擇罕見疾病人群（如杜氏肌肉營養不良症）所需的規模、嚴謹性和長期投入。該試驗在 24 個國家的 75 個中心進行。

Next slide, please. In terms of baseline demographics, patients were well matched with 2:1 treated versus placebo with numbers of exon 45 and exon 53 amenable patients consistent with the prevalent Duchenne population. Functional baseline characteristics were also well matched.

請看下一張投影片。就基線人口統計學而言，治療組和安慰劑組的患者匹配良好，比例為 2:1，外顯子 45 和外顯子 53 適用患者的數量與杜氏肌肉營養不良症的流行人群一致。功能基線特徵也匹配良好。

Now turning to the top line results on the next slide. ESSENCE demonstrated numerical superiority across the primary and most secondary endpoints. However, the study did not reach statistical significance on the primary endpoint, the 4-step Ascend at 96 weeks. Let me first highlight the key results, and then I'll provide more detail on each.

現在來看下一張投影片上的主要結果。ESSENCE 在主要終點和大多數次要終點方面均表現出數值優勢。然而，該研究在主要終點（96 週時的 4 步 Ascend）上並未達到統計學意義。首先讓我重點介紹一下主要結果，然後再對每項結果進行更詳細的說明。

First, and as mentioned, we believe COVID impacted study results. A post-hoc analysis of participants not impacted by COVID improved study results on the 4-step Ascend, with a lease square mean difference of 0.11 steps per second and a p-value of 0.09. Second, when a prognostic score is applied to identify the subpopulation at risk for decline on 4-step Ascend, a meaningful and significant treatment response is evident with a lease square mean difference of 0.186 steps per second and a p-value of 0.01. And importantly, there were no new safety signals with comparable AE rates between treated and placebo. AEs were largely mild or moderate.

首先，如同前面提到的，我們認為新冠疫情影響了研究結果。對未受 COVID 影響的參與者進行事後分析，結果顯示，在四步 Ascend 測試中，研究結果有所改善，最小均方差為每秒 0.11 步，p 值為 0.09。其次，當應用預後評分來識別四步 Ascend 測試中存在下降風險的亞組人群時，治療反應顯著，最小均方差為每秒 0.186 步，p 值為 0.01。更重要的是，治療組和安慰劑組的不良事件發生率相當，未發現新的安全性訊號。不良事件大多為輕度或中度。

Next slide, please. As you will see on this slide and as I mentioned previously, although the data showed numerical superiority, the primary endpoint of this study was not met. Next slide, please. As Doug mentioned, COVID appears to have had an impact on study results. The study itself was challenged operationally during the COVID period with twice as many consecutively missed doses during COVID versus COVID-free patients and compressed clinical evaluation schedule.

請看下一張投影片。正如您將在這張投影片上看到以及我之前提到的，儘管數據顯示數值上的優勢，但這項研究的主要終點並未達到。請看下一張投影片。正如道格所提到的，新冠疫情似乎對研究結果產生了影響。在 COVID 疫情期間，該研究本身在操作上面臨挑戰，COVID 患者連續漏服的劑量是未感染 COVID 患者的兩倍，臨床評估時間表也被壓縮。

43% of COVID-impacted patients had consecutively missed doses with an average of eight missed doses. In addition, published studies specifically on the impact of the COVID pandemic in Duchenne have demonstrated a negative impact on function due to immobility, contractures and increased weight gain. On this slide, I've highlighted the COVID period that falls in the middle of the ESSENCE study, which began in late 2016 and completed in 2025. We define patients that began and completed their 96 weeks outside of this window as COVID-free.

43% 的 COVID-19 患者連續漏服疫苗，平均漏服 8 劑。此外，已發表的專門針對 COVID 大流行對杜氏肌肉營養不良症影響的研究表明，由於行動不便、攣縮和體重增加，該疾病對患者的功能產生了負面影響。在這張投影片中，我重點標示了 ESSENCE 研究的中期 COVID 疫情時期，該研究於 2016 年底開始，於 2025 年完成。我們將在此時間窗口之外開始並完成 96 週治療的患者定義為未感染 COVID-19。

Next slide, please. Notably, a post-hoc analysis of the COVID-free participants improved study results on the 4-step Ascend primary endpoint as shown on the left, with a least square mean difference of 0.11 steps per second and a p-value of 0.09. This equates to an approximately 30% reduction in disease progression over two years on the 4-step Ascend. This is in stark contrast to those individuals impacted by COVID on the right. Had we seen this effect size in a sample size similar for the whole trial population, we would expect it would have reached statistical significance.

請看下一張投影片。值得注意的是，對未感染 COVID 的參與者進行事後分析，改善了 4 步 Ascend 主要終點的研究結果（如左圖所示），最小二乘均值差異為每秒 0.11 步，p 值為 0.09。這相當於在 4 步驟 Ascend 治療下，兩年內疾病進展減少了約 30%。這與受新冠疫情影響的右翼人士形成了鮮明對比。如果我們在整個試驗族群中觀察到類似大小的效應量，我們預期它將達到統計意義。

Secondary endpoints also demonstrated improved study results in COVID-free participants.

次要終點也顯示，未感染新冠病毒的參與者的研究結果有所改善。

Next slide, please. Separately, we also performed an analysis using a prognostic scoring method published by the well-respected CTAP, a collaborative trajectory analysis project group, which is focused on Duchenne. This method published after we commenced ESSENCE is used to identify the population most at risk for decline and consequently, a maximum treatment benefit can be identified by avoiding floor and ceiling effects. The method includes baseline age 4-step Ascend velocity, rise from floor velocity, 10-meter walk run velocity and corticosteroid duration and type. The 4-step Ascend was the most sensitive endpoint and reached statistical significance with this prognostic score applied.

請看下一張投影片。另外，我們也使用備受尊敬的 CTAP（一個專注於杜氏肌肉營養不良症的合作軌跡分析計畫組）發布的預後評分方法進行了分析。在我們啟動 ESSENCE 計畫之後發布的這種方法用於識別最有可能出現衰退的人群，從而透過避免地板效應和天花板效應來確定最大的治療益處。該方法包括基線年齡 4 步上升速度、從地面起立速度、10 公尺步行跑步速度以及皮質類固醇的持續時間和類型。4 步驟 Ascend 是最敏感的終點，應用此預後評分後達到統計學意義。

With a clinically meaningful lease square mean difference of 0.186 steps per second and a p-value of 0.01, this equates to a 35% reduction in disease progression over two years on the 4-step Ascend.

臨床上有意義的最小平方均值差異為每秒 0.186 步，p 值為 0.01，這意味著在 4 步 Ascend 治療兩年內，疾病進展減少了 35%。

Next slide, please. There were no new safety signals with comparable adverse event rates between treated and placebo, reinforcing the favorable and manageable safety profile observed with our exon skipping therapies. Adverse events were largely mild or moderate. We believe the totality of these data along with the real-world evidence are compelling for AMONDYS and VYONDYS, and we'll be sharing these data with FDA to support sNDA filings.

請看下一張投影片。治療組和安慰劑組之間沒有出現新的安全訊號，不良事件發生率也相當，這進一步證實了我們的外顯子跳躍療法具有良好的、可控的安全性。不良事件大多為輕度或中度。我們相信這些數據以及現實世界的證據對 AMONDYS 和 VYONDYS 來說都很有說服力，我們將與 FDA 分享這些數據以支持補充新藥申請 (sNDA)。

Next slide, please. Of note, and as you will see here, a number of factors generated from real-world evidence supports casimersen, including a mean age of 15 years for casimersen-treated patients to meet a wheelchair versus 9.5 to 12.3 years in the literature for standard of care. It also shows a 2.6-year delay in time to reach FVC percent predicted of less than 60% for patients 10 to 18 years old versus matched control and a 70% reduction in mortality rate for our PMO.

請看下一張投影片。值得注意的是，正如您將在這裡看到的，許多來自真實世界證據的因素支持卡西美森，包括接受卡西美森治療的患者平均年齡為 15 歲，達到輪椅使用標準，而文獻中標準治療的平均年齡為 9.5 至 12.3 歲。研究還顯示，10 至 18 歲的患者達到 FVC 估計值低於 60% 的時間比匹配的對照組延遲了 2.6 年，而我們的 PMO 患者的死亡率降低了 70%。

Next slide, please. On this slide, you will see how the real-world evidence supports golodirsen, including a three-year delay in loss of ambulation versus external control, a 7.5-year delay in the need for nighttime ventilation and a 70% reduction in mortality. Next slide, please. As you can appreciate on this slide, the real-world body of evidence supports the effect of our PMOs on the trajectory of Duchenne, including an impressive 5.4-year increase in survival, a three- to four-year delay in loss of ambulation and significantly slower rates of pulmonary and cardiac decline.

請看下一張投影片。在這張投影片中，您將看到現實世界的證據如何支持 golodirsen，包括與外部控制相比，喪失行走能力延遲三年，夜間呼吸器需求延遲 7.5 年，以及死亡率降低 70%。請看下一張投影片。正如您在這張投影片上所看到的，現實世界的證據支持我們的 PMO 對杜氏肌肉營養不良症的進展軌跡的影響，包括令人印象深刻的 5.4 年生存期延長、3 至 4 年喪失行走能力延遲以及肺功能和心臟功能下降速度明顯減緩。

Next slide. Further, it's important to note that our exon skipping therapies have treated over 1,800 patients worldwide from infants to adults in their 30s, providing a robust foundation of clinical experience and real-world evidence showing PMOs have been associated with slowing Duchenne disease progression, including delayed loss of ambulation, preserved pulmonary and cardiac function and extending survival. With a patient adherence rate of more than 90%, the sustained use reflects the clinical value of our exon skippers. And we were also pleased to announce at this year's World Muscle Society meeting that a clinically meaningful attenuation of pulmonary decline was demonstrated in patients with advanced Duchenne treated with casimersen compared to matched external controls. And it's also important to note that most of our post-marketing requirements or PMRs have been completed.

下一張投影片。此外，值得注意的是，我們的外顯子跳躍療法已在全球範圍內治療了 1800 多名患者，從嬰兒到 30 多歲的成年人，這提供了強大的臨床經驗和真實世界證據基礎，表明 PMO 與減緩杜氏肌肉營養不良症的進展有關，包括延緩喪失行走能力、保持肺和心臟功能以及延長生存期。患者依從率超過 90%，持續使用反映了我們外顯子跳躍療法的臨床價值。我們也很高興地在今年的世界肌肉協會會議上宣布，與匹配的外部對照組相比，接受卡西美森治療的晚期杜氏肌肉營養不良症患者的肺功能下降得到了具有臨床意義的緩解。值得注意的是，我們的大部分上市後要求或 PMR 都已完成。

Next slide, please. In terms of next steps, with the completion of ESSENCE, we've submitted the top line results to the agency. We plan to submit a request to schedule a meeting with the division by the end of the year to review the totality of evidence and discuss the path to a traditional approval. Our findings will also be shared at future scientific forums with plans for publication in a peer-reviewed journal. I'd like to take this moment to thank the Duchenne community, clinical trial investigators and KOLs for their unwavering support these past years.

