Sarepta Therapeutics Inc (SRPT) 2024 Q3 法說會逐字稿

Good day and welcome to the Sarepta Therapeutics third-quarter 2024 financial results conference call. (Operator Instructions)

美好的一天，歡迎參加 Sarepta Therapeutics 2024 年第三季財務業績電話會議。（操作員說明）

As a reminder, today's conference is being recorded. At this time, I would like to turn the call over to Mary Jane, Associate Director, Investor Relations, and Corporate Communications. Please go ahead.

提醒一下，今天的會議正在錄製中。現在，我想將電話轉給投資者關係和企業傳播部副總監瑪麗·簡。請繼續。

Thank you, Michelle, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the third quarter 2024. The press release is available on our website at sarepta.com, and our 10-K was filed with the Securities and Exchange Commission this afternoon. Joining us on the call today are Doug Ingram, Ian Estepan, Dallan Murray, and Dr. Louise Rodino-Klapac. After our formal remarks, we'll open the call for Q&A.

謝謝米歇爾，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 2024 年第三季的財務表現。新聞稿可在我們的網站 sarepta.com 上獲取，我們的 10-K 已於今天下午向美國證券交易委員會提交。今天加入我們電話會議的有 Doug Ingram、Ian Estepan、Dallan Murray 和 Louise Rodino-Klapac 博士。正式發言後，我們將開始問答環節。

I'd like to note that during this call, we will be making a number of forward-looking statements. Please take a moment to review our slide 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. Actual results could materially differ from these forward-looking statements, and any such risks can materially and adversely affect the business, results of operations, and trading prices for Sarepta's common stock.

我想指出的是，在這次電話會議中，我們將做出一些前瞻性聲明。請花點時間回顧我們在網路廣播上的幻燈片，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 普通股的業務、營運結果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 quarterly report on Form 10-Q filed with the SEC as well as the company's other 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說明，我們鼓勵您查看該公司向 SEC 提交的最新 10-Q 季度報告以及該公司向 SEC 提交的其他文件。該公司不承擔公開更新其前瞻性陳述的任何義務，包括今天根據後續事件或情況提供的任何財務預測。

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 Doug Ingram，他將概述我們最近的進展。道格？

Thank you, Mary. Good afternoon, and thank you for joining Sarepta Therapeutics' third-quarter 2024 financial results conference call. I am pleased to a strong quarter of commercial performance.

謝謝你，瑪麗。下午好，感謝您參加 Sarepta Therapeutics 的 2024 年第三季財務業績電話會議。我對本季強勁的商業表現感到高興。

Earlier today, we reported total net product revenue of about $430 million, growing at 39% versus the same quarter last year. ELEVIDYS net product revenue was $181 million. Our ex-US partner Roche has made good progress in the quarter. And if we include the royalty revenue from Roche's ex-US ELEVIDYS performance, we achieved $190.5 million in the quarter.

今天早些時候，我們報告產品總淨收入約為 4.3 億美元，與去年同期相比成長 39%。ELEVIDYS 產品淨收入為 1.81 億美元。我們的前美國合作夥伴羅氏在本季取得了良好的進展。如果我們將羅氏公司在美國以外的 ELEVIDYS 業績中的特許權使用費收入納入，我們本季的營收為 1.905 億美元。

Even without considering royalty revenue, our ELEVIDYS performance substantially exceeded our prior guidance as well as analysts consensus. We are tracking well to Q4 and 2025 performance consistent with prior guidance. Our PMO sales comprising EXONDYS 51, VYONDYS 53, and AMONDYS 45, achieved approximately $249 million in the third quarter, again, substantially exceeding analysts consensus.

即使不考慮特許權使用費收入，我們的 ELEVIDYS 業績也大大超出了我們先前的指導以及分析師的共識。我們正在很好地追蹤第四季度和 2025 年的業績，與先前的指導一致。我們的 PMO 銷售額（包括 EXONDYS 51、VYONDYS 53 和 AMONDYS 45）在第三季實現了約 2.49 億美元，再次大大超出了分析師的預期。

As anticipated, we are not yet seeing material cannibalization about PMO franchise from ELEVIDYS performance, and we do not expect to see meaningful net cannibalization through 2025. I am also pleased to report that we were again profitable on a GAAP and non-GAAP basis in the third quarter. Dallan Murray, our Chief Customer Officer, will provide more color on commercial performance in a moment.

正如預期的那樣，我們尚未看到 ELEVIDYS 業績對 PMO 特許經營權的實質蠶食，並且我們預計到 2025 年不會出現有意義的淨蠶食。我還很高興地報告，我們在第三季再次根據公認會計原則和非公認會計原則獲利。我們的首席客戶長 Dallan Murray 稍後將提供有關商業表現的更多資訊。

Turning to R&D. We have rationalized and prioritize our pipeline this quarter, and we've made great progress advancing programs. Before I discuss our progress, let me discuss our PPMO program.

轉向研發。本季我們對我們的管道進行了合理化和優先排序，並且我們在推進專案方面取得了巨大進展。在討論我們的進展之前，讓我先討論一下我們的 PPMO 計劃。

You will have seen in our release that we have made decision to discontinue the SRP-5051 development program. This was done after the dialogue with the FDA and their requirements after our own risk-benefit analysis for the program and in consideration for the evolving landscape for Duchenne, including the approval of ELEVIDYS. Now one that we take slightly the decision to discontinue a program but we are confident that our decision is the right one for the patient community and for our stakeholders.

您將在我們的新聞稿中看到，我們已決定停止 SRP-5051 開發計畫。這是在我們自己對該計劃進行風險效益分析後與 FDA 進行對話並考慮他們的要求後完成的，並考慮到 Duchenne 不斷變化的前景，包括 ELEVIDYS 的批准。現在，我們稍微決定終止一項計劃，但我們相信我們的決定對於病患社群和我們的利害關係人來說是正確的。

Moving to our pipeline progress, we are beginning to move rapidly into late-stage clinical with a planned approval BLA in 2025 for SRP-9003 to treat limb-girdle muscular dystrophy, or LGMD type 2E, the commencement of our trial for SRP-9004 to treat LGMD type 2D in the fourth quarter of this year, and the commencement of our trials for SRP-9005 to treat LGMD type 2C in early 2025. Both of which trials are intended to support accelerated approval.

談到我們的管道進展，我們正開始迅速進入後期臨床，計劃於 2025 年批准 SRP-9003 治療肢帶型肌肉營養不良症或 LGMD 2E 型，這是我們對 SRP-9004 試驗的開始我們將於今年第四季開始治療2D 型LGMD，並於2025 年初開始SRP-9005 治療2C 型LGMD 的試驗。這兩項試驗都旨在支持加速批准。

We have also made progress with our clinical development for ELEVIDYS, including clinical activity to support ex-US approvals and meet our post-marketing commitments. Data presentations that speak to the value of ELEVIDYS to those living with Duchenne, and clinical development work intended to expand the population for ELEVIDYS.

我們在 ELEVIDYS 的臨床開發方面也取得了進展，包括支持美國以外的批准和履行我們的上市後承諾的臨床活動。數據演示說明了 ELEVIDYS 對 Duchenne 患者的價值，以及旨在擴大 ELEVIDYS 族群的臨床開發工作。

Additionally, our program to move ELEVIDYS to suspension manufacturing is proceeding very well. We have had very encouraging interactions with the FDA, and we continue our engineering runs in anticipation of commencing a bridging study in 2025.

此外，我們將 ELEVIDYS 轉向懸吊製造的計劃進展順利。我們與 FDA 進行了非常令人鼓舞的互動，我們將繼續我們的工程運行，預計在 2025 年開始橋接研究。

We have also made good progress with the rest of our neuromuscular CNS and cardiomyopathy pipeline intend to share more concerning our pipeline and its progress in 2025. Our Head of R&D and Chief Scientific Officer, Dr. Louise Rodino-Klapac, will discuss this decision and our R&D progress in a moment.

我們的神經肌肉中樞神經系統和心肌病變產品線的其餘部分也取得了良好進展，打算在 2025 年分享更多有關我們的產品線及其進展的資訊。我們的研發主管兼首席科學長 Louise Rodino-Klapac 博士稍後將討論這項決定和我們的研發進展。

And with that, I will turn the call to Dallan Murray for more detail on commercial performance and our plans. Dallan?

接下來，我將致電達蘭·莫瑞（Dallan Murray），以了解有關商業表現和我們計劃的更多詳細資訊。達蘭？

Thank you, Doug, and good afternoon. We're pleased to report an impressive third quarter, led by the continued strength of the ELEVIDYS launch. The success and performance we've achieved since approval has been and continues to be driven by robust patient demand for both the ambulant and non-ambulant populations, ample seat capacity, positive trends in access and reimbursement, and consistent conversion rates. But we continue to see patients gaining access within the three to five months conversion timeline.

謝謝你，道格，下午好。我們很高興地報告第三季業績令人印象深刻，其中 ELEVIDYS 的推出持續強勁。自批准以來，我們所取得的成功和業績一直並將繼續受到患者對流動和非流動人群的強勁需求、充足的座位容量、准入和報銷的積極趨勢以及一致的轉換率的推動。但我們繼續看到患者在三到五個月的轉換時間內獲得訪問權限。

Additionally, as the team works to execute on the broad label, it's important to note that we've thoughtfully built a model which allows us to flex data to accommodate demand from different segments such as the older non-ambulatory population.

此外，當團隊致力於在廣泛的標籤上執行時，值得注意的是，我們精心構建了一個模型，該模型使我們能夠靈活調整數據以滿足不同群體（例如老年人非流動人群）的需求。

Turning to the third-quarter revenue numbers. Net product revenue for ELEVIDYS raised $181 million and grew by nearly 50% compared to the prior quarter, exceeding our guidance of quarter-to-quarter growth of 30%. Of note and looking forward, I remain impressed with our team's ability to forecast because we have shown with our performance this quarter, we have good visibility on the launch dynamics, and as predicted, we are now at the inflection point on the launch curve.

轉向第三季的營收數據。ELEVIDYS 的淨產品收入增加了 1.81 億美元，與上一季相比成長了近 50%，超過了我們 30% 的季度成長預期。值得注意的是，展望未來，我對我們團隊的預測能力仍然印象深刻，因為我們本季度的業績表明，我們對發布動態有良好的可見性，並且正如預測的那樣，我們現在正處於發布曲線的轉折點.

Further enhanced by the wealth of data presented at World Muscle that Louise will discuss, we have strong momentum going into the fourth quarter and reiterate our previously stated Q4 guidance, which is in line with the current Q4 consensus. Based on all of these factors and our confidence in meeting the Q4 expectations, we remain in a strong position to achieve guidance for 2025.

路易絲將討論的世界肌肉大會上提供的大量數據進一步增強了我們進入第四季度的強勁勢頭，並重申了我們之前提出的第四季度指引，這與當前第四季度的共識一致。基於所有這些因素以及我們對滿足第四季度預期的信心，我們仍然有能力實現 2025 年的指導。

The progress made by this team is unprecedented in our industry. We've anticipated all of the factors necessary to execute on a broad label, and our performance provides clear evidence of our continued ability to meet expectations and execute as promised.

這個團隊所取得的進步在我們這個行業中是前所未見的。我們已經預見了在廣泛的標籤上執行所需的所有因素，並且我們的表現清楚地證明了我們持續有能力滿足期望並按承諾執行。

So to summarize, we continue to see high demand, strong conversion rates, and we are impressed with how sites of care are successfully treating patients at an unprecedented rate. Together, we are changing the face of Duchenne muscular dystrophy in the United States.

