Sarepta Therapeutics Inc (SRPT) 2023 Q2 法說會逐字稿

Good afternoon, and welcome to the Sarepta Therapeutics Second Quarter 2023 Earnings Call. (Operator Instructions) As a reminder, today's program is being recorded. At this time, I'll turn the call over to Francesca Nolan, Executive Director, Investor Relations and Corporate Communications. Please go ahead.

下午好，歡迎參加 Sarepta Therapeutics 2023 年第二季財報電話會議。 （操作員指示）提醒一下，今天的節目正在錄製中。此時，我會將電話轉給投資者關係和企業傳播部執行董事 Francesca Nolan。請繼續。

Thank you, Jonathan, and thank you all for joining today's call. Earlier this afternoon, we released our financial results for the second quarter of 2023. The press release is available on our website at sarepta.com, and our 10-Q was filed with the Securities and Exchange Commission this afternoon.

謝謝喬納森，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 2023 年第二季度的財務業績。新聞稿可在我們的網站 sarepta.com 上獲取，我們的 10-Q 報告已於今天下午向美國證券交易委員會提交。

Joining us on the call today are Doug Ingram, Ian Estepan, Dallan Murray and Dr. Louise Rodino-Klapac.

今天加入我們電話會議的有 Doug Ingram、Ian Estepan、Dallan Murray 和 Louise Rodino-Klapac 博士。

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 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, the results of operations and trading prices for Sarepta's common stock.

正式發言後，我們將開始問答環節。我想指出的是，在這次電話會議中，我們將做出一些前瞻性聲明。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 forward-looking statements, including any financial projections provided today based on subsequent events or circumstances. 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?

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前瞻性聲明的任何義務，包括今天根據後續事件或情況提供的任何財務預測。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, Fran. Good afternoon, and thank you for joining our second quarter 2023 financial results conference call. The second quarter of this year was perhaps the most consequential period in the long consequential history of Sarepta. For families living with Duchenne, it was far more than that still. Buddy Cassidy, living with Duchenne and an Elevates Advisory Committee member, shared the collective view of the Duchenne community on the June approval in words far more eloquent than I could possibly muster. As Buddy said and I quote, "There is more to do. But now let us pause and bask in the glow of our achievement. Let us bask in gratitude. Let us pause in celebration. Let us watch as dawn rises and brings in the day." In May of this year, the FDA held an advisory committee meeting on our gene therapy SRP-9001, now called ELEVIDYS. With a majority vote, the advisory committee recommended the approval of ELEVIDYS for the treatment of ambulatory patients with Duchenne muscular dystrophy.

謝謝你，弗蘭。下午好，感謝您參加我們的 2023 年第二季財務業績電話會議。今年第二季可能是 Sarepta 漫長歷史中最重要的時期。對於與杜興住在一起的家庭來說，情況遠不止於此。巴迪·卡西迪(Buddy Cassidy) 與杜興(Duchenne) 住在一起，也是一名Elevates 諮詢委員會成員，他分享了杜興(Duchenne) 社區對6 月批准的集體看法，其言辭比我所能表達的雄辯得多。正如我引用的巴迪所說：「還有更多的事情要做。但現在讓我們停下來，沐浴在我們成就的光輝之中。讓我們沐浴在感激之中。讓我們停下來慶祝。讓我們看著黎明昇起，帶來黎明。”天。”今年5月，FDA就我們的基因療法SRP-9001（現稱為ELEVIDYS）召開了諮詢委員會會議。諮詢委員會以多數票建議批准 ELEVIDYS 用於治療杜氏肌肉營養不良症門診患者。

On June 22, the FDA granted an accelerated approval for ELEVIDYS to treat Duchenne muscular dystrophy, currently labeled for 4- and 5-year-old patients. At the time of the approval, FDA leadership informed Sarepta and the patient community that if our confirmatory trial EMBARK meets its objectives, the FDA will, in the words of Dr. Peter Marks, move with a maximum speed following submission of the data to the agency, minimizing any impediments to review results rapidly and broadening the label by removing any age restrictions. So we have our path.

6 月 22 日，FDA 加速核准 ELEVIDYS 用於治療杜氏肌肉營養不良症，目前適用於 4 歲和 5 歲患者。在批准時，FDA 領導層告知 Sarepta 和患者社區，如果我們的驗證性試驗 EMBARK 達到其目標，用 Peter Marks 博士的話來說，FDA 將在向 FDA 提交數據後以最快的速度採取行動機構，最大限制地減少快速審查結果的障礙，並透過取消任何年齡限制來擴大標籤範圍。所以我們有我們的路。

Our confirmatory trial is well designed and powered to show a statistically significant benefit in the studied population. For the avoidance of doubt, we have powered this study to show a benefit in the studied population that's 4 to 7 years old. And with that, we will have confirmed the mechanism of action in Duchenne patients applicable to all age ranges. We will have the top line for EMBARK in the fourth quarter of this year. We will announce top line results as we submit them to the division, followed shortly by a label supplement.