請看下一張投影片。至於下一步，隨著 ESSENCE 專案的完成，我們已將主要結果提交給了代理商。我們計劃在年底前提交一份請求，安排與該部門舉行會議，以審查所有證據並討論正式批准的途徑。我們的研究成果也將在未來的科學論壇上分享，並計劃在同行評審期刊上發表。我想藉此機會感謝杜氏肌肉營養不良症患者群體、臨床試驗研究人員和關鍵意見領袖們在過去幾年中給予的堅定支持。

Drug development often poses what can seem like unmovable obstacles. In the face of those obstacles, particularly in rare and ultra-rare disease, we remain steadfast in the science and focused on taking the best, albeit at times the more challenging path forward for the benefit of patients. We remain committed to our exon-skipping therapies and to the benefit they have provided and continues to provide to those living with Duchenne.

藥物研發常常會遇到看似無法克服的障礙。面對這些障礙，尤其是在罕見疾病和超罕見疾病領域，我們始終堅定不移地堅持科學，專注於採取最佳的、儘管有時更具挑戰性的道路，以造福患者。我們將繼續致力於外顯子跳躍療法，以及該療法已經並將繼續為杜氏肌肉營養不良症患者帶來的益處。

I'll now turn the call back to Doug.

現在我把電話轉回給道格。

Thank you, Louise. All right. Next slide, please. Let's move now to performance. Notwithstanding unprecedented disruptions in the quarter, ELEVIDYS and the PMOs together posted solid net product revenue of $370 million for the quarter.

謝謝你，路易絲。好的。請看下一張投影片。現在我們來談談性能。儘管本季遭遇了前所未有的干擾，但 ELEVIDYS 和 PMO 共同實現了本季 3.7 億美元的穩健淨產品收入。

Our Chief Commercial Officer, Patrick Moss, will provide more color on that in a moment. As to the ELEVIDYS label, we have had very productive dialogue with OTP, and we expect the label change process with FDA to be concluded very soon. Dr. Rodino-Klapac will discuss our expectations for the label very shortly, along with our planned trial for the prophylactic treatment of sirolimus.

我們的首席商務官帕特里克·莫斯稍後將對此進行更詳細的說明。關於 ELEVIDYS 的標籤，我們與 OTP 進行了非常有成效的對話，我們預計與 FDA 的標籤變更流程很快就會完成。Rodino-Klapac 博士很快就會討論我們對該標籤的預期，以及我們計劃進行的西羅莫司預防性治療試驗。

As it relates to our portfolio, we are very enthusiastic about our siRNA platform as the rest of biotech appears also to be enthused with the increasingly derisked potential of siRNA. Louise will discuss our progress on that in a bit. Finally, I would note that in the quarter, we took several important actions to strengthen our financial performance and align our resources with our strategic focus on supporting our current therapies while we advance our largely siRNA-based pipeline. Our CFO, Ryan Wong, will provide color on those actions in his remarks.

就我們的產品組合而言，我們對我們的 siRNA 平台充滿熱情，因為其他生物技術公司似乎也對 siRNA 風險日益降低的潛力感到興奮。Louise稍後會和大家討論我們在這方面的進展。最後，我想指出，在本季度，我們採取了幾項重要措施來加強我們的財務業績，並將我們的資源與我們的策略重點保持一致，即支持我們當前的療法，同時推進我們主要基於siRNA的研發管線。我們的財務長 Ryan Wong 將在演講中詳細介紹這些舉措。

And with that, I will turn the call back over to Louise again to make some remarks on ELEVIDYS and on our pipeline. Louise?

接下來，我會把電話再次交給 Louise，讓她對 ELEVIDYS 和我們的管道發表一些看法。路易絲？

Thank you, Doug. And the next slide, please. Moving now to our ELEVIDYS and pipeline updates. Next slide. To update you on the safety label process for ELEVIDYS, as previously discussed, we've agreed to a black box warning for ALI and ALF.

謝謝你，道格。請看下一張投影片。接下來是我們的 ELEVIDYS 專案和管道更新情況。下一張投影片。為了向您報告 ELEVIDYS 的安全標籤流程，正如之前討論過的，我們已經同意對 ALI 和 ALF 添加黑框警告。

Also, consistent with the action we've already taken to pause shipments to non-ambulatory patients, we've agreed with the FDA that non-ambulatory will be removed from the indication and usage section of the prescribing information. Once we have an understanding of the risk-benefit analysis for sirolimus, we will discuss with FDA if data are sufficient to resume dosing non-ambulatory patients.

此外，為了配合我們已採取的暫停向非臥床患者發貨的措施，我們已與 FDA 達成一致，將「非臥床」從處方資訊的適應症和用法部分中刪除。一旦我們對西羅莫司的風險效益分析有了更深入的了解，我們將與 FDA 討論數據是否足以恢復對非臥床患者的給藥。

Next slide, please. As you're aware, we convened an expert committee to discuss ALF and the potential of adding additional immunosuppression regimen for the non-ambulant population. Earlier this month, the committee, which consisted of numerous globally recognized, highly experienced medical specialists, including neuromuscular physicians with ELEVIDYS treatment experience, hepatologists and specialist experience in immunosuppressive therapies, shared their findings at WMS in which they analyzed and reviewed ALF safety data to identify early indicators of ALI and define populations at elevated risk for ALF. They evaluated and recommended strategies to prevent and mitigate ALI and ALF, emphasizing early risk recognition and patient stratification, a focus on intervention, clinical pathways and risk-based management, optimized clinical management approaches for ALI and ALF, including prophylactic immunosuppression and monitoring parameters.

請看下一張投影片。如您所知，我們召集了一個專家委員會來討論 ALF 以及為非臥床人群增加額外免疫抑制方案的可能性。本月初，由眾多全球公認的、經驗豐富的醫學專家組成的委員會（包括具有 ELEVIDYS 治療經驗的神經肌肉醫生、肝病學家和免疫抑制療法專家）在世界醫學學會 (WMS) 上分享了他們的研究成果，他們分析和審查了 ALF 安全性數據，以確定 ALI 的早期指標並確定 ALF 高風險人群。他們評估並建議了預防和減輕 ALI 和 ALF 的策略，強調早期風險識別和患者分層，重點關注幹預、臨床路徑和基於風險的管理，優化 ALI 和 ALF 的臨床管理方法，包括預防性免疫抑制和監測參數。

Based on these discussions and analyses, the committee endorsed modifying hepatic biomarker thresholds in ALI to facilitate timely intervention. They also recommended enhanced liver characterization of baseline to better understand risk factors of developing ALI. In terms of ALI prevention, they recommended adding prophylactic sirolimus as a second agent to the current corticosteroid regimen versus increasing corticosteroid doses, and this is one to two weeks prior to infusing ELEVIDYS. In terms of ALI management, the committee recommended prompt initiation of IV corticosteroids if patients do not respond to oral corticosteroids. Lastly, they emphasized the need to generate real-world and clinical data.

基於這些討論和分析，委員會認可修改 ALI 中的肝臟生物標記閾值，以便及時進行幹預。他們還建議加強對基線肝臟特徵的分析，以便更好地了解發生急性肝損傷的風險因素。在預防 ALI 方面，他們建議在目前的皮質類固醇治療方案中加入預防性西羅莫司作為第二種藥物，而不是增加皮質類固醇的劑量，並且這需要在輸注 ELEVIDYS 前一到兩週進行。在 ALI 管理方面，委員會建議，如果患者對口服皮質類固醇沒有反應，則應立即開始靜脈注射皮質類固醇。最後，他們強調了產生真實世界和臨床數據的必要性。

Toward that end, and as we've communicated previously, Cohort 8 of our ENDEAVOR study is designed to demonstrate the effectiveness of additional prophylactic immunosuppression in non-ambulatory patients receiving ELEVIDYS. We are in discussions with FDA about the design of the study and hope to be able to commence it soon.

為此，正如我們之前所溝通的那樣，我們的 ENDEAVOR 研究的第 8 組旨在證明對接受 ELEVIDYS 治療的非臥床患者進行額外的預防性免疫抑制的有效性。我們正在與FDA討論研究方​​案的設計，希望能盡快啟動這項研究。

Next slide, please. Also of note at this year's WMS meeting were the results of an independent study led by Dr. Jonathan Soslow from the Department of Pediatrics at Vanderbilt University Medical Center. The study included 20 Duchenne patients who received ELEVIDYS. The first 14 patients received ELEVIDYS with a standard protocol, including corticosteroids, but no additional immunosuppression.

請看下一張投影片。今年 WMS 會議上值得關注的還有范德比爾特大學醫學中心兒科系的 Jonathan Soslow 博士領導的一項獨立研究的結果。研究納入了 20 名接受 ELEVIDYS 治療的杜氏肌肉營養不良症患者。前 14 名患者接受了 ELEVIDYS 標準方案治療，包括皮質類固醇，但沒有額外的免疫抑制治療。

The six subsequent patients underwent a modified immunosuppression protocol with sirolimus. The objective was to show the initial safety, tolerability and efficacy of sirolimus prophylaxis. What the results demonstrated was that a low dose of sirolimus prophylaxis appeared to be safe and well tolerated in the Duchenne patients receiving ELEVIDYS, and there were no observed increases in liver enzymes in the six patients treated with sirolimus.

隨後的六名患者接受了改良的免疫抑制方案，使用西羅莫司。目的是證明西羅莫司預防的初步安全性、耐受性和有效性。結果表明，對於接受 ELEVIDYS 治療的杜氏肌肉營養不良症患者，低劑量西羅莫司預防似乎是安全且耐受性良好的，並且在接受西羅莫司治療的 6 名患者中未觀察到肝酶升高。

Next slide, please. Moving now to our pipeline updates. Next slide and beginning with our LGMD Type 2E program. Regarding SRP-9003 for LGMD Type 2E, we recently presented positive Phase III emerging data at the WMS meeting. The study met its primary endpoint, demonstrating a significant increase in beta-sarcoglycan expression.

請看下一張投影片。接下來是我們的管道更新情況。下一張投影片，從我們的 LGMD 2E 型程式開始。關於 SRP-9003 用於治療 LGMD 2E 型，我們最近在 WMS 會議上公佈了積極的 III 期新數據。該研究達到了主要終點，顯示β-肌聚醣表現顯著增加。

In addition, restoration of other sarcoglycan complex proteins in both ambulatory and non-ambulatory patients was demonstrated. Further, our safety and tolerability results were consistent with previous results. We are encouraged by these data to support SRP-9003's clinical benefit in patients living with LGMD Type 2E. To determine the path forward, we have scheduled a meeting with the FDA this quarter. Following this regulatory dialogue, we will assess the requirements and determine the appropriate next steps for the program.

此外，研究也證實，無論患者是能夠行走或無法行走，其他肌聚醣複合物蛋白都得到恢復。此外，我們的安全性和耐受性結果與先前的結果一致。這些數據令人鼓舞，支持 SRP-9003 對患有 LGMD 2E 型的患者俱有臨床益處。為了確定未來的發展方向，我們已安排在本季與美國食品藥物管理局 (FDA) 舉行會議。在本次監管對話之後，我們將評估相關要求，並確定該計劃的適當後續步驟。

Lastly, we turn to our promising siRNA pipeline. The recent activity in this space underscores the significant opportunity for this modality, and we are excited by our potential best-in-class approaches. Our DM1 and FSHD programs continue to advance rapidly. Enrollment is progressing well in both trials. For DM1, enrollment in the SAD study is complete and Cohort 4 of the MAD study at 6 mg per kg is currently enrolling.