總而言之，我們繼續看到高需求和強勁的轉換率，並且我們對護理場所如何以前所未有的速度成功治療患者印象深刻。我們正在共同改變美國杜氏肌肉營養不良症的面貌。

Turning to our PMO franchise, which also achieved impressive results in the third quarter. Importantly, we expect to see continued strength in the coming quarters and years. We delivered roughly $249 million in net product revenue. It was approximately 4% growth in Q3 compared to the third quarter of 2023. The PMO's representing a healthy and solid segment of our Duchenne franchise.

轉向我們的 PMO 特許經營權，該特許經營權在第三季度也取得了令人印象深刻的業績。重要的是，我們預計未來幾個季度和幾年將繼續保持強勁勢頭。我們的產品淨收入約為 2.49 億美元。與 2023 年第三季相比，第三季成長約 4%。PMO 代表了我們 Duchenne 特許經營權的健康和堅實的部分。

EXONDYS 51 led the way for the PMOs at $140.7 million in net revenue. VYONDYS 53 delivered $32.2 million in net product revenue in the third quarter. And we delivered $75.9 million in net product revenue for AMONDYS 45 in Q3, representing growth of nearly 15% compared to Q3 of 2023.

EXONDYS 51 以 1.407 億美元的淨收入領先 PMO。VYONDYS 53 第三季的產品淨收入為 3,220 萬美元。第三季度，我們為 AMONDYS 45 帶來了 7,590 萬美元的產品淨收入，與 2023 年第三季相比成長了近 15%。

In closing, I'd like to thank the Sarepta team and all of our partners, whether at the sites of care or elsewhere. And most importantly, I'd like to thank the patient community who have been with us on this pioneering journey every step of the way. We're grateful to be exactly where we had always wanted to be, and that is with approved therapies serving the vast majority of physician patient community.

最後，我要感謝 Sarepta 團隊和我們所有的合作夥伴，無論是在護理地點還是其他地方。最重要的是，我要感謝患者社區，他們在這開創性旅程的每一步都與我們同在。我們很高興能夠實現我們一直想要達到的目標，那就是為絕大多數醫生患者群體提供經批准的治療方法。

And with that, I'll hand the call over to Dr. Louise Rodino-Klapac for the R&D update. Lousie?

接下來，我會將電話轉交給 Louise Rodino-Klapac 博士，了解研發最新情況。路易斯？

Thanks, Dallan. I'll begin my remarks with ELEVIDYS and then provided in our pipeline. We continue to advance the ELEVIDYS clinical program and share new data as they become available. We recently published the primary one-year EMBARK results in Nature Medicine, a high-impact journal. In addition, we had multiple presentations at the World Muscle Society Congress in early October. This included additional EMBARK data, muscle MRI, and cardiac MRI.

謝謝，達蘭。我將從 ELEVIDYS 開始我的發言，然後在我們的管道中提供。我們將繼續推進 ELEVIDYS 臨床計劃並分享新數據。我們最近在高影響力期刊《自然醫學》上發表了第一年的 EMBARK 結果。此外，我們也在十月初的世界肌肉協會大會上進行了多次演講。這包括額外的 EMBARK 數據、肌肉 MRI 和心臟 MRI。

Muscle MRI changes were consistent with functional outcomes from EMBARK Part 1 showing stabilization or slowing of disease progression with SRP-9001, where progression occurred in placebo-treated patients, evidenced by accumulation of fat and fibrosis. Cardiac MRI demonstrated that at one year post-gene therapy, there was no evidence of comments there. Future longitudinal cardiac MRI studies to assess long-term protection cardiac muscle.

肌肉 MRI 變化與 EMBARK 第 1 部分的功能結果一致，顯示 SRP-9001 穩定或減緩了疾病進展，其中進展發生在安慰劑治療的患者中，透過脂肪積累和纖維化來證明。心臟 MRI 表明，基因治療後一年，沒有任何評論證據。未來的縱向心臟 MRI 研究將評估心肌的長期保護作用。

As we've previously described, ELEVIDYS campaigns and MHCK7 promoter that expresses well in the heart to protect cardiac muscle. We have shown in the MDX rat model of Duchenne improvements in cardiac function as well as overall survival.

正如我們之前所描述的，ELEVIDYS 運動和 MHCK7 啟動子在心臟中表達良好，可以保護心肌。我們在杜氏 MDX 大鼠模型中證明了心臟功能和整體存活率的改善。

In addition to the EMBARK data, we've also presented safety and expression data from Study 103 or ENDEAVOR, demonstrating consistent safety and expression data across ambulatory and non-ambulatory patients. As at the end of October 2024, we have dosed over 80 late ambulatory and non-ambulatory patients within our clinical program and continue to see a consistent safety profile.

除了 EMBARK 數據外，我們還提供了研究 103 或 ENDEAVOR 的安全性和表達數據，證明了門診和非門診患者的安全性和表達數據一致。截至 2024 年 10 月底，我們已在臨床計劃中對 80 多名晚期臥床和非臥床患者進行了給藥，並繼續看到一致的安全性。

Finally, we shared five-year longitudinal data from Study 101, demonstrating that SRP-9001 stabilizes or slow DMD progression with an increase in divergence from natural history over time. As shown by external control analysis and supported by the independent cTAP analysis. No new safety signals were identified.

最後，我們分享了研究 101 的五年縱向數據，證明 SRP-9001 可以穩定或減緩 DMD 的進展，隨著時間的推移，與自然史的差異會增加。如外部對照分析所示並得到獨立 cTAP 分析的支持。沒有發現新的安全訊號。

As mentioned on our last call, the ELEVIDYS accelerated approval for non-ambulatory patients include the post-marketing confirm clinical benefit, which will be addressed to be our non-ambulatory and late-ambulatory study 303, also known as ENVISION. As a reminder, ENVISION is a global, randomized, double-blind placebo-controlled two-part study.

正如我們上次電話會議中提到的，ELEVIDYS 對非臥床患者的加速批准包括上市後確認的臨床益處，這將在我們的非臥床和晚期臥床研究 303（也稱為 ENVISION）中得到解決。提醒一下，ENVISION 是一項全球、隨機、雙盲、安慰劑對照的兩部分研究。

ENVISION is progressing well with US enrollment complete and the remaining recruitment occurring ex-US. Enrollment is expected to be completed in 2025 with our last patient last visit expected in 2027 following an 18-month placebo-controlled period. We also continue to advance clinical studies that monitor long-term follow-up for the ELEVIDYS. Our long-term follow-up studies include ENDURE and XPEDITION.

ENVISION 進展順利，美國招募已完成，剩餘招募在美國境外進行。入組預計將於 2025 年完成，最後一位患者的最後一次就診預計在 18 個月的安慰劑對照期後於 2027 年進行。我們也持續推進監測 ELEVIDYS 長期追蹤的臨床研究。我們的長期追蹤研究包括 ENDURE 和 XPEDITION。

As a reminder, ENDURE is a Phase 4 observational study that will follow individuals treated with ELEVIDYS for up to 10 years. In addition, XPEDITION is a Phase 3 study enrolling approximately 400 patients that were previously enrolled in ELEVIDYS clinical trials and followed for consistent safety and efficacy measures for up to five years.

提醒一下，ENDURE 是一項 4 期觀察性研究，將對接受 ELEVIDYS 治療的個體進行長達 10 年的追蹤。此外，XPEDITION 是一項 3 期研究，招募了約 400 名患者，這些患者之前曾參加 ELEVIDYS 臨床試驗，並對其進行長達五年的一致安全性和有效性測量。

Regarding patient currently ineligible to receive ELEVIDYS under the expanded label, we continue to advance multiple studies. For the approximately 15% of patients who are screened out for pre-existing anti-AAVrh74 antibodies, we have commenced two studies, one with cleave antibodies and a second with plasmapheresis to remove antibodies. We expect to have expression and safety data from fentanyl patient from early 2025.

對於目前沒有資格在擴大標籤下接受 ELEVIDYS 的患者，我們繼續推進多項研究。對於大約 15% 被篩檢出預先存在的抗 AAVrh74 抗體的患者，我們已經開始了兩項研究，一項是裂解抗體，另一項是血漿去除術以去除抗體。我們預計從 2025 年初開始獲得芬太尼患者的表達和安全性數據。

In addition, for patients under the age of 4, we've treated patients with the youngest 2 in our Study 103, and together with our partner Roche, we are executing Study 302 or INVOLVE, again, experienced dosing patients under 4 and again with 3 months. We continue to communicate a range of trial experience in patients treated with ELEVIDYS from those that are under 4 to those with more advanced disease.

此外，對於4 歲以下的患者，我們在研究103 中治療了最小2 歲的患者，並且與我們的合作夥伴羅氏一起，我們正在執行研究302 或INVOLVE，再次，經驗豐富的4 歲以下患者給藥，並再次使用3個月。我們持續交流 ELEVIDYS 治療患者的一系列試驗經驗，從 4 歲以下患者到晚期疾病患者。

Moving now to our programs for the limb-girdle muscular dystrophies, or LGMD. Starting with SRP-9003, as we mentioned in the first-quarter call, we initiated dosing early this year in Study SRP-9003-301, also known as EMERGENE, our Phase 3 multi-national open-label clinical trials, SRP-9003 for the treatment muscular dystrophy type 2E for beta-sarco-glycanopathy.

現在轉向我們的肢帶型肌肉營養不良症 (LGMD) 計畫。正如我們在第一季電話會議中提到的，從SRP-9003 開始，我們在今年年初的研究SRP-9003-301（也稱為EMERGENE）中開始給藥，這是我們的3 期多國開放標籤臨床試驗SRP-9003用於治療 2E 型肌肉營養不良症的 β-肌聚醣症。

The agreed primary endpoint of EMERGENE is expression of beta-sarcoglycan. The absence of which is the sole cause of the disease. This study is on track to be fully enrolled by the end of 2024. Assuming a positive pre-BLA meeting, we will anticipate a BLA filing in 2025. We're encouraged by the agency's willingness to support a viable pathway for SRP-9003 in ultra-rare genetic condition that is progressively debilitating, results and loss of ambulation, and leads to early mortality.

EMERGENE 一致同意的主要終點是 β-肌聚醣的表達。缺乏它是該疾病的唯一原因。這項研究預計將於 2024 年底全部入組。假設 BLA 前會議取得正面成果，我們預計在 2025 年提交 BLA。我們感到鼓舞的是，該機構願意支持 SRP-9003 在極其罕見的遺傳性疾病中建立可行的途徑，這種遺傳性疾病逐漸使人衰弱，導致行走能力下降，並導致早期死亡。

The ability to progress a small NF15 biomarker study, together with our ability to demonstrate delivery of a functional beta-sarcoglycan protein is extremely important, not just for this program but also for the other sarcoglycan opportunities in our pipeline, including LGMD2D and LGMD2C, both of which are progressing to the clinic.

進行小型NF15 生物標記研究的能力，以及我們證明功能性β-肌聚醣蛋白的交付的能力極為重要，不僅對於該計劃，而且對於我們管道中的其他肌聚醣機會，包括LGMD2D 和LGMD2C，都非常重要。

Having successfully advanced SRP-9003, we submitted our SRP-9004 IND update, reflecting our suspension process this year, with Phase 1 initiation expected by year's end. As a reminder, SRP-9004 is designed for the treatment of limb-girdle muscular dystrophy type 2D, or alpha-sarco-glycanopathy.