我們的驗證性試驗經過精心設計，能夠在研究族群中顯示出統計上顯著的益處。為避免疑義，我們對這項研究進行了論證，以證明研究對 4 至 7 歲的研究族群有好處。至此，我們將確認適用於所有年齡層的 Duchenne 患者的作用機制。我們將在今年第四季獲得 EMBARK 的頂線。當我們將結果提交給該部門時，我們將公佈頂線結果，隨後不久將發布標籤補充。

If successful, we should be able to expand our label in the first half of 2024 to include the majority of Duchenne patients.

如果成功，我們應該能夠在 2024 年上半年擴大我們的標籤範圍，以涵蓋大多數 Duchenne 患者。

Additionally, we have already commenced our nonambulatory trial ENVISION or Study 303. And we intend to commence 2 trials with alternative approaches to cleaving or clearing preexisting antibodies. Our goal is to expand our label for ELEVIDYS to cover as much as 95% of the Duchenne patients.

此外，我們已經開始非動態試驗 ENVISION 或研究 303。我們打算開始兩項試驗，採用替代方法來裂解或清除預先存在的抗體。我們的目標是擴大 ELEVIDYS 的標籤覆蓋多達 95% 的 Duchenne 患者。

In a moment, our Chief Customer Officer, Dallan Murray, will provide details on the early days of the ELEVIDYS launch. ELEVIDYS is our fourth approved Duchenne therapy, and we have been very successful with all of our prior launches. Consistent with our track record, the ELEVIDYS launch is going well. A significant number of sites are now initiated and ready to infuse. Payer discussions and negotiations have been more positive than our prior successful therapies, and there is a significant amount of enthusiasm from physicians and families as we have a substantial number of start forms and more coming weekly.

稍後，我們的首席客戶長 Dallan Murray 將提供 ELEVIDYS 推出初期的詳細資訊。 ELEVIDYS 是我們第四種核准的 Duchenne 療法，我們之前推出的所有產品都非常成功。與我們的往績一致，ELEVIDYS 的發布進展順利。大量站點現已啟動並準備注入。與我們之前成功的治療相比，付款人討論和談判更加積極，而且醫生和家庭也表現出極大的熱情，因為我們有大量的開始表格，並且每週都會有更多表格。

In fact, I am pleased to announce that the first reimbursed ELEVIDYS infusion occurred earlier today. That is faster than we projected and speaks to the team's ability to execute. Now as positive as this is, please bear in mind that the significant ramp in infusions will begin later this year. This is primarily due to payer logistics and to the release protocol for ELEVIDYS, which requires that both we and the FDA release each lot. Shortly, our Head of Research and Development and Chief Scientific Officer, Dr. Louise Rodino-Klapac, will provide an overview of our development activities, including progress with our next-generation PPMO SRP-5051 and on the gene therapy side with our LGMD portfolio. To remind you, in addition to ELEVIDYS, we have a deep pipeline and are advancing a number of therapies in 2023. In fact, we have 24 ongoing human clinical trials by the end of this year. And we continue to advance our next-generation viral capsid, Myo AAV, which in early animal models, looks to be as much as tenfold more tropic than current AAVs.

事實上，我很高興地宣布今天早些時候進行了首次報銷的 ELEVIDYS 輸注。這比我們預期的要快，這說明了團隊的執行能力。儘管這是積極的，但請記住，輸注量的大幅增加將於今年稍後開始。這主要是由於付款人物流和 ELEVIDYS 的放行協議，該協議要求我們和 FDA 放行每批產品。很快，我們的研發主管兼首席科學官 Louise Rodino-Klapac 博士將概述我們的開發活動，包括我們下一代 PPMO SRP-5051 的進展以及我們 LGMD 產品組合在基因治療方面的進展。需要提醒您的是，除了 ELEVIDYS 之外，我們還有很深的產品線，並將在 2023 年推進多種療法。事實上，到今年年底，我們有 24 項正在進行的人體臨床試驗。我們繼續開發下一代病毒衣殼 Myo AAV，在早期動物模型中，它的熱帶性看起來比目前 AAV 強十倍。

From a manufacturing perspective, our technical operations professionals, more than 400 in all, are focused with our partner, Catalent, on producing and releasing lots to support our launch. Looking to the midterm, we will also continue to work to establish comparability at our Thermo Fisher plant for ELEVIDYS. And then looking to the future, we are advancing our approach to manufacturing to support our entire pipeline. In fact, we have made great progress in next-generation suspension technology, which we will use across our gene therapy portfolio, including the LGMD programs and even potentially for ELEVIDYS. In fact, we have largely completed our suspension-based process development for ELEVIDYS, and we have made three runs at 250 liters with a fourth run to occur later this year with the goal of scaling to 1,000 liters in the near term.