最後，我們來看看我們前景廣闊的siRNA研發管線。該領域近期的活躍度凸顯了這種模式的巨大機遇，我們對我們潛在的一流方法感到興奮。我們的 DM1 和 FSHD 專案持續快速發展。兩項試驗的受試者招募工作進展順利。對於 DM1，SAD 研究的入組已完成，MAD 研究的第 4 組（6 mg/kg）目前正在入組。

For FSHD, enrollment of the SAD study is complete and Cohort 6 of the MAD study or 12 mg per kg will begin enrolling this month. While we previously expected to release single dose ascending data by the end of the year, our team is currently prioritizing the transfer and validation of assays necessary to provide high-quality PD data.

對於 FSHD，SAD 研究的入組已經完成，MAD 研究的第 6 組（每公斤 12 毫克）將於本月開始入組。雖然我們之前預計在年底前發佈單劑量遞增數據，但我們的團隊目前優先考慮轉移和驗證提供高品質 PD 數據所需的檢測方法。

As a result, we now anticipate sharing these initial results in the first quarter of 2026. We also plan to initiate our trial for Huntington's disease by the year-end. This program utilizes a subcutaneous route of administration, allowing for deep brain regions like the striatum, particularly affected by Huntington's. In addition to the second-generation DM1 candidate selected at deal close, which has the ability to cross the blood-brain barrier and address the cognitive aspects of DM1. We have also selected three of our research targets, which we plan to discuss at a later date.

因此，我們預計將於 2026 年第一季公佈這些初步結果。我們也計劃在年底前啟動亨廷頓舞蹈症的試驗。此方案採用皮下給藥途徑，可以到達大腦深處的區域，例如受亨廷頓氏症影響的紋狀體。除了在交易完成時選定的第二代 DM1 候選藥物外，該藥物能夠穿過血腦屏障並解決 DM1 的認知方面問題。我們也選定了三個研究方向，計劃在稍後進行討論。

We continue to be excited by our differentiated approaches with siRNA and look forward to updating you in 2026.

我們對採用 siRNA 的差異化方法感到興奮，並期待在 2026 年向您報告最新進展。

I'll turn the call over to Patrick Moss for an update on our commercial performance. Next slide. Patrick?

我將把電話轉給帕特里克·莫斯，請他報告我們的商業表現。下一張投影片。派崔克？

Thank you, Louise, and good afternoon, everyone. My comments today will focus on three areas; a review of our Q3 performance, my thoughts on the ESSENCE results and our expectations for the trajectory of ELEVIDYS.

謝謝你，路易絲，大家午安。我今天的發言將集中在三個方面：回顧我們第三季度的業績、我對 ESSENCE 結果的看法以及我們對 ELEVIDYS 的發展軌蹟的預期。

Next slide, please. Total product revenue for the quarter was $370 million, including $131 million in ELEVIDYS net product revenue and $239 million in PMO net product revenue. The pause in shipments to the ambulatory population, which resumed following the FDA's recommendation, created meaningful disruptions to patient access. Some infusion dates were canceled, requiring some families to reinitiate the logistical process, antibody testing, rescheduling appointments and reconfirming insurance authorization. New patient identification efforts were also delayed as a result of physicians requiring clarification on the reasons for the voluntary pause.

請看下一張投影片。本季產品總收入為 3.7 億美元，其中 ELEVIDYS 淨產品收入為 1.31 億美元，PMO 淨產品收入為 2.39 億美元。暫停向門診患者發貨，在 FDA 建議後恢復，但這對患者的就醫造成了嚴重的干擾。一些輸液日期被取消，導致一些家庭必須重新啟動後勤流程，包括抗體檢測、重新安排預約和重新確認保險授權。由於醫生要求澄清自願暫停的原因，新患者識別工作也因此被推遲。

Despite these challenges, our teams responded swiftly and decisively, working closely with sites and families to ensure continuity of care. Importantly, demand for ELEVIDYS proved resilient amongst those patients that had scheduled infusions with some infusions resuming within a week of lifting the pause on ambulatory shipments. We also continue to engage our key stakeholders, including payers. We've had productive discussions with payers since the pause and have not seen unfavorable shifts in coverage for ELEVIDYS. In the ambulatory population, approximately 220 million lives have a path to coverage.

儘管面臨這些挑戰，我們的團隊迅速果斷地做出反應，與各機構和家屬密切合作，確保照護的連續性。重要的是，對於那些已安排輸液的患者來說，ELEVIDYS 的需求表現出了韌性，一些輸液在暫停門診運輸後的一周內就恢復了。我們也將繼續與包括支付方在內的主要利害關係人保持溝通。自暫停以來，我們與支付方進行了富有成效的討論，並且沒有看到 ELEVIDYS 的承保範圍出現不利變化。在可自由活動的人群中，約有 2.2 億人有途徑獲得醫療保險。

We continue to fight for our patients and to date, we're not aware of a single permanent denial for coverage. Our PMO franchise delivered strong demand based on performance this quarter. Performance also benefited from additional shipping days in the Q3 calendar compared to the upcoming fourth quarter.

我們繼續為患者爭取權益，迄今為止，我們還沒有發現任何永久性拒保的情況。本季度，我們的專案管理辦公室（PMO）業務憑藉良好的業績，獲得了強勁的需求。與即將到來的第四季相比，第三季的出貨天數增加也對業績有所好處。

Now turning to the ESSENCE study. We look forward to connecting with physicians, patients and payers to share the data at upcoming congresses and through additional compliant channels. We believe the totality of the evidence demonstrating the value of our PMOs will be viewed by HCPs and families as proof of an innovative treatment option that can have an impact on the trajectory of the disease. Our PMOs have generated a significant amount of real-world evidence supporting the efficacy of these products. The real-world evidence, coupled with the data set from ESSENCE, only solidifies our view about the importance of these treatment options for patients living with Duchenne.

現在來看看 ESSENCE 的研究。我們期待在即將舉行的會議上以及透過其他合規管道與醫生、患者和支付方聯繫，分享數據。我們相信，所有證明我們 PMO 價值的證據，將被醫療保健專業人員和患者家屬視為一種創新治療方案的證明，該方案可以對疾病的進程產生影響。我們的專案管理辦公室已經產生了大量真實世界證據，以支持這些產品的有效性。現實世界的證據，加上 ESSENCE 的資料集，更加鞏固了我們對這些治療方案對於杜氏肌肉營養不良症患者的重要性的看法。

As evidenced by our Q3 performance, we have successfully restarted shipping for ambulatory patients, and we have begun to see new ELEVIDYS enrollment forms submitted.

從我們第三季的業績可以看出，我們已經成功恢復了門診患者的藥品配送，並且我們已經開始看到新的 ELEVIDYS 登記表提交。

However, the disruptions in the market this year, combined with the typical seasonal dynamics in Q4 will temporarily impact demand generation and the influx of new enrollment forms. Due to the resulting delays, we expect the Q4 infusion volumes to be flat to slightly down from Q3. Despite these near-term dynamics, we remain confident in the long-term opportunity for ELEVIDYS and are comfortable reiterating our guidance that the ambulant population alone represents an annual revenue opportunity with a $500 million floor. Our conviction is based on the wealth of data demonstrating the benefits of ELEVIDYS.

然而，今年的市場動盪，加上第四季的典型季節性因素，將暫時影響需求產生和新報名表的湧入。由於由此造成的延誤，我們預計第四季輸液量將與第三季持平或略有下降。儘管近期存在這些動態，但我們仍然對 ELEVIDYS 的長期發展機會充滿信心，並可以重申我們的預期，即僅可自由活動的人群就代表著每年至少 5 億美元的收入機會。我們的信念源自於大量數據，這些數據證明了 ELEVIDYS 的益處。

Further, based on our ongoing dialogue with providers, we do not anticipate the inclusion of the box warning in the final label to have a significant impact on prescribing behaviors, and our field teams are fully equipped to support informed conversations with all stakeholders. The data continues to reinforce this long-term view. We are energized by the reception to our data presentations at this year's World Muscle Society, in particular, the three-year functional outcomes data for ELEVIDYS has resonated strongly with health care providers, reinforcing the durability of benefit and the therapy's potential to slow disease progression. Now to remind everyone, we have now treated greater than 1,100 patients with ELEVIDYS in both the clinical and commercial setting, providing patients with an effective therapy that is designed to impact the trajectory of their disease.

此外，根據我們與供應商的持續對話，我們預計在最終標籤中加入黑框警告不會對處方行為產生重大影響，我們的現場團隊已做好充分準備，支持與所有利益相關者進行知情對話。數據持續印證了這個長期觀點。我們對今年世界肌肉協會的數據展示所獲得的反響感到振奮，特別是ELEVIDYS的三年功能結果數據引起了醫療保健提供者的強烈共鳴，這進一步證實了療效的持久性和該療法減緩疾病進展的潛力。現在提醒大家，我們在臨床和商業環境中已經用 ELEVIDYS 治療了 1100 多名患者，為患者提供了一種旨在影響其疾病軌蹟的有效療法。

Taken together, these results underscore the strength of our portfolio and the resilience of our commercial execution. This team has led an incredible launch through undoubtedly turbulent times, and I have the conviction that this team will continue to deliver results. We remain deeply committed to supporting patients and families, and we are confident in our ability to navigate the near-term dynamics while advancing our mission to transform the lives of those living with this devastating disease. As I continue to meet with HCPs and hear family stories, I am moved by how our therapies are having a positive impact on the lives of patients living with Duchenne.

綜合來看，這些結果凸顯了我們產品組合的實力和我們商業執行的韌性。這個團隊在充滿挑戰的時期成功完成了令人難以置信的產品發布，我相信這個團隊將繼續取得佳績。我們始終堅定地致力於支持患者及其家人，並且我們有信心應對近期的各種挑戰，同時推進我們的使命，改變那些患有這種毀滅性疾病的人們的生活。隨著我不斷與醫療保健專業人員會面並聆聽患者家屬的故事，我深受感動，因為我們的療法正在對杜氏肌肉營養不良症患者的生活產生積極影響。

I'll now turn the call over to Ryan Wong to discuss financial results. Ryan?

現在我將把電話交給 Ryan Wong，讓他討論財務表現。瑞恩？

Thank you, Patrick, and good afternoon, everyone. This afternoon's press release provided details for the third quarter of 2025 on a GAAP basis as well as a non-GAAP basis. Please refer to the press release available on Sarepta's website for a full reconciliation of GAAP to non-GAAP financial results.

謝謝你，派崔克，大家下午好。今天下午的新聞稿提供了 2025 年第三季的詳細數據，包括 GAAP 準則和非 GAAP 準則下的數據。有關 GAAP 與非 GAAP 財務結果的完整調整表，請參閱 Sarepta 網站上提供的新聞稿。

Next slide, please. I'd like to start my remarks today by thanking the Sarepta team for their commitment and diligence as we executed well against the revised strategy and refocused pipeline that we announced in July. Importantly, we took proactive steps in the third quarter to enhance our near-term liquidity and to improve our balance sheet and debt profile. We monetized strategic investments, completed a debt exchange, which reduced maturities due in 2027 from $1.15 billion to $450 million and significantly reduced our go-forward cost structure. In Q3, we were cash flow positive.

請看下一張投影片。今天，我首先要感謝 Sarepta 團隊的奉獻和勤奮，感謝他們為我們成功執行 7 月宣布的修訂策略和重新聚焦的產品線所付出的努力。重要的是，我們在第三季採取了積極措施，以增強我們的近期流動性，並改善我們的資產負債表和債務狀況。我們實現了戰略投資的貨幣化，完成了債務置換，將 2027 年到期的債務從 11.5 億美元減少到 4.5 億美元，並大幅降低了未來的成本結構。第三季度，我們實現了正現金流。

Cash and investments increased from $850 million to $865 million. And from the strengthened financial foundation, we will continue to advance our pipeline and strategy.