成功推進 SRP-9003 後，我們提交了 SRP-9004 IND 更新，反映了我們今年的暫停流程，預計第一階段將於年底啟動。提醒一下，SRP-9004 設計用於治療 2D 型肢帶型肌肉營養不良症或 α-肌肉聚醣症。

Finally, we are also rapidly progressing our program for SRP-9005 for the treatment of limb-girdle muscular dystrophy type 2C, or gamma-sarco-glycanopathy. We plan to engage with FDA in Q4 of this year with plan to initiate a clinical study in Q1 2025.

最後，我們也正在快速推進 SRP-9005 項目，用於治療 2C 型肢帶型肌肉營養不良症或伽瑪肌聚醣症。我們計劃於今年第四季與 FDA 合作，並計劃於 2025 年第一季啟動臨床研究。

To summarize, we're very pleased with the progress of our LGMD portfolio and expect to have three of our LGMDs in the clinic in less than six months. We are maximizing the synergies across this platform from both an R&D and manufacturing perspective, and our sites are firmly set on accelerating the remainder of the LGMD assets to the clinic.

總而言之，我們對 LGMD 產品組合的進展感到非常滿意，並期望在不到六個月的時間內將我們的三個 LGMD 投入臨床。我們正在從研發和製造的角度最大限度地發揮該平台的協同效應，並且我們的基地堅定不移地加速將 LGMD 的剩餘資產推向臨床。

Continuing with our R&D platform and beginning with our PMOs, the ESSENCE trial, our post-marketing requirements for golodirsen and casimersen, as well as MISSION, our post-marketing commitment for EXONDYS, are both fully enrolled and remain on track. We look forward to sharing data as soon as the study is complete.

繼續我們的研發平台，從我們的 PMO 開始，ESSENCE 試驗、我們對 golodirsen 和 casimersen 的上市後要求，以及 MISSION（我們對 EXONDYS 的上市後承諾）均已完全註冊並保持在正軌上。我們期待研究完成後立即分享數據。

Turning now to PPMO. As announced today and in line with our unwavering commitment to patients first, we have decided to discontinue development of SRP-5051, also known as vesleteplirsen, our investigational peptide conjugated PMO or PPMO, to treat Duchenne. This means dosing in our MOMENTUM study, SRP-5051-201 has stopped.

現在轉向 PPMO。正如今天所宣布的，根據我們對患者第一的堅定承諾，我們決定停止開發 SRP-5051（也稱為 vesleteplirsen），我們的研究性肽綴合 PMO 或 PPMO，用於治療 Duchenne。這意味著我們的 MOMENTUM 研究中的 SRP-5051-201 劑量已停止。

The safety of study participants is our highest priority. And while we are encouraged by the dystrophin expression results with SRP-5051, the long-term safety in a chronic treatment setting does not support further development. Our initial hypothesis was that the hypomagnesemia was manageable and monitorable. Although events thus far remained medically manageable, in a small number of patients, we saw persistent hypomagnesemia despite treatment discontinuation, and our risk-benefit analysis led us to end of the study.

研究參與者的安全是我們的首要任務。儘管我們對 SRP-5051 的肌肉營養不良蛋白表達結果感到鼓舞，但慢性治療環境中的長期安全性並不支持進一步開發。我們最初的假設是低鎂血症是可以控制和監測的。儘管到目前為止，事件在醫學上仍然是可以控制的，但在少數患者中，儘管停止治療，我們還是看到了持續的低鎂血症，我們的風險效益分析導致我們結束了研究。

The MOMENTUM study provided important information around the use of RNA-targeted therapies to increase dystrophin production in Duchenne, and we are extremely grateful to the patients, families, and clinicians who participated in our study.

MOMENTUM 研究提供了有關使用 RNA 標靶療法來增加 Duchenne 肌肉營養​​不良蛋白產生的重要信息，我們非常感謝參與我們研究的患者、家屬和臨床醫生。

Now, let's spend a moment discussing our current and future pipeline. During the past six years since I joined Sarepta, we've been diligently building expertise and capabilities to advance our current portfolio and identify new assets. We've significantly advanced the field of genetic medicine through clinical trials and advanced research for patients with preexisting antibodies and the potential for redosing.

現在，讓我們花點時間討論一下我們當前和未來的管道。自從我加入 Sarepta 以來的過去六年中，我們一直在努力建立專業知識和能力，以推進我們當前的投資組合併發現新資產。透過針對已有抗體和可能重新用藥的患者進行臨床試驗和進階研究，我們顯著地推進了基因醫學領域的發展。

We've also advanced regulatory precedent for gene therapy for rare disease as evidenced by a rapidly developing LGMD platform. On the research side, we have optimized, developed, and characterized new AAV capsid that will change the landscape for neuromuscular gene therapy and unlock potential in cardiac and central nervous system disease areas.

我們也推進了罕見疾病基因治療的監管先例，快速發展的 LGMD 平台證明了這一點。在研究方面，我們優化、開發並表徵了新的 AAV 衣殼，這將改變神經肌肉基因療法的格局，並釋放心臟和中樞神經系統疾病領域的潛力。

As an example, we've optimized the construct for Charcot-Marie-Tooth type 1A, or CMT1A, using AAVrh74, and are now rapidly advancing to the clinic following exciting preclinical data.

例如，我們使用 AAVrh74 優化了 Charcot-Marie-Tooth 1A 型或 CMT1A 的構建體，並且在獲得令人興奮的臨床前數據後，現在正在快速推進到臨床。

As a reminder, we're using a surrogate approach for delivery of the neurotrophin 3 or NT-3 gene to improve myelination and nerve regeneration in CNT1A. This pipeline in the product approach has applicability to other CNTs as well as other demyelinating indications. We look forward to highlighting our impressive pipeline in an R&D Day in 2025.

提醒一下，我們正在使用替代方法來傳遞神經營養素 3 或 NT-3 基因，以改善 CNT1A 中的髓鞘形成和神經再生。此產品方法中的管道適用於其他碳奈米管以及其他脫髓鞘適應症。我們期待在 2025 年的研發日上重點展示我們令人印象深刻的產品線。

I'll close by thanking all the patients who participate in our trials and my incredibly talented R&D colleagues who make all of this possible. The future is bright because of their work.

最後，我要感謝所有參與我們試驗的患者以及我才華橫溢的研發同事，他們使這一切成為可能。因為他們的努力，未來是光明的。

I'll now turn the call over to Ian Estepan for an update on our financial results. Ian?

現在我將把電話轉給伊恩·埃斯特潘 (Ian Estepan)，以了解我們財務表現的最新情況。伊恩？

Thanks, Louise, and good afternoon, everyone. The financial results press release provided details for the third-quarter 2024 on a GAAP basis as well as a non-GAAP basis. Please refer to our press release available on our website for full reconciliation of GAAP, non-GAAP financial results.

謝謝，路易絲，大家午安。財務業績新聞稿提供了 2024 年第三季按 GAAP 和非 GAAP 計算的詳細資訊。請參閱我們網站上的新聞稿，以了解 GAAP 和非 GAAP 財務表現的完整對帳資訊。

As a reminder, beginning in the fourth quarter of 2023, amortization of in-license rights and income tax expense are no longer excluded from non-GAAP results. The company has added the income tax effective adjustments, which represents the estimated income tax impact of each of our pre-tax non-GAAP adjustments based on the applicable effective income tax rate. Non-GAAP financial results for the third quarter of 2023 have been updated to reflect this change for comparability purposes.

提醒一下，從 2023 年第四季開始，許可權攤銷和所得稅費用不再排除在非 GAAP 業績之外。本公司增加了所得稅有效調整，代表我們每項稅前非公認會計準則調整根據適用的有效所得稅率估計的所得稅影響。出於可比性目的，2023 年第三季的非 GAAP 財務業績已更新，以反映此變更。

So for the three months ended September 30, 2024, the company recorded total revenues of $467.2 million, which consists of net product revenues and collaboration in other revenues, compared to revenues of $331.9 million for the same period of 2023, an increase of $135.4 million.

因此，截至2024 年9 月30 日的三個月，該公司的總收入為4.672 億美元，其中包括產品淨收入和其他合作收入，與2023 年同期的收入3.319 億美元相比，增加了1.354 億美元。

Net product revenue for the third quarter of 2024 from ELEVIDYS was $181 million compared to $69 million same period of 2023. The increase in net product revenue primarily reflects the net product revenue associated with sales of ELEVIDYS.

ELEVIDYS 2024 年第三季的產品淨收入為 1.81 億美元，而 2023 年同期為 6,900 萬美元。產品淨收入的成長主要反映了與 ELEVIDYS 銷售相關的淨產品收入。

For the three months ended September 30, 2024, the company recognized $37.4 million of collaboration and other revenues, which primarily relates to the commercial ELEVIDYS supply delivered to Roche and royalty revenue from Roche compared to collaboration revenues of $22.5 million for the same period 2023, an increase of $14.9 million.

截至2024年9月30日的三個月，該公司確認了3,740萬美元的合作和其他收入，這主要與向羅氏提供的商業ELEVIDYS供應和羅氏的特許權使用費收入有關，而2023年同期的合作收入為2250萬美元，增加了 1,490 萬美元。

The reimbursable co-development costs under the Roche agreement totaled $61.5 million for the third quarter of 2024 compared to $34.9 million for the same period of 2023. As a reminder, these Roche reimbursable co-development costs aren't offset to our operating expenses.

2024 年第三季羅氏協議下的可報銷共同開發費用總計 6,150 萬美元，而 2023 年同期為 3,490 萬美元。提醒一下，這些羅氏可報銷的共同開發成本並沒有抵銷我們的營運費用。

On a GAAP basis, we reported a net income of $33.6 million, or $0.35 per basic share and $0.34 per diluted share, and a net loss of $40.9 million, or $0.46 per basic and diluted share for the third quarter of 2024 and 2023, respectively. We reported a non-GAAP net income of $67 million, or $0.62 per diluted share in the third quarter of 2024 compared to a non-GAAP net income of $31.5 million, or $0.31 cents per diluted share in the third quarter of 2023.

根據公認會計原則，我們報告2024 年第三季和2023 年第三季的淨利潤為3,360 萬美元，即每股基本股0.35 美元，每股稀釋股0.34 美元，淨虧損為4,090 萬美元，即每股基本股和稀釋股0.46 美元。我們公佈的2024 年第三季非GAAP 淨利潤為6,700 萬美元，即稀釋後每股收益0.62 美元，而2023 年第三季非GAAP 淨利潤為3,150 萬美元，即稀釋後每股收益0.31 美分。

In third quarter of 2024, we recorded approximately $91.7 million in cost of sales compared to $37 million in the same period 2023. The increase in cost of sales primarily reflects the cost of sales related to ELEVIDYS during the three months ended September 30, 2024, following the label expansion in June.

2024 年第三季度，我們的銷售成本約為 9,170 萬美元，而 2023 年同期為 3,700 萬美元。銷售成本的增加主要反映了 ELEVIDYS 在 6 月擴大標籤後截至 2024 年 9 月 30 日止三個月期間的相關銷售成本。

On a GAAP basis, we recorded $224.5 million and $194.3 million in R&D expenses for the third quarter of 2024 and 2023, respectively, a year-over-year increase of $30.2 million. The increase primarily reflects a $55.4 million cost associated with the termination of an inherent commercial manufacturing and supply agreement, net of the reimbursement termination cost by Roche, partially offset by a decrease in clinical and manufacturing activity for our PPMO and accomplishment program.