從製造角度來看，我們的技術營運專業人員總共有 400 多名，他們與我們的合作夥伴 Catalent 一起專注於生產和發布批次以支援我們的發布。展望中期，我們也將繼續努力在 Thermo Fisher 工廠為 ELEVIDYS 建立可比性。展望未來，我們正在推進我們的製造方法，以支持我們的整個管道。事實上，我們在下一代懸浮技術方面取得了巨大進展，我們將在我們的基因療法產品組合中使用該技術，包括 LGMD 項目，甚至可能用於 ELEVIDYS。事實上，我們已經基本完成了 ELEVIDYS 基於懸浮液的製程開發，並且我們已經進行了 3 次 250 公升的運行，第四次運行將於今年晚些時候進行，目標是在短期內擴展到 1,000 公升。

We have seen yields that are multiples greater than the current standard. As the leader in gene therapy for rare diseases, we will continue to focus on improving the science and the delivery of our therapies.

我們已經看到產量比目前標準高出數倍。作為罕見疾病基因治療領域的領導者，我們將繼續致力於改善科學和治療的實施。

Moving finally to quarterly performance. We have had another strong quarter with our 3 approved PMOs: EXONDYS, AMONDYS and VYONDYS. I am pleased to announce that second quarter total revenue came in at $261.2 million and net product revenue from our PMOs came in at $239 million, exceeding internal estimates and analyst consensus. In the second quarter, we saw no negative impact on the approved PMOs from any warehousing related to the ELEVIDYS approval and do not anticipate substantial impact over the course of the year. We remain comfortable with our full year guidance of $925 million for total PMO net product revenue, with a current bias to modestly exceeding that guidance. It is too early in the launch to provide an accurate guidance for ELEVIDYS, but we will continue to evaluate that.

最後轉向季度業績。我們的 3 個經批准的 PMO：EXONDYS、AMONDYS 和 VYONDYS 又迎來了一個強勁的季度。我很高興地宣布，第二季總營收為 2.612 億美元，我們 PMO 的產品淨收入為 2.39 億美元，超出了內部估計和分析師共識。在第二季度，我們沒有發現與 ELEVIDYS 批准相關的任何倉儲對已批准的 PMO 產生負面影響，並且預計全年不會產生重大影響。我們對全年 PMO 產品淨收入總額 9.25 億美元的指引感到滿意，目前傾向於略微超過該指引。現在為 ELEVIDYS 提供準確的指導還為時過早，但我們將繼續對此進行評估。

At Sarepta, we have a distinct culture. It is easy to say one is patient focus, but our words are backed by action. We put the welfare of our patients above all other considerations. And when necessary, we fight for them. And the tools we use for that fight include our commitment to scientific excellence and the courage to represent the patients who depend upon us. Our fight may not always be easy, but it is paying off. We have 4 approved therapies and a wealth of potentially life-enhancing programs in our pipeline. We will achieve $925 million on the first 3 of our 4 approved therapies this year. and far more next year when our newest approval is considered. We have a near-term high probability of success plan to broaden the label of the first and only gene therapy for Duchenne. And if our plans are successful, we could be profitable in the next few quarters. We have done a lot already, but with our plans, our pipeline and our commitment to dogged execution, we have only just begun. And with that, I will turn the call over to Dr. Rodino-Klapac, who will provide an update on our research and development progress. Louise?

在 Sarepta，我們擁有獨特的文化。說起來耐心專注很容易，但我們的言論是有行動支持的。我們將患者的福祉置於所有其他考慮因素之上。必要時，我們會為他們而戰。我們用於這場鬥爭的工具包括我們對卓越科學的承諾以及代表依賴我們的患者的勇氣。我們的鬥爭可能並不總是那麼容易，但它正在得到回報。我們有 4 種已獲批准的療法和大量潛在的改善生命的計畫正在醞釀中。今年我們將在 4 種獲批療法中的前 3 種上實現 9.25 億美元的收入。明年當我們考慮最新的批准時，還會有更多。我們有一個近期成功機率很高的計劃，以擴大第一個也是唯一一個杜氏基因療法的標籤。如果我們的計劃成功，我們可能會在未來幾季實現盈利。我們已經做了很多事情，但就我們的計劃、我們的管道以及我們對頑強執行的承諾而言，我們才剛剛開始。接下來，我會將電話轉給 Rodino-Klapac 博士，他將提供我們研發進展的最新資訊。路易絲？

Thanks, Doug. The accomplishments within R&D over the last quarter are many and highlighted by the approval of ELEVIDYS on June 22, 2023. The approval of ELEVIDYS via the accelerated approval pathway represents a win for the Duchenne community and an important step towards the broad approvals for individuals living with Duchenne, regardless of age or ambulatory status. As we look forward to the weeks and months ahead, we remain firmly committed to our values to follow the science and present objective evidence that supports ELEVIDYS ability to change the trajectory of Duchenne muscular dystrophy. Since 2018 and across multiple studies, we've dosed the largest number of Duchenne patients, more than any other gene therapy in development for this disease.