現金和投資從 8.5 億美元增加到 8.65 億美元。憑藉更穩固的財務基礎，我們將繼續推進我們的產品線和策略。

I will now touch on the key highlights from our third quarter financial results. Next slide, please. Total revenues were $399 million in the quarter, which consisted of $370 million in net product revenues and $29 million of collaboration and other revenues, which relates to contract manufacturing and royalty income from our partnership with Roche. Q3 cost of sales totaled $151 million, up from $92 million in the same quarter prior year. The increase reflects higher ELEVIDYS cost of goods due to depletion of previously expensed inventory and increased failed batch costs.

接下來，我將重點介紹我們第三季財務業績的幾個關鍵亮點。請看下一張投影片。本季總收入為 3.99 億美元，其中包括 3.7 億美元的淨產品收入和 2,900 萬美元的合作及其他收入，後者與合約製造和我們與羅氏合作的特許權使用費收入有關。第三季銷售成本總計 1.51 億美元，高於去年同期的 9,200 萬美元。此次成長反映了由於先前計入費用的庫存消耗和失敗批次成本增加，ELEVIDYS 的商品成本上升。

Additionally, we recorded $22 million in charges for write-offs of deposits tied to certain ELEVIDYS manufacturing suites and take-or-pay shortfall payments.

此外，我們還提列了 2,200 萬美元的費用，用於沖銷與某些 ELEVIDYS 生產套件相關的押金和照付不議的差額付款。

Following the pause in shipping to the non-ambulatory population, we acted quickly with our strategic manufacturing partner to align ELEVIDYS production with near-term demand. As a result, we have deferred manufacturing commitments and payments from the first half of 2026 to 2027, while maintaining what we expect to be sufficient inventory to meet global demand.

在暫停向行動不便人群發貨後，我們與戰略製造合作夥伴迅速採取行動，使 ELEVIDYS 的生產與近期需求保持一致。因此，我們將 2026 年上半年的生產承諾和付款推遲到 2027 年，同時保持我們預計足以滿足全球需求的庫存。

Moving on to expenses. Let me start with the restructuring charge reported in Q3. Following our July business and strategy update, which included a reduction in force and reprioritization of our pipeline, we incurred $41 million in restructuring costs, of which $35 million related to severance and other onetime termination benefits and the remainder related to the accelerated depreciation of certain impacted assets.

接下來是費用部分。首先，我想談談第三季報告的重組費用。繼我們 7 月的業務和策略更新（包括裁員和重新調整專案優先事項）之後，我們產生了 4,100 萬美元的重組成本，其中 3,500 萬美元與遣散費和其他一次性終止福利有關，其餘部分與某些受影響資產的加速折舊有關。

Moving next to R&D. In the third quarter, GAAP R&D expenses were $219 million and non-GAAP R&D expenses were $207 million, both essentially flat to prior year. Nearly half of our reported R&D expense relates to the $100 million milestone paid to Arrowhead for meeting certain enrollment and safety thresholds in our SRP-1003 DM1 program.

接下來進入研發階段。第三季度，GAAP研發費用為2.19億美元，非GAAP研發費用為2.07億美元，兩者皆與去年基本持平。在我們報告的研發費用中，近一半與支付給 Arrowhead 的 1 億美元里程碑款項有關，該款項用於表彰我們在 SRP-1003 DM1 項目中達到一定的招募和安全門檻。

Turning to SG&A. We reported $92 million and $77 million on a GAAP and non-GAAP basis, respectively, representing a year-over-year decrease of 28% and 23%, respectively. These decreases were driven by lower compensation expenses as well as lower commercial spend following our cost restructuring efforts. Looking ahead to the remainder of the year, we expect combined non-GAAP R&D and SG&A expenses of approximately $420 million to $430 million in the fourth quarter. This includes $200 million payable to Arrowhead for the second DM1 milestone, which we anticipate recording in Q4 with payment due in the first quarter of 2026.

接下來是銷售、一般及行政費用。我們分別以 GAAP 和非 GAAP 準則報告了 9,200 萬美元和 7,700 萬美元的收入，年比分別下降了 28% 和 23%。這些下降是由於成本重組措施後，薪資支出和商業支出減少所致。展望今年剩餘時間，我們預期第四季非GAAP研發及銷售、管理及行政費用總計約為4.2億美元至4.3億美元。其中包括向 Arrowhead 支付的 2 億美元，作為 DM1 第二個里程碑的款項，我們預計將在第四季度確認該里程碑，款項將於 2026 年第一季支付。

For the full year, our guidance for combined non-GAAP R&D and SG&A expenses is approximately $1.86 billion. Excluding the Arrowhead transaction costs and DM1 milestones together totaling $884 million, our underlying expense guidance is roughly $976 million. Recall, our 2025 guidance prior to our July business and strategy update was between $1.2 billion and $1.3 billion, which means we have reduced planned expenses by nearly $300 million from the midpoint. This reflects our commitment to disciplined capital allocation, and we remain on track to meet our restructuring targets into next year.

我們對全年非GAAP研發及銷售、管理及行政費用的預期約為18.6億美元。不計入 Arrowhead 交易成本和 DM1 里程碑付款（總計 8.84 億美元），我們的基本支出預期約為 9.76 億美元。回顧一下，在我們 7 月的業務和策略更新之前，我們對 2025 年的預期是 12 億美元至 13 億美元，這意味著我們已將計畫支出從中間值減少了近 3 億美元。這反映了我們對嚴格資本配置的承諾，我們仍有望在明年實現重組目標。

Lastly, in Q3, we reported an operating loss of $103 million and $36 million on a GAAP and a non-GAAP basis, respectively. Adjusting for the $41 million restructuring charge and the $100 million DM1 milestone, our underlying business would have reported a GAAP and non-GAAP operating profit of $37 million and $54 million, respectively. Additionally, adjusting for the $584 million Arrowhead upfront transaction cost, our underlying business has delivered a robust year-to-date GAAP and non-GAAP operating profit of $436 million and $561 million, respectively. In closing, with our financial performance and the actions we took in the quarter to strengthen our financial foundation, we believe we are well positioned to execute our strategy and meet our financial obligations even under revenue stress test scenarios. Looking ahead, our capital allocation priorities remain focused on investments that drive demand for our on-market therapies and advance our SNA platform towards potential near-term value inflection points.

最後，在第三季度，我們分別按美國通用會計準則和非美國通用會計準則報告了 1.03 億美元的營業虧損和 3,600 萬美元的營業虧損。扣除 4,100 萬美元的重組費用和 1 億美元的 DM1 里程碑付款後，我們的基礎業務將分別報告 GAAP 和非 GAAP 營業利潤 3,700 萬美元和 5,400 萬美元。此外，在扣除 5.84 億美元的 Arrowhead 預付交易成本後，我們的基礎業務今年迄今分別實現了 4.36 億美元和非 GAAP 營業利潤，表現強勁。總之，憑藉我們的財務表現以及本季度為加強財務基礎而採取的措施，我們相信，即使在收入壓力測試情境下，我們也能夠很好地執行我們的策略並履行我們的財務義務。展望未來，我們的資本配置重點仍然是投資於能夠推動市場對我們現有療法的需求，並推動我們的 SNA 平台朝著潛在的近期價值轉折點邁進的投資。

And now I'll turn the call back to Doug for closing remarks. Doug?

現在我把電話轉回給道格，請他作總結發言。道格？

Thank you, Ryan. Let's open the call for questions, and then I'll make some closing remarks.

謝謝你，瑞恩。現在開始接受提問，之後我將作總結發言。

Thank you. We will now begin the question-and-answer session. (Operator Instructions)

謝謝。現在開始問答環節。（操作說明）

Anupam Rama, JPMorgan.

Anupam Rama，摩根大通。

Hey guys, thanks so much for taking the question. I had just a quick question on ESSENCE. You guys talked a lot about some of the additional analyses and the COVID impact here. What other endpoints should we be looking for in a publication and/or medical conference presentation, FDA package that you think that would be supportive of some of the data that you presented here today?

各位，非常感謝你們回答這個問題。我有一個關於ESSENCE的小問題。你們在這裡詳細討論了一些額外的分析以及新冠疫情的影響。在出版物和/或醫學會議報告、FDA申請資料中，我們還應該尋找哪些其他終點指標，以支持您今天在這裡展示的一些數據？

Yeah, thank you for that question. I will turn this to Luis.

是的，謝謝你的提問。我會把這件事轉交給路易斯。

Yes. Thanks for the question. So first, we'll be looking at the totality of evidence. So ESSENCE will be one part of that. But as we mentioned, the real-world evidence data is significant over many, many years and showing a benefit.

是的。謝謝你的提問。首先，我們將審視所有證據。所以精華部分將是其中的一部分。但正如我們所提到的，現實世界的證據數據經過很多很多年，顯示出了益處，而且意義重大。

In terms of ESSENCE, this is the top line. We have other secondary endpoints that include functional endpoints and also biological endpoints like expression, which are not complete yet. So all of that will be in the final CSR will be presented to the agency, and then that will be presented in a medical meeting. But as I mentioned in my remarks, the primary and secondaries favored the PMOs. And in terms of COVID, we saw the similar result that we saw with the primary, in which case you saw improvement with those endpoints when you looked at the COVID-free population.

就本質而言，這是最重要的一點。我們還有其他次要終點，包括功能終點和生物學終點（如表達），這些終點尚未完成。所以所有這些內容都將包含在最終的CSR報告中，並提交給監管機構，然後報告將在醫學會議上進行報告。但正如我在發言中提到的，主要選民和次要選民都支持總理辦公室。就 COVID 而言，我們看到了與主要結果類似的情況，即在觀察未感染 COVID 的人群時，這些終點指標有所改善。

Gina Wang, Barclays.

吉娜·王，巴克萊銀行。

Thank you for taking my questions. Maybe I'll just follow up regarding the COVID-free population. When we look at the p-value, it is still relatively high. It's 0.09. So like how do you think the FDA will look at the data sets here? And what could be the potential outcome with the FDA decision?

謝謝您回答我的問題。或許我應該跟進一下關於無新冠病毒感染族群的情況。從 p 值來看，它仍然相對較高。數值是0.09。那你認為FDA會如何看待這裡的數據集呢？FDA的決定可能帶來什麼後果？

One could be full approval? Should we also be worried about the drug could be pulled off the market as a potential worst-case scenario?

其中一種可能是完全批准？我們是否也應該擔心，這種藥物可能會被撤出市場，這被認為是潛在的最壞情況？

Thank you for the question, Gena. I'll make a couple of comments, and then I'll turn it to Louise. First of all, 0.09, I know that the standard is typically 0.05. Interesting enough, FDA leadership very recently noted with respect to rare diseases that 0.05 is relatively arbitrary and actually cited 0.09 as being potentially acceptable p-value. It says that 91% of the time, you're seeing a drug effect, particularly for rare disease.

謝謝你的提問，吉娜。我先說幾點，然後把麥克風交給路易絲。首先，0.09，我知道標準通常是 0.05。有趣的是，FDA 領導層最近在談到罕見疾病時指出，0.05 相對來說是任意的，並實際上將 0.09 列為可能可接受的 p 值。報告稱，91% 的情況下，你會看到藥物的效果，尤其是對於罕見疾病而言。

But I would also note that one of the reasons that we're seeing a p-value of 0.09, and we're not seeing a p-value closer to or better than 0.05 is that while 168 patients are included in the analysis here, 57 patients were excluded because they were -- their results were affected by the pandemic. And of course, that lowers the powering of the study substantially.