以公認會計原則計算，2024 年第三季和 2023 年第三季的研發費用分別為 2.245 億美元和 1.943 億美元，年比增加 3,020 萬美元。這一增長主要反映了與終止固有商業製造和供應協議相關的 5540 萬美元成本，扣除羅氏的報銷終止成本，部分被我們的 PPMO 和成就計劃的臨床和製造活動的減少所抵消。

On a non-GAAP basis, R&D expenses were $199.8 million for the third quarter of 2024 compared to $163.9 million for the same period of 2023, an increase of $35.9 million.

以非公認會計原則計算，2024年第三季的研發費用為1.998億美元，而2023年同期的研發費用為1.639億美元，增加了3,590萬美元。

Now turning to SG&A on a GAAP basis, we recorded approximately $128.2 million and $120.9 million of expenses for the third quarters of 2024 and 2023, respectively, an increase of $7.3 million. The increase was primarily driven by an increase in professional services used to support the continued efforts to commercialize ELEVIDYS and an increase in compensation and other personnel expenses primarily related to the changes in headcount.

現在轉向以 GAAP 計算的 SG&A，我們在 2024 年和 2023 年第三季的支出分別約為 1.282 億美元和 1.209 億美元，增加了 730 萬美元。這一增長主要是由於用於支持 ELEVIDYS 商業化持續努力的專業服務的增加，以及主要與員工人數變化相關的薪酬和其他人員費用的增加。

On a non-GAAP basis, the SG&A expenses were $100.2 million for the third quarter of 2024 compared to $92.8 million for the same period of 2023, an increase of $7.4 million. On a GAAP basis, we recorded $11.8 million in other income net for the third quarter of 2024, compared to $12.3 million of other loss net for the same period of 2023. The change is primarily due to an impairment or a strategic investment during the three months ended September 30, 2023, with no similar activity in 2024.

以非公認會計原則計算，2024 年第三季的銷售、管理及行政費用為 1.002 億美元，而 2023 年同期為 9,280 萬美元，增加了 740 萬美元。根據公認會計原則，我們 2024 年第三季的其他淨收入為 1,180 萬美元，而 2023 年同期的其他淨虧損為 1,230 萬美元。這項變更主要是由於截至2023年9月30日的三個月內發生減損或策略性投資，2024年沒有類似活動。

We had approximately $1.4 billion in cash equivalent to investments and long-term restricted cash as of September 30, 2024.

截至 2024 年 9 月 30 日，我們擁有約 14 億美元的現金等值投資及長期限制性現金。

So to conclude, unsurprisingly, our strong commercial execution and our continued focus on expense management has put us in a strong financial position. We now expect to be sustainably profitable from both the GAAP and non-GAAP perspective, and we'll turn cash flow positive early in 2025.

因此，總而言之，毫不奇怪的是，我們強大的商業執行力和對費用管理的持續關注使我們處於強大的財務狀況。我們現在預計從 GAAP 和非 GAAP 角度來看都將實現可持續盈利，並且我們將在 2025 年初實現現金流轉正。

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

然後，我將把電話轉回給道格開始問答。道格？

Thank you very much, Ian. And Michelle, let's open the call for questions.

非常感謝你，伊恩。米歇爾，讓我們開始提問。

(Operator Instructions) Tazeen Ahmad, BofA Securities.

（操作員指示）Tazeen Ahmad，美國銀行證券。

I wanted to clarify what you said a little bit earlier when you're prepped for marks about maintaining guidance for the rest of the year. So when you gave us original guidance, you had said that based on the number you expected in 3Q that you would guide to 100% upside for 4Q results now that you've beaten expectations.

我想澄清一下你之前所說的話，當時你正準備獲得今年剩餘時間維持指導的分數。因此，當您向我們提供最初的指導時，您曾說過，根據您對第三季度的預期數字，您將指導第四季度業績實現 100% 的上漲，因為您已經超出了預期。

Can you tell us what that base number is? Is it 100% upside from what you just reported? Thanks.

可以告訴我們這個基數是多少嗎？與您剛剛報告的相比是否有 100% 的上漲空間？謝謝。

Yeah, we feel very comfortable with the guidance we gave before, which was we'd be 100% above the guidance that we had for Q3.

是的，我們對之前給出的指導感到非常滿意，這比第三季度的指導高出 100%。

I will also linger and note that we are continuing to be very, very comfortable with the guidance we gave for 2025, the long-term guidance, $3 billion, about two-thirds of which will be ELEVIDYS and one-third of which would be our PMOs. And we're also very confident in our long-term projections, which would have peakier sales across the four approved therapies at $5 billion or more, and that we would be treating with ELEVIDYS the prevalent population over the course of the 2020s into 20 -- around 2030 or so, and we'll be growing for some number over the years.

我還要指出的是，我們仍然對我們為 2025 年提供的指導感到非常非常滿意，即長期指導，30 億美元，其中約三分之二將是 ELEVIDYS，其中三分之一將是我們的項目管理辦公室。我們對我們的長期預測也非常有信心，這四種已批准療法的銷售額將達到 50 億美元或更多，並且我們將在 2020 年代用 ELEVIDYS 治療流行人群至 20 歲 - - 大約在2030 年左右，這些年來我們的數量將會成長。

Gena Wang, Barclays.

王吉娜，巴克萊銀行。

Thank you. Since I can only ask one question, I will ask about this PPMO discontinuation of 5051. So maybe can you give a little bit more color regarding the hypomagnesium? Is that the main concern, FDA-raised? Can you give a little bit more color at what point that you see more severe cases?

謝謝。由於我只能問一個問題，所以我就問這個PPMO停產5051的事情。那麼也許你可以對低鎂提供更多的顏色嗎？這是 FDA 提出的主要問題嗎？您能在什麼時候看到更嚴重的病例提供更多資訊嗎？

And also when we -- the old data back, the 30-milligram at the 12 weeks was 6.55% protein expression. And at that time, you project it could be over 10% at 96 weeks. Would the protein level is due in line with what you projected and is mainly is the safety and are you planning to complete discontinue the PPMO franchise?

而且當我們返回舊數據時，12 週時的 30 毫克蛋白質表現量為 6.55%。那時，您預計 96 週時可能會超過 10%。蛋白質水平是否符合您的預期，主要是安全性，您是否計劃完全終止 PPMO 特許經營權？

Yeah, so I will -- first of all, thank you for your question, Gena. I'll turn the question over to Louise to make some comments about our decisions regarding the PPMO program.

是的，所以我會——首先，謝謝你的提問，Gena。我將把問題轉交給 Louise，讓她對我們有關 PPMO 計劃的決定發表一些評論。

Sterling, I'll try to make sure I remember all of the parts. So on the franchise, we are discontinuing the entire PPMO franchise. They all use the same cell-penetrating peptide, and so this also includes the discontinuation of the other PPMO programs.

斯特林，我會盡力確保記住所有部分。因此，在特許經營權方面，我們將終止整個 PPMO 特許經營權。它們都使用相同的細胞穿透勝肽，因此這也包括其他 PPMO 計畫的終止。

The decision to stop the program was based on multi-factorial. So it included our discussions with the FDA, which we've had on the development of that. At this point, the FDA said that the accelerated approval pathway was not open based on the current profile to date. It was primarily based on our own benefit risk assessment, and that was including safety, which included the hypomagnesemia that we saw, which consisted of prolonged hypomagnesemia in some cases.

停止該計劃的決定是基於多種因素。所以它包括我們與 FDA 的討論，我們已經就其開發進行了討論。此時，FDA 表示，根據迄今為止的情況，加速審批途徑尚未開放。它主要基於我們自己的效益風險評估，其中包括安全性，其中包括我們看到的低鎂血症，其中包括在某些情況下長期低鎂血症。

And then the evolving landscape of Duchenne, including the approval of ELEVIDYS. So taking all of those things together led to our decision.

然後是 Duchenne 不斷發展的格局，包括 ELEVIDYS 的批准。因此，綜合考慮所有這些因素，我們做出了決定。

Let me just contextualize all of this just to remind folks. So commencing really in February of 2018, the FDA had confirmed that it had a precedent for the use of the accelerated approval pathway for PMOs, and that precedent was really rested on two things. It's obviously rested on the value of dystrophin reduction for Duchenne muscular dystrophy. But it also rests as well on the safety of the morpholino oligonucleotide PMOs, and that safety profile itself is very laudable. Second, really, there's almost none.

讓我將所有這些都放在上下文中以提醒人們。因此，從 2018 年 2 月開始，FDA 已確認其有針對 PMO 使用加速審批途徑的先例，而該先例實際上是基於兩件事。顯然，這取決於抗肌肉營養不良蛋白減少對杜氏肌肉營養不良症的價值。但它也依賴嗎啉代寡核苷酸 PMO 的安全性，而這種安全性本身就非常值得稱讚。其次，實際上，幾乎沒有。

When one attaches a delivery moaty to a PMO, then you will change that safety profile potentially in that risk-benefit analysis. And I think the agency wasn't comfortable with the concept of accelerated approval in light of this change. And then of course we independently did a risk-benefit analysis and concluded that the program shouldn't continue.

當一個人將交付護城河附加到 PMO 時，您將在風險效益分析中潛在地改變安全狀況。我認為，鑑於這一變化，該機構對加速批准的概念感到不滿。當然，我們獨立地進行了風險收益分析，並得出結論認為該計劃不應該繼續下去。

So that's where we are. And I think this is in the -- first and foremost, it is in the benefit of the patients that we serve. And then secondly, of course, it benefits our other stakeholders as well.

這就是我們現在的情況。我認為這首先是為了我們所服務的病人的利益。其次，當然，它也有利於我們的其他利害關係人。

Andrew Tsai, Jefferies.

安德魯·蔡，杰弗里斯。

Congrats on the execution. Thanks for taking my question. So about the ELEVIDYS launch, your partner Roche made a comment about two weeks ago how 500 patients have been treated worldwide so far, including 450 in the US. So can you help us reconcile that 450 US patient number?

恭喜執行。感謝您提出我的問題。關於 ELEVIDYS 的推出，您的合作夥伴羅氏大約兩週前發表了評論，說明迄今為止全球已有 500 名患者接受治療，其中包括美國的 450 名患者。那麼您能幫助我們核對 450 名美國患者的數量嗎？

Presumably, a good chunk are in clinical trials. Even backing out those patients, we could be getting a nice implied jump in Q4 sales that could be above your Q4 guidance. So maybe help us reconcile that. Thank you.

據推測，很大一部分正在進行臨床試驗。即使排除這些患者，我們也可能會得到第四季度銷售額的隱含大幅增長，這可能會高於您的第四季度指引。所以也許可以幫助我們協調這一點。謝謝。

Yeah. Andrew, I'm not going to comment or confirm that we haven't provided those numbers like that. We're going to use revenue as our metric. And we're -- as it stands today, standing on the guidance that we've provided, previously, I mean, it certainly is the case qualitatively that we have dosed an enormous number of patients.