但我還想指出，我們看到的 p 值為 0.09，而沒有看到接近或優於 0.05 的 p 值，其中一個原因是，雖然這裡分析包含了 168 名患者，但有 57 名患者被排除在外，因為他們的結果受到了疫情的影響。當然，這會大大降低研究的效力。

So I think in light of the fact that we had to significantly lower the powering of the study to look at 168 versus for the additional 57 we would have otherwise seen, I think 0.09 is pretty darn impressive. And the effect, of course, not just the statistical significance of 0.09, but the effect is really important as we were showing a reduction in decline of 30%, which over the long run will be very, very important to these families.

所以，考慮到我們必須大幅降低研究的統計效力來觀察 168 個病例，而不是原本可以觀察到的 57 個病例，我認為 0.09 的結果相當令人印象深刻。當然，其效果不僅僅是 0.09 的統計顯著性，而且效果真的非常重要，因為我們顯示下降幅度減少了 30%，從長遠來看，這對這些家庭來說將非常非常重要。

And one of the nice things about having these therapies commercially available for so long is that we get to see what happens over the long term, as you saw with respect to just one example of many VYONDYS, you look at that for six years, and these kids are seeing literally almost three years of delay in being in a wheelchair and the time to ventilation is significantly different.

這些療法能夠長期商業化應用的好處之一是，我們可以看到長期效果。正如你從眾多 VYONDYS 療法中的一個例子中看到的那樣，觀察六年，這些孩子使用輪椅的時間實際上推遲了近三年，而且使用呼吸機的時間也明顯不同。

So I think the outcomes are a couple fold when we talk to the FDA. I really do not believe that there's a risk of losing marketing authorization, it would make very little sense given both the benefits we've seen with this therapy and considering this extraordinarily beneficial safety profile that we've seen over many years and when considering the standard that the FDA was very specific with us about as they approved VYONDYS in particular, and they were talking to ESSENCE and they said, the standard is you will be -- you will commit to voluntarily withdrawing marketing authorization, but only in a scenario where no relevant analyses would confirm a clinical benefit. Of course, we don't have that between the real-world evidence and the evidence we see here. So that -- I don't really think that is in the cards in the rational world.

所以我覺得，當我們和FDA溝通時，結果會有兩方面。我真的不認為有失去上市許可的風險，考慮到我們已經看到的這種療法的益處，以及多年來我們所看到的極其良好的安全性，再加上FDA在批准VYONDYS時向我們提出的非常具體的標準，失去上市許可就顯得毫無意義。他們當時與ESSENCE雜誌交談時說，標準是你們必須承諾自願撤回上市許可，但前提是沒有任何相關分析可以證實其具有臨床益處。當然，現實世界的證據和我們在這裡看到的證據之間並沒有必然關聯。所以——我真的不認為這會在理性世界裡發生。

And then the real question is, can we transition this therapy from an accelerated approval to a traditional approval. We certainly think we have a good argument around that. We've been spending an enormous amount of time gathering data that supports this, and we think it would be the most efficient approach, but that will require discussions with the agency, and I can't make a prediction on that in advance of having good solid discussions and review of data with the agency. Now I said, Louise, I'm going to turn it over to you, and I will do that, but I did go on a bit of a monologue there.

那麼真正的問題是，我們能否將這種療法從加速審批過渡到傳統審批。我們認為我們在這方面確實有充分的論點。我們花了大量時間收集數據來支持這一觀點，我們認為這將是最有效的方法，但這需要與相關機構進行討論，在與相關機構進行充分的討論和數據審查之前，我無法對此做出預測。我說：「路易絲，我要把事情交給你了。」我也會這麼做，但我剛才確實說了些獨白。

Yeah, I think you covered it well on there. Thank you.

是的，我覺得你講得很詳細。謝謝。

Tazeen Ahmad, Bank of America.

塔津·艾哈邁德，美國銀行。

Hi, guys. Good evening. Thanks for taking my question. Mine is on the upcoming Arrowhead data. I wanted to get a sense of what level of data to expect from these early programs that you're looking at. Importantly, these indications, DM1, FSHD, et cetera, are ones that other companies are pursuing. Can you give us a sense of what level of data to expect so that we can potentially start to compare and contrast with the other programs that are ahead of you in development? Thanks.

嗨，大家好。晚安.謝謝您回答我的問題。我的版本在即將發布的 Arrowhead 數據中。我想了解一下，你們正在研究的這些早期項目能夠提供什麼樣的數據水平。重要的是，這些適應症，如 DM1、FSHD 等，也是其他公司正在研究的適應症。您能否大致說明一下我們可以預期獲得多少數據，以便我們能夠開始與那些在開發階段領先於您的其他專案進行比較和對比？謝謝。

Yeah, I'll turn it to Louise.

好的，我把它轉給路易絲。

Sure. Well, of course, so we'll be sharing data with a single ascending dose study, and we'll be looking at safety and then we'll also have safety data for the multiple ascending dose by that time. So we'll have PK data, that's serum PK, muscle PK. And then as I mentioned in my remarks, we are working to validate and transfer the assays, the PD assays. And so that is knockdown for DM1 and looking at splicing.

當然。當然，我們會分享單次遞增劑量研究的數據，我們會研究安全性，到那時我們也會獲得多次遞增劑量研究的安全性數據。所以我們會得到 PK 數據，包括血清 PK 和肌肉 PK。正如我在演講中提到的，我們正在努力驗證和轉移這些檢測方法，即PD檢測方法。所以，DM1 的擊倒情況以及剪接情況都已查明。

And then for FSHD, we're obviously looking at downstream FSHD gene. So these are assays that we want to validate and have through, through our pivotal studies. And so we're working hard to make sure that these are in a good place so that we -- when we present our PD data, can be carried through throughout our studies. So we're excited to see this result and present it to you early next year.

至於 FSHD，我們顯然是在研究下游的 FSHD 基因。所以，這些是我們希望透過關鍵研究來驗證和驗證的檢測方法。因此，我們正在努力確保這些都處於良好狀態，以便我們在展示 PD 數據時，能夠貫穿我們的整個研究。所以我們很高興看到這個結果，並計劃在明年初向大家展示。

Brian Abrahams, RBC Capital Markets.

Brian Abrahams，加拿大皇家銀行資本市場。

Hi, this is Kevin on for Brian. Thank you for taking our questions. So we just had a couple on the proposed sirolimus study. Maybe can you just provide a little bit more color on any key sort of trial design features left to discuss there with the agency, how confident you are in the protocol that you've previously presented? And what if anything could be tweaked there? And would you still anticipate a potential readout in the first half of next year for that study? Thank you very much.

大家好，我是凱文，替布萊恩報到。感謝您回答我們的問題。所以我們剛剛就擬議的西羅莫司研究進行了幾次討論。您能否再詳細說明還有哪些關鍵的試驗設計特徵需要與監管機構討論，以及您對先前提出的方案有多大信心？如果那裡有什麼可以調整的地方呢？您是否仍預期研究的結果會在明年上半年公佈？非常感謝。

Sure. Louise?

當然。路易絲？

Sure. I think in a general sense, the protocol design is -- will be similar to what we presented. We haven't finalized it with the agency. But in general, in terms of the numbers of patients and the protocol for sirolimus, that hasn't changed. So it's been minor back and forth on the protocol itself.

當然。我認為從總體上看，協議設計將與我們提出的方案類似。我們還沒有和代理機構最終敲定此事。但總的來說，就患者人數和西羅莫司治療方案而言，情況並沒有改變。所以，協議本身只是經過了一些小小的反覆討論。

So as soon as we get that study started, we are ready to enroll quickly. Patients are lined up. And so by -- as you mentioned, in the first half of next year, we'll start to have data on the effectiveness and then in the second half of the year is when we'll have the full data set for the trial based on starting the trial soon. So we're hoping to get that initiated in the near term.

所以一旦研究開始，我們就能迅速招募受試者。病人排起了長隊。因此，正如您所提到的，明年上半年我們將開始獲得有關有效性的數據，然後在下半年，我們將根據即將開始的試驗獲得完整的試驗數據集。所以我們希望能在近期內啟動這項工作。

Joe Schwartz, Leerink Partners.

Joe Schwartz，Leerink Partners。

Great. Thanks very much. Previously, I think you mentioned that there were around 75 infusion centers around the US that were up and running, although to different degrees. So I was wondering how many are active once again after the pause? And how much variance is there across these centers in terms of the numbers of patients they're treating with ELEVIDYS now?

偉大的。非常感謝。之前，我想你提到美國大約有 75 個輸液中心正在運營，儘管運營程度各不相同。所以我想知道，暫停結束後，有多少人重新活躍了？這些中心目前使用 ELEVIDYS 治療的患者人數差異有多大？

Patrick, you can take this one.

派崔克，這關交給你了。

Sure. Well, when we look at the top sites, they continue to treat. Now those less experienced sites. During the pause, they want to understand really the information that caused us to pause. But what we've seen now is the majority of those sites are also starting to submit enrollment forms as well.

當然。嗯，當我們查看排名靠前的網站時，他們仍在繼續治療。現在說說那些經驗不足的網站。在停頓期間，他們想真正了解導致我們停頓的訊息。但我們現在看到的是，這些網站中的大多數也開始提交報名表了。

Andrew Tsai, Jefferies.

Andrew Tsai，傑富瑞集團。

Hey, thanks for taking my questions. I appreciate the update. So going back to the PMO franchise, can you remind us when the MISSION data is for EXONDYS 51 and how you would define success or failure in that study since I believe it's a dose response study, so there's no placebo arm. Thank you.

嘿，謝謝你回答我的問題。感謝您的更新。回到 PMO 系列，您能否提醒我們 MISSION 數據是針對 EXONDYS 51 的，以及您會如何定義該研究的成功或失敗，因為我相信這是一項劑量反應研究，所以沒有安慰劑組。謝謝。

Yes. Thank you very much. So that's a really interesting nuance. And Louise, you're going to correct me. I believe the readout date for MISSION is 2026.

是的。非常感謝。這是一個非常有趣的細微差別。路易絲，你得糾正我。我認為 MISSION 的最終結果公佈日期是 2026 年。

So to your very good point, MISSION is a post-marketing commitment that we have with respect to EXONDYS, but unlike ESSENCE and unlike VYONDYS and AMONDYS, it is not a confirmatory study. So there is no confirmatory study for EXONDYS and that was purposeful. The FDA in some of their memos indicated that what they really wanted to see was not a confirmation study, but rather a dose-ranging study. So there's -- essentially, it's dose ranging between 30 mg per kg, 100 mg per kg, even up to 200 mg per kg. And so the result of that is really a dose.

所以，正如您所說，MISSION 是我們對 EXONDYS 所做的上市後承諾，但與 ESSENCE 以及 VYONDYS 和 AMONDYS 不同，它不是驗證性研究。所以 EXONDYS 沒有進行驗證性研究，這是有意為之。美國食品藥物管理局 (FDA) 在一些備忘錄中表示，他們真正想看到的不是一項驗證性研究，而是一項劑量範圍研究。所以，劑量範圍基本上是每公斤 30 毫克、每公斤 100 毫克，甚至高達每公斤 200 毫克。因此，其結果實際上是一個劑量。

Is 30 mg per kg the optimal dose or is 100 mg per kg the optimal dose? So that's the consequence of that study. It's not a confirmatory study, and that will read out in 2026, and we'll go from there.