是的。安德魯，我不會發表評論或確認我們沒有提供這樣的數字。我們將使用收入作為衡量標準。就目前情況而言，我們站在我們之前提供的指導方針上，我的意思是，從質量上來說，我們已經給大量患者服用了藥物。

We have an extraordinary amount of experience with ELEVIDYS. Louise will have mentioned to you that we've already dosed between clinicals and some commercial 80 or so, probably more than that by now, about 80 patients that are either late ambulatory or non-ambulatory in addition to all of the other patients who dose.

我們在 ELEVIDYS 方面擁有豐富的經驗。Louise 會向您提到，我們已經在臨床和一些商業治療之間對80 名左右（可能比現在更多）進行了給藥，除了所有其他接受給藥的患者外，還有大約80 名晚期能臥床或不能臥床的患者。

And as you know, we've not seen a difference in any safety metrics. So the things that look great, the profile of the therapy looks great, and the launch is going great. So that's where we are right now with it. And we're excited to give you an update after Q4.

如您所知，我們沒有看到任何安全指標的差異。因此，事情看起來很棒，療法的概況看起來很棒，而且發布進展順利。這就是我們現在的情況。我們很高興在第四季度後向您提供最新消息。

Brian Abrahams, RBC Capital Markets.

布萊恩‧亞伯拉罕斯 (Brian Abrahams)，加拿大皇家銀行資本市場部。

Hi. This is Kevin on for Brian. Thanks for taking our questions. I just wanted to ask, can you speak to what progress you've made in conversations with payers on broader coverage policies? And maybe can you speak more to your efforts in ensuring Medicaid coverage policies? And if you can remind us what proportion of patients with DMD you estimate to be on Medicaid? Thanks a lot.

你好。這是凱文替布萊恩發言。感謝您回答我們的問題。我只是想問，您能否談談您在與付款人就更廣泛的承保政策進行對話方面取得了哪些進展？也許您可以多談談您在確保醫療補助覆蓋政策方面所做的努力嗎？您能否提醒我們，您估計接受醫療補助的 DMD 患者比例是多少？多謝。

Yeah, so it's about -- and Dallan, following my remarks, if there's anything to add or if I've made a fundamental error, you can correct me. Broadly speaking, it's about 50% commercial, 50% Medicaid, things are going very well, interactions both from a Medicaid perspective and a commercial perspective are very productive.

是的，所以這是關於——達倫，根據我的發言，如果有什麼要補充的，或者如果我犯了一個根本性的錯誤，你可以糾正我。從廣義上講，大約有50%是商業性的，50%是醫療補助，一切進展順利，從醫療補助角度和商業角度的互動都非常有成效。

And one of the things that we're really benefiting right now is a couple things. One, the amount of evidence and data that we have that supports bringing ELEVIDYS to a broad group of Duchenne patients is great and gives us a lot to talk about. The depth of the conversations that we're having with payers and the quality of those conversations is absolutely fantastic.

我們現在真正受益的事情之一是幾件事。第一，我們擁有大量證據和數據，支持將 ELEVIDYS 應用於廣泛的 Duchenne 患者，這給了我們許多值得討論的內容。我們與付款人進行的對話的深度和品質絕對是非常棒的。

And we're all benefiting from this. If one focuses down on Sarepta itself, we have become very expert over the last nearly a decade, about eight years in working with payers and gaining access to patients for our therapy.

我們都從中受益。如果專注於 Sarepta 本身，我們在過去近十年（大約八年）與付款人合作並為患者提供治療方面已經變得非常專業。

At the same time, in fairness, physicians have become increasingly more sophisticated in how to manage through the process to get kids on therapy. And payers, both Medicaid and commercial, have become far more experienced with Duchenne muscular dystrophy and how that disease works and the like, so that the entire quality of the discussions are far more productive than they may have been some eight years ago.

同時，公平地說，醫生在如何管理讓孩子接受治療的過程方面變得越來越成熟。醫療補助和商業的付款人對杜氏肌肉營養不良症以及這種疾病的發病機制等方面的經驗要豐富得多，因此討論的整體質量比大約八年前要富有成效得多。

And it's also resulting in the performance that you're seeing today, which is of course a very, very good launch which is matching the trajectory that we had imagined that we would have with all of the work that we did to prepare ourselves for this launch.

這也導致了你們今天看到的表現，這當然是一次非常非常好的發布，符合我們想像的軌跡，我們為此做好了所有準備工作發射。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

This is Tammy on for Salveen. So just on the 2Q call, I believe it was mentioned that there were some infusions that were rescheduled from 2Q to 3Q. Is it possible to quantify that impact? And more broadly, what's the latest thinking on how to think of the tail end of the launch and the peak year? Thanks so much.

這是薩爾文的塔米。因此，在第二季的電話會議上，我相信有人提到有一些輸液從第二季重新安排到了第三季。是否可以量化這種影響？更廣泛地說，關於如何看待發布的尾聲和高峰年的最新想法是什麼？非常感謝。

The first part of the question I will turn over to Dallan. The second part of the question is that what I will say to you right now is that we're going to go through a period of significant growth over the course of this decade and we will get through the prevalent population by 2030.

問題的第一部分我將交給達蘭。問題的第二部分是，我現在要對你們說的是，我們將在這十年中經歷一段顯著增長的時期，到 2030 年我們將達到人口增長的目標。

With that said, Dallan, if you want to comment a little more on Q3.

話雖如此，Dallan，如果您想對第三季度進行更多評論。

Yeah. If the question was if that impacted our performance or our guidance in any way. Remember we guided off of Q2 sales, growth off of Q2 sales, which so that was factored into our guidance and expectations for Q3 and Q4 already. So there's no real quantification of the impact of that.

是的。如果問題是這是否以任何方式影響我們的表現或我們的指導。請記住，我們以第二季的銷售為指導，以第二季的銷售為基礎進行成長，因此這已納入我們對第三季和第四季的指導和預期。因此，目前還沒有真正量化其影響。

Anupam Rama, JP

阿努潘·拉瑪，太平紳士

Just a quick one for me. You've given a little bit more details on your internal pipeline focus here in the near term. It looks like we're going to hear a little bit more at an R&D day in 2025. Just wondering how we should think about sort of the time and resources spent on the internal pipeline versus you guys doing some external business development.

對我來說只是一個快速的。您已經提供了有關近期內部管道重點的更多詳細資訊。看起來我們會在 2025 年的研發日聽到更多的消息。只是想知道我們應該如何考慮花在內部管道上的時間和資源與你們進行一些外部業務開發的時間和資源。

And I know you guys only said one question, but since it's third quarter earnings, if I could just ask if you might pre-announce at a small healthcare conference in January, that would be cool. Thanks.

我知道你們只說了一個問題，但由於這是第三季度的收益，如果我能問你們是否可以在一月份的小型醫療保健會議上預先宣布，那就太酷了。謝謝。

Okay, so first of all, thank you very much for your question, Anupam. As it relates to your first question, let me say that we're really focusing right now on two major and very important things. One of course is the launch of ELEVIDYS, which as you can see right now, hopefully is going swimmingly. And that's the result of an enormous amount of work over many years by a lot of folks.

好的，首先，非常感謝您提出問題，Anupam。由於這涉及到你的第一個問題，我想說的是，我們現在真正關注的是兩個主要且非常重要的事情。其中之一就是 ELEVIDYS 的推出，正如您現在所看到的，希望一切進展順利。這是許多人多年來大量工作的結果。

And also, in that first part is continuing performance of the PMOs, which themselves are doing very well, bringing a better life to kids, very durable, and so far not seeing any significant impacts from the launch of ELEVIDYS. So all fantastic there.

而且，第一部分是 PMO 的持續表現，它們本身做得非常好，為孩子們帶來了更好的生活，非常持久，到目前為止還沒有看到 ELEVIDYS 的推出產生任何重大影響。所以那裡一切都很棒。

The second big effort of this organization right now is advancing our internal pipeline. We're getting a lot of great traction there. There is a lot of excitement. We're going to do kind of a curtain raiser next year and really show you some of the deeper pipeline and some of the things that we're very excited about.

該組織目前的第二項重大努力是推進我們的內部管道。我們在那裡獲得了很大的吸引力。有很多興奮。明年我們將拉開帷幕，向您展示一些更深層的產品線以及一些我們非常興奮的事情。

But even in the near term, in the late stage, you can see we are in the next few months really will be in clinical trials on three of our limb-girdle program. So that's really beginning to accelerate and we're very, very excited about that. That's what we're focused on as an organization right now.

但即使在短期內，在後期，你可以看到我們在接下來的幾個月確實將進行我們的三個肢帶計畫的臨床試驗。所以這確實開始加速，我們對此非常非常興奮。這就是我們作為一個組織目前關注的重點。

Yes, we are going to go, as Ian has said, we're going to be profitable from a GAAP and a non-GAAP basis on a go-forward basis as we have been in prior quarters now. And we're going to be cashflow positive, really starting very early next year. And that gives us some opportunities to think even more broadly.

是的，正如伊恩所說，我們將繼續從 GAAP 和非 GAAP 基礎上實現盈利，就像我們在前幾個季度所做的那樣。我們將從明年初開始實現正現金流。這給了我們一些更廣泛思考的機會。

But if you're asking us about the things that we're focusing on right this minute right now, it's ensuring the success of our four approved therapies, including the launch of ELEVIDYS, and really advancing and accelerating our internal pipeline, which we are excited about.

但如果你問我們目前正在關注的事情，那就是確保我們四種已批准療法的成功，包括 ELEVIDYS 的推出，並真正推進和加速我們的內部管道，我們正在興奮於。

Now, on the second one, I'm not going to make any commitments as we stand here right now. We have had, as you know, a history of doing some pre-announcements at that conference in January, but of course we'll wait and see in January what we do there, but we will likely be consistent with history. That's where we are.

現在，關於第二個問題，當我們站在這裡時，我不會做出任何承諾。如您所知，我們有在 1 月的會議上發布一些預先公告的歷史，但我們當然會在一月份等待看看我們在那裡做了什麼，但我們很可能會與歷史保持一致。這就是我們現在的處境。

Danielle Brill, Raymond James.

丹妮爾·布里爾，雷蒙德·詹姆斯。

So by our math, there was about 20 additional patients treated in 3Q versus 2Q. And for all intents and purposes, it sounds like the launch is going great. So I guess we just thought that the step up in treatment rates could be more pronounced following the label expansion.

因此，根據我們的計算，與第二季度相比，第三季度大約有 20 名額外的患者接受了治療。無論出於何種意圖和目的，聽起來這次發布進展順利。所以我想我們只是認為標籤擴展後治療率的提高可能會更加明顯。

Can you just talk a little bit more about what you're seeing in the market and what the main bottlenecks are to getting these kids treated? Thanks.

您能否多談談您在市場上看到的情況以及讓這些孩子得到治療的主要瓶頸是什麼？謝謝。

Let me just say again -- first of all, when we talk about performance, we're going to talk in revenue as our marker. We're not going to use other metrics. And we're very, very excited about the progress of our launch, and it's going exactly to plan. And we're seeing the trajectory that we had envisioned and we spoke about a few quarters back. So everything is going fantastic.

讓我再說一次——首先，當我們談論績效時，我們將談論收入作為我們的指標。我們不會使用其他指標。我們對我們的發布進度感到非常非常興奮，而且它完全按照計劃進行。我們正在看到我們所設想的軌跡，並且我們在幾個季度前談到這一點。所以一切都很順利。

The shape of that growth is a combination broadly of three things and it always will be. Some of it is -- a piece of it is site capacity, and that's not simply a matter of getting more sites up and running. It's making sure that you have sites that are well educated, well informed, expert and that they have the ability to manage and monitor kids post-dosing so that we always have this extraordinarily positive safety and efficacy profile that we have today with ELEVIDYS at least from my perspective.

這種成長的形式大致上是三件事的結合，而且永遠都是這樣。其中一部分是網站容量，這不僅僅是建立和運行更多網站的問題。它確保您擁有受過良好教育、消息靈通、專家的網站，並且他們有能力管理和監測兒童用藥後的情況，以便我們始終擁有這種非常積極的安全性和有效性概況，至少是我們今天在ELEVIDYS上擁有的從我的角度來看。

The second one of course is just manufacturing and batch release and making sure that we're thoughtful about that. And the third one is payer interactions, which are going great. Both from a Medicaid perspective and a commercial perspective, everything's going very well.

第二個當然只是製造和批量發布，並確保我們對此深思熟慮。第三個是付款人互動，進展順利。無論是從醫療補助的角度或商業的角度來看，一切都進展順利。

So things are tracking exactly as we had hoped. And that's why we're able to reiterate the guidance that we provided previously, both about Q4 and our guidance for 2025, $3 billion is the mean of that, and our long-term forecast and the fact that we will be going through a period of multiple years of significant growth as we, over the course of this decade, treat the prevalent population, even as we are also treating the incident population now and deeply into the future.

所以事情的進展正如我們所希望的那樣。這就是為什麼我們能夠重申我們之前提供的指導，包括第四季度和 2025 年的指導，30 億美元是其中的平均值，以及我們的長期預測和我們將經歷一段時期的事實在這十年中，我們在治療流行人群的同時，也正在治療現在和未來的發病人群，因此我們的治療取得了多年的顯著增長。

Ellie Merle, UBS.

艾莉·梅爾，瑞銀。

Can you just elaborate a bit more on your comments on site capacity just now, just the latest that you're seeing? You mentioned you're seeing ample site capacity, but I guess how many sites dose patients in 3Q, and I guess how dispersed or concentrated has this dosing been across the sites? Thanks.

您能否詳細說明您剛才對網站容量的評論，只是您所看到的最新情況？您提到您看到了充足的站點容量，但我猜想第三季度有多少站點為患者提供了劑量，我猜這些站點之間的劑量分佈有多分散或集中？謝謝。

Yeah, so we have about -- so I'll just say broadly, we have about 75 sites. They might modestly increase over time, reactively. And Dallan can provide answer to us on as we sit here today, what percentage of those sites have actually been dosing sites.

是的，我們大約有——所以我只是泛泛地說，我們大約有 75 個站點。隨著時間的推移，它們可能會被動地適度增加。當我們今天坐在這裡時，達蘭可以向我們提供答案，即這些網站中有多少百分比實際上是劑量網站。

Yeah, the vast majority of centers have those patients. And we really don't get into specifics quarter to quarter on how concentrated these sites are. So as Doug had said earlier, we're focusing our guidance on revenue, net product revenue.

是的，絕大多數中心都有這些病人。我們確實沒有逐季度詳細了解這些網站的集中程度。正如道格之前所說，我們的指導重點是收入、淨產品收入。

Gil Blum, Needham & Co.

吉爾布魯姆，李約瑟公司

Hey, guys. Thanks for taking our question and congrats on the progress. So now that 5051 seems out, are there any thoughts for life cycle management of the PMOs? And it kind of feels like Sarepta is strategically moving away from exon skippers. thank you.

嘿，夥計們。感謝您提出我們的問題並祝賀我們的進展。那既然5051已經出來了，對於PMO的生命週期管理有什麼想法嗎？感覺像是 Sarepta 正在戰略性地遠離外顯子隊長。謝謝。

First, I don't want to suggest for a moment that we're moving away from exon skippers. And we do have a lot of thoughts on other modalities for exon skipping. We're not in a position right now to discuss them in any detail, but we are constantly looking at opportunities to enhance the benefit that our therapies provide to patients.

首先，我暫時不想建議我們放棄外顯子隊長。我們確實對外顯子跳躍的其他方式有很多想法。我們現在無法詳細討論它們，但我們一直在尋找機會來增強我們的療法為患者提供的益處。

The reason that we are not moving away from exon skipping right now, even though we are very excited both about ELEVIDYS and what ELEVIDYS can do, and also the rest of our deep pipeline, including cardiomyopathies and CNS and other neuro muscular as well. The reason we're still excited about PMOs is they're doing an enormous amount of good right now. So that's an important thing to consider.

我們現在還沒有放棄外顯子跳躍的原因是，儘管我們對 ELEVIDYS 和 ELEVIDYS 的功能以及我們的其他深層管道（包括心肌病變、中樞神經系統和其他神經肌肉疾病）都非常興奮。我們仍然對 PMO 感到興奮的原因是他們現在正在做大量的好事。所以這是一個需要考慮的重要事情。

The PMOs make a small amount of dystrophin, but a small amount of dystrophin is very meaningful as we have recently published the real-world evidence on EXONDYS which will presumably be the same answer for VYONDYS and AMONDYS over time as their experience are really tremendous. We're seeing multiple years out of a wheelchair, multiple years of better mortality, multiple years off event, reductions in emergency room visits and the like.

PMO 會產生少量的肌肉營養不良蛋白，但少量的肌肉營養不良蛋白非常有意義，因為我們最近發布了EXONDYS 的真實世界證據，隨著時間的推移，這可能與VYONDYS 和AMONDYS 的答案相同，因為他們的經驗確實非常豐富。我們看到多年不再使用輪椅，死亡率多年降低，事件減少多年，急診室就診次數減少等。

So we remain very excited about the benefit that our PMOs can safely provide to patients. And that's one of the things that's really great about the PMOs and that is that they are not only are providing a really significant benefit to patients, but the safety profile is great. And that's why one should remember, even as we think about our own pipeline and we think about others, that while we're always ambitious, the bar for beating the PMOs is very high and the road to any approval for an alternative to our PMOs on the exon skipping side is very long.

因此，我們對我們的 PMO 能夠安全地為患者提供的好處仍然感到非常興奮。這是 PMO 真正偉大的事情之一，那就是它們不僅為患者提供了真正顯著的好處，而且安全性也很好。這就是為什麼人們應該記住，即使我們考慮我們自己的管道並考慮其他管道，雖然我們總是雄心勃勃，但擊敗 PMO 的門檻非常高，而且要獲得批准替代我們的 PMO 的道路外顯子跳躍側很長。

So I don't want to suggest for a minute that we're in any way less excited about our PMOs. We're excited every week that a patient gets an infusion and benefits from either EXONDYS or VYONDYS or AMONDYS, and we will remain that way. And I think one of the things that I'm excited about right now, particularly during the launch and the fact that we're not seeing a ton of cannibalization, is that there is a long road for the PMOs. I think they're going to be very durable.

因此，我暫時不想表明我們對 PMO 不那麼興奮。每週，當患者接受輸液並從 EXONDYS 或 VYONDYS 或 AMONDYS 中受益時，我們都會感到興奮，我們將保持這種狀態。我認為我現在感到興奮的事情之一，特別是在發布期間，以及我們沒有看到大量蠶食的事實是，專案管理辦公室還有很長的路要走。我認為它們會非常耐用。

Ritu Baral, TD Cowen.

裡圖·巴拉爾，TD·考恩。

I wanted to ask about forward guidance, especially given the insight you guys have on basically revenues. Doug, you mentioned three to five months time to fill. Just given where you guys are notified about when a patient is seeking reimbursement and when you have to make their kit, ship the kit, et cetera, and when they're dosed.

我想詢問有關前瞻性指引的問題，特別是考慮到你們對基本收入的見解。道格，你提到需要三到五個月的時間來填補。只要告訴你們，當病人尋求報銷時，當你必須製作他們的工具包、運送工具包等等，以及他們何時服藥時，你們會收到通知。

Are we going to, one, are we going to continue to get some pretty granular guidance as you've given? And two, given the healthy beat congratulations this quarter, what sort of swing factors should we be thinking about despite that three- to five-month insight, logistical swing factors beyond Ian's tendency to give conservative guidance?

我們是否會，第一，我們是否會繼續獲得您所提供的一些非常詳細的指導？第二，鑑於本季度的健康節拍祝賀，儘管有三到五個月的洞察力，但後勤波動因素超出了伊恩給出保守指導的傾向，我們應該考慮什麼樣的波動因素？

Look, of course, it's always our goal to provide reasonable and accurate guidance, but guidance that we're very comfortable with. And we will continue to ensure that we are comfortable with the guidance that we've provided. And if that makes us seem conservative, I'm probably proud of that.

當然，提供合理、準確的指導始終是我們的目標，也是我們感到非常滿意的指導。我們將繼續確保我們對所提供的指導感到滿意。如果這讓我們顯得保守，我可能會為此感到自豪。

We have an enormous amount of insight as you know, about not only broadly about Duchenne muscular dystrophy and FDA prevalence, but all the way down to things like start forms and the like. And that does provide us with a lot of confidence as we think about forecasting and guidance and the like.

如您所知，我們擁有大量的見解，不僅廣泛涉及杜氏肌肉營養不良症和 FDA 盛行率，而且一直深入到起始表格等問題。當我們考慮預測和指導等時，這確實為我們提供了很大的信心。

And with that said, as we sit here today, notwithstanding our very positive, in my view, and significant beat, we're not going to update our guidance at this moment. And we'll talk again probably at JPMorgan if we do pre-announce at JPMorgan about 2025.

話雖如此，當我們今天坐在這裡時，儘管我認為我們非常積極並且取得了重大進展，但我們目前不會更新我們的指導。如果我們確實在摩根大通預先宣布 2025 年的消息，我們可能會在摩根大通再次討論。

Joseph Schwartz, Leerink Partners.

約瑟夫‧施瓦茨，Leerink Partners。

I have a question about the next MRI study you plan to do. I'm wondering how will this differ from the MRI data that you presented at WMS. And will you be using gadolinium enhancement to evaluate tissue characteristics like edema and fibrosis, per dosing, and will you evaluate global longitudinal strain?

我對您計劃進行的下一次 MRI 檢查有疑問。我想知道這與您在 WMS 上提供的 MRI 數據有何不同。您是否會使用钆增強來評估每次給藥時的組織特徵，例如水腫和纖維化，並且您會評估整體縱向應變嗎？

Louise?

路易絲？

Sure, so from the EMARK study, the longer-term data will be following the patients over time and then that will be compared if there's a wealth of natural history data compared to natural history since all patients have been dosed now. So they'd be compared to their baseline and then to natural history.

當然，從 EMARK 研究來看，長期數據將隨著時間的推移追蹤患者，然後如果有大量的自然史數據與自然史相比，就會進行比較，因為所有患者現在都已接受給藥。因此，他們將與基線進行比較，然後與自然歷史進行比較。

So we'll continue to do MRI, MRS. And T2 gives the early signal of the inflammation and edema that you noted. So that's a precursor to changes that you would see by MRI and MRS. So we'll continue to use those three measurements and strain as a portion of the MRI results.

所以我們會繼續做MRI、MRS。T2 給出了您注意到的發炎和水腫的早期信號。這是 MRI 和 MRS 所看到的變化的先兆。因此，我們將繼續使用這三個測量值和應變作為 MRI 結果的一部分。

Kostas Biliouris, BMO Capital Markets.