每公斤體重 30 毫克是最佳劑量，還是每公斤體重 100 毫克是最佳劑量？這就是那項研究得出的結論。這不是一項驗證性研究，驗證性研究的結果要到 2026 年才會公佈，到那時我們再做打算。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

Thanks for taking our question. This is Tommie on for Salveen. Just wondering about guidance, if there's anything that you can say on full year for ELEVIDYS and about the stress tests that you've done in the past with the $900 million PMO, $500 million ELEVIDYS. And separately, just on ESSENCE, in the context of recent events, we're just wondering if your confidence that the FDA won't move the goalpost here. Thank you.

感謝您回答我們的問題。這是湯米為薩爾文報道。想了解一下指導意見，您能否就 ELEVIDYS 的全年業績以及您過去對 9 億美元 PMO 和 5 億美元 ELEVIDYS 進行的壓力測試發表一些看法？另外，就 ESSENCE 雜誌而言，鑑於最近發生的事件，我們只是想知道您是否有信心 FDA 不會改變這裡的標準。謝謝。

I'm sorry. What was the last question? Move the goalpost for?

對不起。最後一個問題是什麼？改變目標？

For ESSENCE.

為了精華。

Yes. I feel confident based on the fact that it was in writing. The standard that we were given was in writing. In fact, we had to commit back to them in writing that, that would be the standard. It did not come from a reviewer.

是的。因為它是有書面記錄的，所以我感到很放心。我們得到的標準是有書面形式的。事實上，我們必須以書面形式向他們承諾，這將是標準。它並非來自評論員。

It came from, in the first instance, the head of the neuro division and then it was cited by the supervisor for over neuro. So I think this was a very well-established standard that we have. Plus the fact is that these therapies have been on the market for a number of years. We have extraordinary real-world evidence on their use.

最初是由神經科主任提出的，然後是神經科主管引用的。所以我認為這是我們一直以來奉行的一個非常成熟的標準。此外，這些療法已經上市多年了。我們擁有大量關於它們使用的真實世界證據。

As I think we mentioned before, this is one of the most onerous protocols for a therapy, you could imagine for commercial therapy, these young men and boys have to be infused on a weekly basis and yet families in recognition of the benefits they're seeing are -- have a compliance rate year over year over year that's greater than 90% commercially and the safety profile for these therapies is just -- is exceptional, I think, would be the fair way to say it. So I don't imagine that there'd be any reason why the division would want to change its standard. It would seem to be unnecessary.

正如我們之前提到的，這是你能想像到的商業療法中最繁瑣的治療方案之一，這些年輕男性和男孩必須每週接受輸液，然而，由於認識到他們所看到的益處，這些療法的依從率年復一年地保持在 90% 以上，而且這些療法的安全性也非常好，我認為這樣說比較公平。所以我認為該部門沒有任何理由要改變其標準。這似乎沒有必要。

As it relates to guidance, we're not in a place to give broad guidance right now, but we feel on the stress test concept, we continue to feel comfortable on that stress test we talked about. That is not our guidance for next year. We're going to come together on that. I'm looking at Patrick when I say that. But we're -- we certainly feel very comfortable about that kind of baseline concept of $500 million for ELEVIDYS.

至於指導方面，我們現在還無法給出廣泛的指導，但就壓力測試的概念而言，我們仍然對我們之前討論過的壓力測試感到放心。那不是我們明年的指導方針。我們將就此達成共識。我這麼說的時候是在看著派崔克。但我們——我們當然對 ELEVIDYS 5 億美元的基準概念感到非常滿意。

Anything else you want to say about that for the rest of the year, Patrick?

派崔克，關於這件事，你今年還有什麼想說的嗎？

Nothing new to add.

沒有什麼新內容要補充。

Thank you.

謝謝。

Gil Blum, Needham & Company.

吉爾布魯姆，尼德姆公司。

Good afternoon, and thanks for taking our question. So when should we expect to receive data from -- expression data from patients receiving prophylactic sirolimus? And would any be provided from the [ISD] that was conducted separately? Thank you.

下午好，感謝您回答我們的問題。那麼我們應該何時才能收到來自接受預防性西羅莫司治療的患者的表達數據呢？單獨進行的[ISD]是否會提供任何結果？謝謝。

Louise?

路易絲？

The expression data would -- assuming the study started soon would be late next year just in terms of saying the biopsies and analyzing them. In the study that Dr. Soslow conducted, biopsies were not part of that. I think that is something that he's looking at, but that was not part of the original study design.

假設研究很快開始，僅就活檢和分析而言，表達數據就要到明年年底才能獲得。在索斯洛博士進行的研究中，活檢並不包含在內。我認為他正在研究這個問題，但這不是最初研究設計的一部分。

I think that it's a very good question and a very interesting one. The primary reason that we're looking at the use of prophylactic sirolimus is the evidence we have preclinically and some of the early clinical data that it will greatly enhance the safety profile of this therapy, particularly for non-ambulatory patients.

我認為這是一個非常好的問題，也是一個非常有趣的問題。我們考慮使用預防性西羅莫司的主要原因是，我們在臨床前研究和一些早期臨床數據中發現，這將大大提高該療法的安全性，特別是對於無法行走的患者。

But one of the things we've seen preclinical, we have not seen clinically yet because we have -- no one's taken -- performed a biopsy yet.

但我們在臨床前研究中觀察到的現象，尚未在臨床研究中觀察到，因為還沒有人進行切片檢查。

But preclinically, we've seen the opportunity to potentially greatly enhance expression, which in turn may significantly enhance benefit and durability and the like. So we're very interested in seeing in addition to the safety issue, which is without a doubt the primary reason for conducting this study, seeing some of that expression data as well, and that will be a next year event.

但在臨床前研究中，我們看到了大幅增強表達的潛在機會，這反過來可能會顯著增強療效和持久性等。因此，除了安全問題（這無疑是進行這項研究的主要原因）之外，我們也非常有興趣了解一些表達數據，這將是明年發生的事情。

Yanan Zhu, Wells Fargo.

朱亞楠，富國銀行。

Great. Thanks for taking our questions. Just maybe a quick follow-up to a prior question. To what degree does FDA's reaction to ESSENCE spill over, for example, to EXONDYS 51? Is there a possibility that the decision or reaction positive or negative, is there a mechanism for it to also apply to 51 because there's no formal 51 confirmatory studies? And also wanted to -- curious, in your mind, what is the relevance of the precedent of NS Pharma, their confirmatory trial and that outcome, whether that has any implication to your situation? Thank you.

偉大的。謝謝您回答我們的問題。或許可以快速補充一下之前的問題。例如，FDA 對 ESSENCE 的反應在多大程度上會影響到 EXONDYS 51？是否有可能，如果該決定或反應是肯定的或否定的，是否有某種機制使其也適用於 51，因為沒有正式的 51 項驗證性研究？另外，我還想問——我很好奇，您認為NS Pharma的先例、他們的驗證性試驗及其結果與您的情況有何關聯？這是否對您的情況有任何影響？謝謝。

I think the only thing I'd say about NS Pharma, and we don't know a ton about the details other than I think it's certainly proof that this division is being rational and isn't being excessively punitive for those who may not know, NS Pharma had a study for a PMO. That study did not hit stat sig, I think there were some reasons for that. And I think the division has been quite thoughtful about that. And that happened some time ago, and they certainly don't seem to be moving to do anything irrational. To your first question, the question is an interesting one.

關於 NS Pharma，我唯一想說的是，我們對細節了解不多，但我認為這肯定證明了該部門是理性的，並沒有過度懲罰那些可能不知道的人，NS Pharma 曾為一家 PMO 公司做過研究。我認為那項研究沒有達到統計學顯著性，原因可能有以下幾點。我認為該部門在這方面考慮得相當周全。這件事已經過去一段時間了，而且他們現在看起來肯定不會做出任何不理智的事情。你的第一個問題很有意思。

Do you think the outcome of ESSENCE has some read-through in some way to EXONDYS? And the short answer is, no. It does either positive or negative.

你認為 ESSENCE 的結果會在某種程度上對 EXONDYS 產生影響嗎？簡而言之，答案是否定的。它既可以產生正面影響，也可以產生負面影響。

I don't think it gives us a great mechanism to immediately make EXONDYS traditional approval if we're able to get traditional approval for VYONDYS and AMONDYS. And likewise, I don't think it has any other negative read-through to EXONDYS at all for the simple reason that the ESSENCE is specifically for two therapies, VYONDYS and AMONDYS that we're in that study and EXONDYS doesn't have that kind of study.

我不認為如果我們能夠獲得 VYONDYS 和 AMONDYS 的傳統批准，就能立即獲得 EXONDYS 的傳統批准。同樣地，我認為它對 EXONDYS 沒有任何負面影響，原因很簡單，ESSENCE 專門針對我們正在進行研究的兩種療法 VYONDYS 和 AMONDYS，而 EXONDYS 則沒有進行此類研究。

Again, EXONDYS was approved with a post-marketing commitment to look at dose ranging. We'll have an opportunity to talk about transitioning to a traditional approval with EXONDYS, but only after we've completed our post-marketing commitment to look at that dose-ranging study of the 30, 100 and even up to 200 and then look at the benefits of that versus the downsides of extra dosing and the time it takes to infuse. So we'll look at all of that, and that will be its pathway to a traditional approval if things go well there.

同樣，EXONDYS 獲準上市後，承諾會研究劑量範圍。我們將有機會討論將 EXONDYS 過渡到傳統審批流程，但前提是我們必須完成上市後研究，研究劑量範圍（30、100 甚至高達 200 毫克）的試驗，然後權衡其益處與額外給藥和輸注所需時間的弊端。所以我們會考慮所有這些因素，如果一切順利，這將是它獲得傳統批准的途徑。

But ESSENCE doesn't never read through there as far as we can see logically.

但就我們目前的邏輯理解來看，《精華》這本書似乎並沒有真正理解這一點。

Mike Ohls, Morgan Stanley.

麥克‧奧爾斯，摩根士丹利。

Good afternoon. Thanks for taking the question. Maybe just a follow-up on ESSENCE in terms of time lines here. When could you potentially meet with the FDA? And when would you expect to roughly have a final decision on that -- on the PMO franchise? Thanks.

午安.感謝您回答這個問題。或許這裡只需要對 ESSENCE 的時間線做一個後續說明。您大概什麼時候可以和FDA會面？那麼，您預計何時能就專案管理辦公室（PMO）特許經營權做出最終決定？謝謝。

Louise, do you want to take that?

路易絲，你想拿那個嗎？

Sure. So the meeting request will go in by the end of the year. So the meeting will take place sometime in the first quarter based on that request. And so then later in the spring, the final CSR will be submitted and then the outcome of the meeting with the agency will determine next steps. So we'll update when we have something new to share, but the meeting will happen in the first quarter of the year.

當然。因此，會議請求將在年底前提交。根據這項要求，會議將在第一季的某個時間舉行。因此，到了春季晚些時候，最終的企業社會責任報告將提交，然後與該機構的會議結果將決定下一步。所以，一旦有新的消息要分享，我們會及時更新，但會議將在今年第一季舉行。

Brian Skorney, Baird.

Brian Skorney，Baird。

Hey. Good afternoon. Thank you for taking the question. I guess the study has been running for 10 years now and the original design was six-minute walk. And I don't think it was changed to this 4-step Ascend velocity until under -- just under a year ago. And prior to that wasn't flagged as a key secondary endpoint. So I guess with switching the endpoint a mistake, what does the six-minute walk data look like? And what was the rationale last year for changing the analysis?