Kostas Biliouris，BMO 資本市場。

Thanks for taking our questions and congrats on the quarter. One question from us on manufacturing, given the 300% quarter-over-quarter growth of ELEVIDYS sales ex-US and potential further acceleration with upcoming approvals in Europe and Japan, can you comment on your manufacturing capacity to meet this high level of demand?

感謝您回答我們的問題並祝賀本季。我們提出一個關於製造的問題，鑑於ELEVIDYS 在美國以外的銷售額環比增長300%，並且隨著歐洲和日本即將獲得批准，可能會進一步加速，您能否評論一下你們滿足這一高水平需求的製造能力？

And a follow up on the same topic. Can you clarify whether the suspension manufacturing will be only with Thermo Fisher, or there is optionality to do that with Catalent as well? Thank you.

以及同一主題的後續行動。您能否澄清一下懸吊的製造是否僅由 Thermo Fisher 進行，還是也可以選擇與 Catalent 一起進行？謝謝。

Yeah. Thank you very much for your questions, Kostas. First, as relates to the first part of your question, we're very comfortable with our forecast and our manufacturing to supply. We're in a very good position from the manufacturing perspective to serve ours and our partners needs.

是的。非常感謝您的提問，科斯塔斯。首先，關於你問題的第一部分，我們對我們的預測和我們的供應製造感到非常滿意。從製造角度來看，我們處於非常有利的地位，可以滿足我們和合作夥伴的需求。

As relates to suspension, to remind everyone, things are going very well with suspension right now. We're in engineering runs, both in 500 liter and 2,000 liters, and we're going to start our bridging steady next year, assuming everything goes well, and we believe it will. And we have not made a decision as it stands today on who we will use as a commercial supplier for suspension. So that's an issue we're continuing to ponder and evaluate.

關於暫停，提醒大家，目前暫停的情況進展順利。我們正在進行 500 公升和 2,000 公升的工程運行，假設一切順利，我們將於明年開始穩定的過渡，我們相信會的。目前我們還沒有決定將使用誰作為暫停的商業供應商。所以這是我們繼續思考和評估的問題。

Brian Skorney, Baird.

布萊恩·斯科尼，貝爾德。

Actually, my question is on redosing. And I guess, when can we think about seeing initial data here from either the [Freestyle] study or the Hansa collaboration study you're planning to go about? And how do you kind of think about clinical development here? Do you focus on patients who had received prior ELEVIDYS but had an adequate dystrophin response? Do you target naive patients with higher rh74 serology?

其實我的問題是關於重做。我想，我們什麼時候可以考慮查看您計劃進行的 [Freestyle] 研究或 Hansa 合作研究的初始數據？您如何看待這裡的臨床開發？您是否關注先前接受過 ELEVIDYS 但具有足夠抗肌肉營養不良蛋白反應的患者？您是否針對 rh74 血清學程度較高的初治患者？

And do you have access to [Justin Implodais] in your Hansa deal or is HNSA-5487 next-gen cleaver included in that? Thanks.

您是否可以在 Hansa 交易中使用 [Justin Implodais]，或者其中是否包含 HNSA-5487 下一代切肉刀？謝謝。

All right. I'm going to turn this to Louise. Before I do, I want to make sure I have a clarification here. And Brian, thank you very much for your question and the opportunity to clarify.

好的。我要把這個轉給路易絲。在此之前，我想先澄清一下。Brian，非常感謝您提出問題並給我機會進行澄清。

So there is definitely an opportunity down the road to use some modality to either cleave or clear neutralizing antibodies in a manner that might allow for redosing. And we're very excited about that potential.

因此，未來肯定有機會使用某種方式以允許重新給藥的方式裂解或清除中和抗體。我們對這種潛力感到非常興奮。

But just so we're clear, as we sit here today, that is not actually the goal of our near-term studies. Our near-term studies are intended to do something slightly different, which is to clear or cleave antibodies that have been acquired by a Duchenne patient through environmental exposure to put them in a position where we could dose them with ELEVIDYS, and that would provide an opportunity for another 15% or so of Duchenne patients who would right now be screened out to actually get the opportunity to have ELEVIDYS.

但正如我們今天坐在這裡一樣，我們很清楚，這實際上並不是我們近期研究的目標。我們的近期研究旨在做一些略有不同的事情，即清除或裂解 Duchenne 患者透過環境暴露獲得的抗體，將其置於我們可以使用 ELEVIDYS 給藥的位置，這將提供為另外15% 左右的Duchenne患者提供機會，他們現在將被篩選出來，真正有機會接受ELEVIDYS。

And with that, Louise, if you want to provide some color on Brian's questions.

路易絲，如果你想對布萊恩的問題提供一些解釋的話。

Sure. So the question about when we'll have data for both studies. We'll have safety and expression data in early 2025 on the initial cohort. And really that data will inform us for anything we do in the future with regards to a potential study for redosing.

當然。所以問題是我們什麼時候才能獲得這兩項研究的數據。我們將在 2025 年初獲得初始隊列的安全性和表達數據。事實上，這些數據將為我們未來所做的有關重劑量潛在研究的任何事情提供資訊。

As Doug mentioned, that's not the goal right now, but we've been positioning ourselves to be ready. In case we do, we've shown good data in non-human primates. So the challenge for redosing is much higher antibody levels. And so this data from these preexisting antibody charts will be critical in seeing how far we can go and how we might design a study if we were to do so with redosing.

正如道格所提到的，這不是現在的目標，但我們一直在做好準備。如果我們這樣做的話，我們已經在非人靈長類動物中展示了良好的數據。因此，重新給藥的挑戰是更高的抗體水平。因此，這些預先存在的抗體圖表的數據對於了解我們能走多遠以及如果我們要重新給藥的話我們如何設計一項研究至關重要。

And then Brian, to answer your final question, we have a right of first negotiation on a next-generation therapy.

然後布萊恩，回答你的最後一個問題，我們有權就下一代療法進行優先談判。

Kristen Kluska, Cantor Fitzgerald.

克里斯汀·克魯斯卡，坎托·費茲傑拉。

Hi. Congratulations on the revenue beat. You seem to not be getting a whole lot of credit for the limb-girdle portfolio. So I wanted to ask if you could remind us about the number of patients you expect could be identified around the time of these launches and how we should be thinking about that market opportunity. Thank you.

你好。恭喜收入突破。您似乎並沒有因為肢帶投資組合而獲得太多讚譽。因此，我想問您是否可以提醒我們，您預計在這些產品發布期間可以識別出多少患者，以及我們應該如何考慮該市場機會。謝謝。

Yeah, that's a great question. Thank you very much. And it's a particularly poignant question now because we're really starting to make traction and move fast on our limb-girdle portfolio.

是的，這是一個很好的問題。非常感謝。現在這是一個特別尖銳的問題，因為我們確實開始在我們的肢帶產品組合上發揮牽引力并快速前進。

Broadly speaking, let me say that the limb-girdle portfolio we have today is about 70% of the opportunity of Duchenne muscular dystrophy, so quite significant. And if you think about the size of Duchenne muscular dystrophy, maybe in the 12,000, 15,000 -- probably more like 12,000 range in the United States, then you can see this is a massive opportunity to do good and do well by our investors at the same time.

從廣義上講，我想說的是，我們今天擁有的肢帶組合大約有 70% 的杜氏肌肉營養不良症機會，因此相當重要。如果你考慮一下杜氏肌肉營養不良症的規模，也許在12,000、15,000 之間——在美國可能更接近12,000 範圍，那麼你就會發現，這是一個巨大的機會，可以讓我們的投資者在世界範圍內做好事。

Our near-term programs, [CYBERGLI-CAN], are themselves actually quite significant. They're something in the range of 25% or more of the Duchenne muscular dystrophy, and we're going to be in late-stage development with all three of those programs in the coming few months. So there's a big opportunity that I think people will start focusing on as they clear and get more excited about and more confident about the launch of ELEVIDYS, and hopefully this quarter is helping to that.

我們的近期計劃 [CYBERGLI-CAN] 本身實際上非常重要。它們佔杜氏肌肉營養不良症的 25% 或更多，我們將在未來幾個月內對這三個項目進行後期開發。因此，我認為人們會開始專注於一個巨大的機會，因為他們對 ELEVIDYS 的推出變得更加興奮和自信，希望本季能對此有所幫助。

Biren Amin, Piper Sandler.

比倫·阿明，派珀·桑德勒。

Can you maybe just talk about the split of patients that you saw in the third quarter across ambulatory versus non-ambulatory from a commercial standpoint? And what type of access are you seeing across both groups? Thanks.

您能否從商業角度談談您在第三季度看到的門診患者與非門診患者的劃分？您在這兩個群體中看到了什麼類型的訪問？謝謝。

Yeah, we're not going to provide a granular breakdown of that, but I can give you some broad qualitative color. I mean, one of the things that one would anticipate, that we anticipated and others have anticipated at launch is that there may be a bias in favor of ambulatory patients over non-ambulatory patients at launch. And certainly, that is the case, but it isn't probably as significant as some may have imagined.

是的，我們不會提供詳細的細節，但我可以給你一些廣泛的定性資訊。我的意思是，人們在推出時所預期的、我們預期的和其他人預期的一件事是，在啟動時可能會存在有利於流動患者而不是非流動患者的偏見。當然，情況確實如此，但也可能不像某些人想像的那麼重要。

We're seeing a very significant percentage of start forms for late-ambulatory, non-ambulatory patients, which is fantastic. I think that as more information comes out about the number of patients that have been dosed in the late-ambulatory, non-ambulatory setting and the safety profile that we're seeing there, which is the same as the ambulatory patients, it's only going to increase that awareness and excitement.

我們看到晚期能臥床、不能臥床的患者的起始表格比例非常高，這太棒了。我認為，隨著更多關於在晚期門診、非門診環境中接受給藥的患者數量以及我們在那裡看到的安全狀況（與門診患者相同）的信息的出現，它只會繼續下去增加這種意識和興奮感。

We've already dosed kids in the mid-20s who are obviously non-ambulatory and we have start forms of men in their late 30s, which is very, very advanced for Duchenne muscular dystrophy.

我們已經對 20 多歲的明顯不能行走的孩子進行了給藥，並且我們已經開始對 30 多歲的男性進行了給藥，這對杜氏肌肉營養不良症來說是非常非常晚期的。

So while there is, as we have guided to and anticipated, there is some bias towards the ambulatory versus non-ambulatory in the very early days, there is a very significant percentage of non-ambulatory, and we're quite confident that's going to continue to increase over time.

因此，正如我們所指導和預期的那樣，雖然在早期對流動型與非流動型存在一些偏見，但非流動型的比例非常大，我們非常有信心這將隨著時間的推移繼續增加。

Dallan, is there anything about that that I've missed?

Dallan，有什麼我錯過的嗎？

Gavin Clark-Gartner, Evercore ISI.

Gavin Clark-Gartner，Evercore ISI。

I just wanted to ask on the ESSENCE confirmatory trial, is the latest guidance still for data in 2026? I'm just looking at the trial page and it still notes the primary completion date is next week actually.

我只是想問ESSENCE驗證性試驗，最新的指導意見還是2026年的數據嗎？我只是在查看試用頁面，它仍然指出主要完成日期實際上是下週。

And just more broadly for this trial, do you have any sense what the requirements to actually pull these drugs off the market maybe, especially in light of the fact we haven't really heard anything following the Viltepso results. Thanks.