嘿。午安.感謝您回答這個問題。我猜這項研究已經進行了 10 年，最初的設計是步行 6 分鐘。而且我認為直到大約一年前，它才被改為這種 4 步上升速度。在此之前，它並未被標記為關鍵的輔助端點。所以，如果改變終點是個錯誤，那麼六分鐘步行資料是什麼樣的呢？去年改變分析方法的理由是什麼？

Louise do you want to take this?

路易絲，你想拿這個嗎？

Sure. Yes. So the -- we evaluated the endpoints following our ELEVIDYS EMBARK data. And so we did an analysis of endpoints and engaged external KOLs to help us do that moving to an endpoint that was perhaps more sensitive in this. And based on the data, we -- taking the 4-stair climb versus the six-minute walk test was the right decision in terms of it was determined to be the most sensitive endpoint in our hierarchy.

當然。是的。因此，我們根據 ELEVIDYS EMBARK 數據評估了終點。因此，我們對終點進行了分析，並邀請外部 KOL 幫助我們進行分析，轉向一個可能更敏感的終點。根據數據，我們決定採用 4 級台階爬測試而不是 6 分鐘步行測試，因為它被確定為我們等級體系中最敏感的終點。

And I think the additional analyses we did from both a COVID perspective and a prognostic scoring method also showed that when you applied those thresholds, we see that the -- in terms of COVID, we see almost reached significance. And then when we did with prognostic scoring method, we did see that we reached significance. So it was certainly the right endpoint for the study.

而且我認為，我們從 COVID 的角度和預後評分方法進行的額外分析也表明，當這些閾值應用時，我們看到——就 COVID 而言，我們看到幾乎達到了顯著性。然後，當我們採用預後評分方法時，我們發現結果具有統計意義。所以這無疑是這項研究的正確終點。

Ritu Baral, TD Cowan

Ritu Baral，TD Cowan

Good afternoon, guys. Thanks for taking the question. I wanted to dig in a little further on the dynamics that will drive the down quarter next quarter. Can you elaborate on, I guess, the changes in shipments? I mean, is this sort of a lag on the delay that the disruption or the shipping disruption caused? Or is it something more fundamental? And sort of wrapped in all of this is how is safety monitoring around ALIs changing for the ambulatory patients?

下午好，各位。感謝您回答這個問題。我想更深入地探討一下導致下一季業績下滑的各種因素。能否詳細說明一下出貨量的變動？我的意思是，這是否是運輸中斷或物流中斷造成的延誤的滯後效應？或者，這是更根本的問題？所有這些都與一個問題密切相關：對於門診患者而言，ALI 的安全監測發生了哪些變化？

Are you finding that clinicians are sort of adopting these new monitoring suggestions that were detailed in World Muscle for ambulatory patients? And is that slowing things down? Thanks.

您是否發現臨床醫師正在逐漸採納《世界肌肉》中詳細介紹的這些針對門診病患的新監測建議？這樣會拖慢進度嗎？謝謝。

Yes. I'm going to turn this over to Patrick. I mean let me say in the broadest of stroke, Ritu, it is the downstream pail that occurs when we have this massive disruption. I know people were a bit surprised that we were resistant to this temporary pause. But you can see the impact.

是的。接下來交給派崔克。我的意思是，Ritu，讓我概括地說，這就是當我們遭遇這種大規模混亂時，下游產生的連鎖反應。我知道大家對我們不願接受這種暫時的暫停感到有些驚訝。但你可以看到它的影響。

We had a temporary pause for a very short period of time, but that really creates a significant downstream disruption. We've said many times, the process to go from start form to an infusion can be four to six months. So there's just a resonating impact when you have just a complete pause and then you have to restart everything. But Patrick, you can provide more nuance than I can on this.

我們曾短暫暫停過一段時間，但這確實對下游造成了重大干擾。我們已經多次說過，從開始填寫表格到輸液的過程可能需要四到六個月。所以，當你完全停下來，然後不得不重新開始一切時，就會產生強烈的共鳴。但派崔克，在這方面你能提供比我更細緻的見解。

Absolutely. And I'll add, in addition to what Doug just shared, we have really three dynamics this quarter. One, the medical conferences to where many of our HCPs are out of their offices for many days, weeks at a time. We've got also the major holidays that are going to impact infusions. And then the third is the inevitable illnesses that can pop up this time of the year.

絕對地。除了 Doug 剛剛分享的內容之外，我還要補充一點，本季我們實際上有三種動態。第一，許多醫護人員會參加醫學會議，一去就是好幾天甚至好幾週，無法上班。我們還有一些重大假日也會對輸液產生影響。第三點是每年這個時候不可避免的各種疾病。

So all that comes together and it's what we've seen last year as well could impact this quarter's infusions. And so that's why we're projecting this quarter to be flat to possibly down in the fourth quarter.

因此，所有這些因素加在一起，就像我們去年看到的那樣，可能會影響本季的注資。因此，我們預計本季業績將持平，第四季可能會出現下滑。

David Wang, Deutsche Bank.

大衛王，德意志銀行。

Hi, thanks for taking my question. So I guess maybe following up on some of the ELEVIDYS dynamics that were already asked about. Are you at a place where you can kind of provide a little bit of color on when you think ELEVIDYS demand would be normalized and we might see an inflection in revenues? And then as you think about some of the other competitor gene therapy products out there, one of which I think is seeking accelerated approval sometime next year, does that factor into kind of how you think about how ELEVIDYS demand may play out? Thanks.

您好，感謝您回答我的問題。所以我想，或許可以繼續探討之前有人問過的一些關於 ELEVIDYS 的動態問題。您能否大致說明一下，您認為 ELEVIDYS 的需求何時才能恢復正常，以及我們何時才能看到收入出現拐點？然後，當你考慮到市場上其他一些競爭對手的基因治療產品時，其中一款產品我認為正在尋求明年某個時候獲得加速批准，這是否會影響你對 ELEVIDYS 需求可能如何發展的看法？謝謝。

I'm not going to comment on nor editorialize on other people's claims with their drugs. But as it relates to commercial performance, Patrick, perhaps you want to provide some commentary on that?

我不會對其他人關於藥物的說法發表評論或做出任何評判。但就商業表現而言，派崔克，或許你想就此發表一些看法？

Yes. And the early view is that based on our commercial execution and the trends that we're seeing, it does support that floor that we talked about. As we get further into this quarter, we'll also see additional demands and additional enrollment forms come in, and we'll be able to give an update at a later time, more likely the JPMorgan time frame.

是的。初步看來，根據我們的商業執行情況和我們所看到的趨勢，這確實支持了我們之前談到的最低限度。隨著本季深入發展，我們還將看到更多的需求和更多的報名表，我們將在稍後的時間，更可能是摩根大通的時間框架內，提供最新資訊。

Mitchell Kapoor, H.C. Wainwright.

米切爾·卡普爾，H.C. 溫賴特。

Hi. Thanks for taking our questions. This is [Jade] on for Mitchell. So you stated today that the majority of previous ELEVIDYS cancellations were reordered, but can you provide the actual hard numbers on the infusion postponements versus the number of cancellations you've gotten? And do you have like an actual number of start forms that have been filed for this third quarter?

你好。謝謝您回答我們的問題。這是[Jade]替Mitchell上場。所以您今天表示，之前大部分 ELEVIDYS 取消的訂單都已重新安排，但是您能否提供輸液延期與取消訂單數量的實際確切數字？你們有第三季實際收到的申請表數量嗎？

Yes. We're going to use revenue as our metric. So we're not going to provide that level of detail. Do you have anything to say, Patrick, about the canceled doses, you can certainly touch on that.

是的。我們將以營收作為衡量標準。所以我們不會提供那麼詳細的資訊。派崔克，關於取消的疫苗劑量，你有什麼要說的嗎？當然可以談談這個話題。

Yes. So during the pause, we had 14 cancellations, and we have seen 11 of those patients rescheduled and were redosed within the August time frame, and the remainder are still working through the system.

是的。因此，在暫停期間，我們有 14 個取消的預約，其中 11 名患者已在 8 月重新安排了預約並接受了補種，其餘患者仍在透過系統進行處理。

Barron Amin, Piper Sandler.

巴倫·阿明，派珀·桑德勒。

Yeah. Hi, guys. Thanks for taking my questions. I had a question on ESSENCE. Patients missed doses due to COVID, then you should expect dystrophin production on western blot and percentage of dystrophin-positive fibers to also be impacted between COVID and non-COVID patients. However, there was an analysis that I think the company presented interim data on at the World Muscle Meeting in October 2022 at week 48, that analysis showed no impact for 43 patients that were randomized to either AMONDYS or placebo on exon skipping dystrophin production, dystrophin-positive fibers, dystrophin intensity. Each of these endpoints were evalue static. So I just want to kind of understand how do you correlate that interim AMONDYS data on these biomarkers to the final functional data where you did see a COVID impact? Thanks.

是的。嗨，大家好。謝謝您回答我的問題。我有一個關於ESSENCE的問題。如果患者因 COVID 而錯過劑量，那麼你應該預期，COVID 患者和非 COVID 患者之間，蛋白質印跡法檢測的肌營養不良蛋白產量和肌營養不良蛋白陽性纖維的百分比也會受到影響。然而，我認為該公司在 2022 年 10 月的世界肌肉大會上公佈了第 48 週的中期數據，該分析顯示，對於隨機分配到 AMONDYS 或安慰劑組的 43 名患者，外顯子跳躍肌營養不良蛋白的產生、肌肉營養不良蛋白陽性纖維、肌肉營養不良蛋白強度均無影響。這些端點均被靜態評估。所以我想了解一下，您是如何將 AMONDYS 中期生物標記數據與最終功能數據（您確實在這些數據中看到了 COVID 的影響）關聯起來的？謝謝。

Louise. Do you have a comment on that?

路易絲。您對此有何評論？

Yes. A couple of points on that. So we'll -- once we have all of the final data, we can certainly do a sensitivity analysis to look at this. I think one thing to remember is that the patients didn't have -- there's not a single patient that had biopsies at each time point. So it's difficult to track.

是的。關於這一點，有幾點需要說明。所以，一旦我們拿到所有最終數據，我們當然可以進行敏感度分析來研究這個問題。我認為需要記住的一點是，這些患者並沒有——沒有一個患者在每個時間點都接受了活檢。所以很難追蹤。

So all patients had baseline biopsies and then a subset had them at 48 and another at 96. And so once we have all the data, we can go back and look for sensitivity to see if there was an impact on dystrophin expression. But it is complicated by the fact that not every -- that the patients didn't have sequential biopsies in the study in terms of 48 and 96 weeks, there were separate patients.

因此，所有患者都進行了基線活檢，然後一部分患者在 48 歲時進行了活檢，另一部分患者在 96 歲時進行了活檢。因此，一旦我們掌握了所有數據，我們就可以回頭查看敏感性，看看是否對肌肉營養不良蛋白的表達產生了影響。但問題在於，並非所有患者——研究中的患者並沒有在 48 週和 96 週進行連續活檢，而是有多名患者分別接受活檢。

Gavin Clark Gardner, Evercore.

Gavin Clark Gardner，Evercore。

Hey, guys. I just wanted to follow up on the ELEVIDYS trajectory question. So acknowledging there can be a four- to six-month lag, as you noted, have you seen a pickup in start forms over the last one to two months that gives you confidence there will be a notable revenue pickup in 2026?