更廣泛地說，對於這次試驗，您是否知道真正將這些藥物撤出市場的要求是什麼，特別是考慮到我們還沒有真正聽到任何關於 Viltepso 結果的消息。謝謝。

Well -- first of all, Louise, correct me if I'm wrong, the readout for ESSENCE is in 2026, correct?

好吧——首先，Louise，如果我錯了，請糾正我，ESSENCE 的讀數是 2026 年，對嗎？

That's correct.

這是正確的。

Yeah, and then as it relates to the standard for evaluating a therapy and whether it should be removed from the market is based on the totality of evidence. When all of the evidence is in on the therapy, the FDA will look at the totality of all of the evidence associated with that therapy, including study results, including trends in the study results, including presumably the information like the real-world evidence that we've gathered with respect to the PMOs, which has been very positive so far, and then we'll make a decision. It won't be a yes or no based on one single trial that is in the stand.

是的，因為它涉及評估一種療法的標準以及是否應該將其從市場上移除是基於證據的完整性。當所有證據都在治療上時，FDA 將審查與該治療相關的所有證據的整體，包括研究結果，包括研究結果的趨勢，大概包括諸如現實世界證據之類的信息我們已經就項目管理辦公室收集了意見，到目前為止，情況非常積極，然後我們將做出決定。不會根據展台上的一項試驗來做出「是」或「否」的結論。

Leo Watson, Mizuho.

裡奧·沃森，瑞穗。

Hi, this is Leo on for Uy. Congrats on the strong quarter and thanks for taking our question. How are you thinking about the competitive dynamics in the exon skipping business given the recent competitor data readouts and the discontinuation of the PPMO? And while you expect no material cannibalization through '25, we're just curious on how you're thinking about cannibalization going forward in the long term. Thanks.

大家好，我是 Uy 的 Leo。恭喜季度的強勁表現，並感謝您提出我們的問題。鑑於最近的競爭對手數據讀數和 PPMO 的終止，您如何看待外顯子跳躍業務的競爭動態？雖然您預計到 25 年不會出現實質的蠶食，但我們只是好奇您如何考慮長期的蠶食。謝謝。

Let me answer the second question first. So we don't think we'll see net cannibalization over the course of 2025. Remember, we also have ex-US sales of the PMOs, and those won't be in the near term, at least, subject to any cannibalization.

我先回答第二個問題。因此，我們認為 2025 年不會出現淨蠶食。請記住，我們也有 PMO 在美國以外的銷售，這些銷售至少在短期內不會受到任何蠶食。

We do model cannibalization after '25. How significant, if at all, that will be is something we're going to watch and monitor. But we have some reason to believe that these therapies are going to be very durable, certainly on a net basis over this entire decade. But we'll see how that goes post-'25.

我們在 25 年後進行模型蠶食。如果有的話，這將是多麼重要，這是我們將要觀察和監控的事情。但我們有理由相信這些療法將非常持久，尤其是在整個十年的淨基礎上。但我們會看看 25 年後情況會如何。

As relates to competition, I should note that we're not very focused on competition right now. There is no one near us today, either on the PMOs or, you know, certainly on ELEVIDYS. And I will not comment on other folks' programs, and I wish them well.

就競爭而言，我應該指出，我們現在不太關注競爭。今天我們附近沒有人，無論是在 PMO 上，還是在 ELEVIDYS 上。我不會評論其他人的節目，我祝他們一切順利。

One of the things I do want to point out as it relates to the PMOs is that how much good those PMOs are doing today. There was an open issue about that perhaps in late 2016 when EXONDYS was approved, the eteplirsen, but the real-world evidence has been really supportive. You can see it in the compliance rates for these therapies. They're doing an enormous amount of good with a really, really laudable safety profile.

我確實想指出的與 PMO 有關的一件事是，這些 PMO 今天做得有多好。也許在 2016 年底 EXONDYS 獲得批准時，存在一個懸而未決的問題，即 eteplirsen，但現實世界的證據確實具有支持性。您可以從這些療法的依從性中看到這一點。他們以非常非常值得稱讚的安全狀況做了很多好事。

And so the one thing I would say is that when we think about the PMOs and we think about competition, one ought to remember that the bar to overachieve from both an efficacy and safety perspective for the PMOs is a very high bar. And the road for even getting to clinical data that would allow one to think about approval is a very long one. This is not -- this requires one to go exon by exon over a very long period of time.

因此，我要說的一件事是，當我們考慮 PMO 並考慮競爭時，我們應該記住，從功效和安全角度來看，PMO 取得超額成績的門檻非常高。甚至獲得臨床數據來考慮批准的道路也是漫長的。這不是——這需要一個人在很長一段時間內逐個外顯子。

So I wish these folks well. I think that they have a high bar and a long road to get to the right place.

所以我祝福這些人一切順利。我認為他們有很高的標準和很長的路要到達正確的地方。

Sami Corwin, William Blair.

薩米·科溫，威廉·布萊爾。

Congrats on the quarter and thanks for taking my question. Looking ahead to a potential launch in limb-girdle, do you expect any synergies between LGMD and ELEVIDYS in terms of sale reps or treatment centers? And then with the discontinuation of 5051, could any cost savings there be used to accelerate the development of any of those limb-girdle programs? Thanks.

恭喜本季度，感謝您提出我的問題。展望肢體腰帶領域的潛在推出，您是否期望 LGMD 和 ELEVIDYS 在銷售代表或治療中心方面產生協同效應？那麼，隨著 5051 的停產，節省的成本是否可以用來加速這些肢帶計畫的開發？謝謝。

Well, there's a -- in a way, yes and yes to both of your questions. Is there synergy between a limb-girdle launch and what we've done with ELEVIDYS? 100%. Absolutely. It's going to be very, very synergistic. There'll be nuanced things we need to do in advance to make sure we're very successful. But we have a very seasoned group of folks that know how to service the rare disease community and the neuromuscular community and gain access and reimbursement and to focus on distribution.

嗯，在某種程度上，你的兩個問題都是肯定的。肢帶發布與我們對 ELEVIDYS 所做的事情之間是否存在協同作用？100%。絕對地。這將是非常非常協同的。我們需要提前做一些細緻的事情，以確保我們非常成功。但我們有一群經驗豐富的人，他們知道如何為罕見疾病社區和神經肌肉社區提供服務，獲得訪問和報銷，並專注於分配。

It's a fascinating thing to consider that the group that launched EXONDYS back in late 2016, that have become so expert. 80% of those folks remain here with Sarepta today. So yes, there'll be a lot of really nice synergy. And really frankly, synergy at the therapy level as well. I would remind folks that these limb-girdle programs that we're talking about share the same capsid so they will really be standing on the shoulders of the safety profile of ELEVIDYS. And the same promoter as ELEVIDYS, so the productivity of these therapies is uh standing on the shoulders of ELEVIDYS.

考慮到早在 2016 年底推出 EXONDYS 的團隊已經變得如此專業，這是一件令人著迷的事情。如今，其中 80% 的人仍留在 Sarepta。所以，是的，將會產生很多非常好的協同作用。坦白說，治療層面上也有協同作用。我想提醒人們，我們正在談論的這些肢帶項目共享相同的衣殼，因此它們實際上是站在 ELEVIDYS 安全性的肩膀上。而且和 ELEVIDYS 是同一個啟動子，所以這些療法的生產力呃是站在 ELEVIDYS 的肩膀上。

And then as relates to 5051, I don't want to suggest that we can accelerate the plans based on the cost savings from 5051 only, because we're already doing everything we can to move these as fast as possible and you're seeing it in the progress that we've made and announced in this earnings call. But certainly, there will be some cost savings from 5051 that we get to use to focus back down into research and development and advance our program, including our pipeline, which we're very excited to talk about next year.

然後，就 5051 而言，我不想建議我們僅根據 5051 節省的成本來加快計劃，因為我們已經盡一切努力盡快推進這些計劃，你會看到這是我們在本次財報電話會議中取得並宣布的進展。但當然，5051 將會節省一些成本，我們可以利用這些成本重新專注於研發並推進我們的計劃，包括我們的管道，我們很高興明年談論這一點。

Michael Wolf, Morgan Stanley.

麥可沃爾夫，摩根士丹利。

Hi, this is Rohit from Mike. Thanks for taking our questions. Since we're at the inflection point for ELEVIDYS sales, can you provide any color on early 4Q trends and how they're tracking versus expectations? Thanks.

大家好，我是麥克的羅希特。感謝您回答我們的問題。由於我們正處於 ELEVIDYS 銷售的拐點，您能否提供有關第四季度早期趨勢的任何資訊以及它們與預期的追蹤情況如何？謝謝。

We're not going to do that right now. We reiterated the guidance that we've provided previously. Notwithstanding that some appear to have criticized us for being conservative. We're standing by our guidance for Q4, and we are reiterating our guidance for 2025, which I would remind you, is a very significant $3 billion, two-thirds of which will come from ELEVIDYS and one-third of which will come from our three approved PMOs. So we're feeling very good about where we are as an organization and very consistent with all of our internal forecast over the last year or so.

我們現在不打算這樣做。我們重申了先前提供的指引。儘管有些人似乎批評我們保守。我們堅持對第四季度的指導，並重申我們對2025 年的指導，我想提醒您的是，這是一個非常重要的30 億美元，其中三分之二將來自ELEVIDYS，其中三分之一將來自我們批准的三個專案管理辦公室。因此，我們對我們作為一個組織的現狀感覺非常好，並且與我們過去一年左右的所有內部預測非常一致。

Thank you. I would now like to hand the conference back to Doug Ingram for closing remarks.

謝謝。現在我想將會議交還給道格·英格拉姆（Doug Ingram）進行閉幕致詞。

Well, thank you, all, very much for your very insightful questions and for spending time with us this evening. We've had a very positive quarter from our perspective. The ELEVIDYS launch is going swimmingly. The PMOs are performing very well.

好吧，非常感謝大家提出非常有見地的問題，並今晚與我們共度時光。從我們的角度來看，我們度過了一個非常積極的季度。ELEVIDYS 的發布進展順利。PMO 的表現非常出色。

And we're really starting to see a lot of traction in our pipeline. And we're getting very excited about our pipeline generally, but we're very excited about our late-stage limb-girdle programs as well which are moving into what will be the clinical trials that can support the approval of those therapies as well. And as one commenter made today and I agree with, I don't think there has been enough attention spent on the limb-girdles or the opportunity there both to do good for some patients who really need us and do well by the investors who stand by us.

我們確實開始看到我們的管道有很大的吸引力。總的來說，我們對我們的管道感到非常興奮，但我們對我們的後期肢帶計畫也非常興奮，這些計畫正在進入臨床試驗，也可以支持這些療法的批准。正如今天一位評論者所說的那樣，我同意這一點，我認為人們沒有對肢帶或那裡的機會給予足夠的關注，既可以為一些真正需要我們的患者帶來好處，也可以為那些堅持不懈的投資者帶來好處。

I look forward to keeping you all up to date and talking to you about the fourth-quarter performance when we announce fourth-quarter performance next year. Thank you all very much.

當我們明年宣布第四季業績時，我期待向大家通報最新情況並與大家討論第四季的業績。非常感謝大家。

This concludes today's conference call. Thank you for participating. 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。