嘿，夥計們。我只是想跟進一下關於 ELEVIDYS 軌蹟的問題。鑑於可能存在四到六個月的滯後，正如您所指出的，在過去一到兩個月裡，您是否看到創業表格的數量有所回升，從而讓您相信 2026 年的收入將顯著增長？

Patrick?

派崔克？

We're starting to see sites identify patients and send in their enrollment form. Every patient has a very distinct journey that they have to go through. So it's the antibody screening and the testing and their prescreening before they even start the authorization process. And so the early trends are supporting the positive outlook. And as we get more data, we'll share at a later time.

我們開始看到一些網站識別患者並提交他們的登記表。每位患者都有其獨特的治療歷程。所以，這包括抗體篩檢、檢測以及在開始授權流程之前進行的預篩檢。因此，早期趨勢支持樂觀的預期。隨著我們獲得更多數據，我們將在稍後分享。

Yagel Yelkomovitz, Citi.

Yagel Yelkomovitz，花旗集團。

Hi, this is Jerome Kim. Thanks for taking our question. Maybe just two quick ones from us. Regarding ELEVIDYS, can you speak on whether you're currently seeing prescribers use sirolimus prophylactically for ambulatory patients? And for non-amb patients, can you remind us on the latest thinking around balancing the potential higher risk of infection from using sirolimus and if there was any discussion amongst KOLs or FDA did not utilize sirolimus prophylactically in all non-amb patients given this risk? Thank you.

大家好，我是傑羅姆金。感謝您回答我們的問題。我們可能就簡單提兩句。關於 ELEVIDYS，您能否談談您目前是否看到處方醫生將西羅莫司用於門診患者的預防性治療？對於非門診患者，您能否提醒我們一下關於使用西羅莫司可能增加感染風險的最新看法，以及KOL或FDA是否就此風險進行過討論，從而決定不對所有非門診患者預防性使用西羅莫司？謝謝。

All right. With respect to the latter question on the non-ambulatory, that will be the outcome of our study. We feel pretty confident going into it that the risk benefit is going to justify the prophylactic use of sirolimus, but we'll only know that when the study read out and we look at those issues versus potential issues associated with risk of infection. I will say that to your first question, we only -- we don't have a systematic look at what physicians might be using prophylactic sirolimus there. We definitely have anecdotal evidence that a significant number, particularly more sophisticated physicians have used it.

好的。至於後一個關於非行走能力的問題，這將是我們研究的結果。我們有相當的信心認為，西羅莫司的預防性使用風險收益是合理的，但只有在研究結果出來，我們將這些問題與感染風險相關的潛在問題進行比較之後，我們才能知道這一點。關於你的第一個問題，我想說的是，我們只是——我們沒有系統地調查醫生們可能在那裡使用預防性西羅莫司的情況。我們確實有軼事證據表明，相當多的醫生，特別是經驗豐富的醫生，都使用過這種方法。

And what we're hearing at least anecdotally is that they're not having a lot of problems with the use of sirolimus prophylactically. So what we've at least heard anecdotally is that there some are using it and they are finding it very manageable and I think trying the benefit from it. But this all has to be confirmed. And we have a study that we're going to start when we get to go ahead with the FDA, which hopefully, again, will be very soon. And then we'll be off and then we'll get the data back and we'll get to review it if we are confident that it's significantly changed the risk benefit.

至少從一些非正式的報導來看，他們在預防性使用西羅莫司方面並沒有遇到太多問題。至少我們從一些軼事中聽說，有些人正在使用它，他們發現它非常容易管理，我認為嘗試從中受益是值得的。但這一切都需要證實。我們計劃在獲得 FDA 批准後啟動一項研究，希望很快就能獲得批准。然後我們就會出發，之後我們會收到數據，如果我們確信風險收益發生了顯著變化，我們就會對其進行審查。

We certainly have a lot of conviction that it could, and we're going to talk to the FDA and start testing non-ambulatory patients again.

我們對此深信不疑，我們將與美國食品藥物管理局 (FDA) 進行溝通，並重新開始對無法行走的患者進行測試。

Sammy Corwin, William Blair.

薩米·科溫，威廉·布萊爾。

Good afternoon. Thanks for taking my question. Given the turnover at FDA, I understand that you had written guidance previously from the head of Neuro. But I guess what was the last time you interacted with the division regarding the ESSENCE trial? And then just curious on the percent of patients that missed consecutive doses in the ESSENCE trial that were in the non-COVID group.

午安.謝謝您回答我的問題。鑑於 FDA 的人員更迭，我了解到您之前曾收到過神經部門負責人的書面指導。但我很好奇，你上次就 ESSENCE 審判事宜與該部門進行溝通是什麼時候？我還想知道在 ESSENCE 試驗中，非 COVID 組患者中漏服連續劑量的比例是多少。

As it related to that second issue on the consecutive doses, I think it more than doubled or around doubled in the COVID period versus the COVID-free period. We haven't had any specific discussions other than administrative-related discussions with the agency regarding ESSENCE over the last bit of time, certainly not in the last six months, I don't believe, unless Louise corrects me. But again, I think we're working with the -- I know you've seen without editorial (inaudible) you see all this sort of turmoil at the FDA leadership level recently over the last few days. But I think at the division level, that's where this decision is going to be made. And I'm confident that the professionals in the division are going to take a careful look at this.

至於第二個關於連續接種劑量的問題，我認為在新冠疫情期間，其劑量比非新冠疫情期間增加了一倍以上或接近一倍。在過去一段時間裡，除了與該機構進行一些行政相關的討論之外，我們沒有就 ESSENCE 進行任何具體的討論，至少在過去的六個月裡沒有，除非 Louise 糾正我。但是，我認為我們正在與——我知道你們已經看到，最近幾天，FDA領導層出現了各種各樣的動盪，儘管沒有編輯（聽不清楚）。但我認為，最終的決定將在部門層級做出。我相信該部門的專業人員會認真調查此事。

And I think we are going to be in good shape with respect to marketing authorization. And I'm hopeful that we'll actually be in good shape when we talk to them about transitioning from accelerated approval to traditional approval.

我認為我們在市場進入方面會進展順利。我希望，當我們和他們討論從加速審批過渡到傳統審批時，我們能夠順利進行。

Kristen Kluska, Cantor Fitzgerald.

克里斯汀·克魯斯卡，坎托·費茲傑拉。

Hi, this is Rick Miller on for Kristen. Thanks for taking our question. Just one here. To follow up on the MISSION trial, you said good readout next year for EXONDYS. Do you have any insight on how the FDA might look at any of these dose-ranging data you could generate there? Would you plan to meet with the agency after that trial?

大家好，我是瑞克米勒，替克莉絲汀為你報道。感謝您回答我們的問題。這裡就一個。關於 MISSION 試驗，您說 EXONDYS 明年會有不錯的結果。您認為FDA會如何看待您產生的這些劑量範圍數據？審判結束後，您是否計劃與該機構會面？

And just any insight you can give on what that conversation might look like?

您能否就這場對話可能的形式提供一些見解？

Yes. I think it's going to look at the totality of the evidence from that study and just ask the question, is there a benefit to these patients by increasing the dose perhaps to 100 mg per kg versus the 30 mg per kg, and it's going to be a totality of that evidence about whether that occurs or not is on the one hand, there might be a benefit. We might see some benefit either functionally or in expression. On the other hand, it has to be -- has to rise to a certain bar because we are seeing a benefit from EXONDYS at 30 mg per kg, and that already takes nearly an hour a week. And if you start increasing the dose to 100, certainly 200 is probably not actually viable for these patients.

是的。我認為它會審視該研究的全部證據，並提出這樣一個問題：將這些患者的劑量從每公斤 30 毫克增加到每公斤 100 毫克，是否會帶來益處？它將綜合所有證據來判斷是否存在這種益處，一方面，可能會有益。我們或許能在功能或表達上看到一些益處。另一方面，它必須達到一定的標準，因為我們看到每公斤體重 30 毫克的 EXONDYS 就能帶來益處，而這每週已經需要近一個小時的時間。如果劑量增加到 100，那麼 200 對這些患者來說肯定是不可行的。

The amount of time that you're infusing these kids is enormous and the imposition is extraordinary. So that's the whole thing we have to look at and then together decide if -- I mean, the good news is we're going to be completely aligned in our view of the agency and us. If 100 mg per kg was superior to 30 mg per kg for these kids and the risk benefit and the administrative issues justified it, we'd be fine doing that, but we need to look at that data very carefully. So again, the MISSION is not a confirmatory study. The result of MISSION will either be we're going to be continuing to distribute EXONDYS at 30 mg per kg or we're going to be distributing EXONDYS at some dose higher than 30 mg per kg.

你花在這些孩子身上的時間非常多，施加的壓力也非比尋常。所以這就是我們必須考慮的全部問題，然後共同決定——我的意思是，好消息是我們對機構和我們自身的看法將完全一致。如果對於這些孩子來說，每公斤體重 100 毫克比每公斤體重 30 毫克更好，而風險收益和管理問題都證明這樣做是合理的，那麼我們就可以這樣做，但我們需要非常仔細地研究這些數據。所以再次強調，MISSION 不是一項驗證性研究。MISSION 的結果要么是我們會繼續以每公斤 30 毫克的劑量分發 EXONDYS，要么是我們會以高於每公斤 30 毫克的劑量分發 EXONDYS。

And if it was higher, it will very likely be 100 mg per kg.

如果含量更高，很可能是每公斤100毫克。

Andy Chen, Wolf Research.

安迪陳，狼研究公司。

Thank you for taking the question. This is Brandon on for Andy. Regarding your floor assumptions on ELEVIDYS sales, to what degree are you factoring competitive pressures from emerging therapies?

感謝您回答這個問題。這是布蘭登替安迪發言。關於您對 ELEVIDYS 銷售額的最低預期，您在多大程度上考慮了新興療法帶來的競爭壓力？

We consider emerging therapies. Again, this is just a stress test. It's not our guidance. It's just, you know, this is a number that we would be very comfortable with being able find financial shape we'd be able to make a revolver and you know pay our debts and advance all of our programs so i'm feeling very comfortable about that as a floor.

我們會考慮新興療法。再次聲明，這只是一次壓力測試。這不是我們制定的指導方針。你知道，這個數字讓我們感到非常安心，我們能夠找到合適的財務狀況，建立循環信貸，償還債務，推進所有項目，所以我對這個數字作為底線感到非常放心。

And that concludes our Q&A session. I will now turn the conference back over to Doug for closing remarks.

我們的問答環節到此結束。現在我將把會議交還給道格，請他作閉幕致詞。

Well, thank you all very much for spending some time with us this evening. We all look forward to continuing to update you as we get through the rest of this year, and we'll have some additional milestones. And as we look forward into next year, we'll provide updated guidance next year, of course. And then we're really excited early next year to provide you an update on the actual clinical data from our siRNA programs. That's enormously important to us.

非常感謝各位今晚抽空陪伴我們。在今年餘下的時間裡，我們期待繼續向大家報告最新進展，我們也將取得一些新的里程碑。展望明年，我們當然會提供更新後的指導意見。然後，我們非常興奮地期待在明年初向您提供我們 siRNA 計畫的實際臨床數據的最新進展。這對我們來說至關重要。

So with that, have a lovely evening.

那麼，祝您有個美好的夜晚。

And this concludes today's conference call. Thank you for your participation. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線了。