謝謝，道格。上一季研發方面取得的成就有很多，其中ELEVIDYS 於2023 年6 月22 日獲得批准凸顯了這一點。ELEVIDYS 透過加速批准途徑獲得批准代表了Duchenne 社區的勝利，也是邁向個人生活廣泛批准的重要一步。與杜興，無論年齡或行走狀態如何。展望未來幾週和幾個月，我們仍然堅定地致力於遵循科學的價值觀，並提供客觀證據，支持 ELEVIDYS 改變杜氏肌肉營養不良症發展軌蹟的能力。自 2018 年以來，在多項研究中，我們對 Duchenne 患者進行了最多的給藥，比針對這種疾病正在開發的任何其他基因療法都要多。

To remind you, we've shown consistent results across 3 clinical studies with respect to both biomarker expression and functional results. In clinical trials, ELEVIDYS demonstrated positive results at multiple time points, including 1, 2 and 4 years after treatment, in addition to a consistent safety profile. The BLA for ELEVIDYS included efficacy and safety data from studies 101, 102 and 103 or Endeavor as well as an integrated analysis across these 3 clinical studies, comparing functional results to propensity score matched external control.

提醒您，我們在 3 項臨床研究中在生物標記表達和功能結果方面顯示了一致的結果。在臨床試驗中，ELEVIDYS 在多個時間點（包括治療後 1 年、2 年和 4 年）顯示出正面的結果，此外還具有一致的安全性。 ELEVIDYS 的 BLA 包括來自研究 101、102 和 103 或 Endeavor 的功效和安全性數據，以及這 3 項臨床研究的綜合分析，將功能結果與傾向評分匹配的外部對照組進行比較。

Importantly, the functional data reinforced the consistency of NSAA improvement across these 3 independent trials and show mean improvements across key secondary functional endpoints such as time derived and 10-meter walk/run. The data from studies 101, 102 and 103 cohort 1, which is ages 4 to 7, have now been either published or accepted for publication in peer-reviewed journals. When compared to appropriate control populations, ELEVIDYS has consistently shown a treatment effect as measured by change in NSAA score at 1 year. We applied the learnings from studies 101, 102 and 103 in the design, the execution and statistical analysis plan for our Phase III EMBARK study.

重要的是，功能數據強化了這 3 項獨立試驗中 NSAA 改善的一致性，並顯示了關鍵次要功能終點（例如時間導出和 10 公尺步行/跑步）的平均改善。研究 101、102 和 103 第 1 組（年齡為 4 至 7 歲）的資料現已在同行評審期刊上發表或接受發表。與適當的對照組相比，ELEVIDYS 始終顯示出治療效果（以 1 年 NSAA 評分的變化來衡量）。我們將研究 101、102 和 103 的經驗教訓應用於 III 期 EMBARK 研究的設計、執行和統計分析計劃。

To remind you, EMBARK is a double-blind, randomized, placebo-controlled trial of ELEVIDYS in Duchenne patients ages 4 to 7. We completed enrollment in the fall of 2022. The trial will be considered successful if the entire treated population shows a statistically significant positive difference in NSAA scores at 1 year compared to placebo. Our conviction around EMBARK is founded in data and was designed based on our experience with studies 101, 102 and 103, along with our propensity-weighted external controls and natural history data sources. We took extensive measures to ensure success, which includes the following.

提醒您，EMBARK 是一項針對ELEVIDYS 在4 至7 歲Duchenne 患者中進行的雙盲、隨機、安慰劑對照試驗。我們於2022 年秋季完成入組。如果整個治療人群顯示出統計數據，則該試驗將被視為成功。與安慰劑相比，1 年時 NSAA 評分有顯著正向差異。我們對 EMBARK 的信念建立在資料之上，並且是根據我們在研究 101、102 和 103 中的經驗以及我們的傾向加權外部控制和自然歷史資料來源而設計的。我們採取了廣泛的措施來確保成功，其中包括以下措施。

The EMBARK study design improves on Study 102 with measures to increase homogeneity, including a floor and a ceiling on baseline NSAA and a requirement for rise in floors to be less than 5 seconds of screening. We also ensured a balanced distribution between treatment arms by including a stratification factor for baseline NSAA score. We also increased the target sample size to 120 to increase power and enrolled 125 patients. All of these measures results in a study powered well over 90%.

EMBARK 研究設計在研究 102 的基礎上進行了改進，採取了提高同質性的措施，包括 NSAA 基線的下限和上限，以及要求下限上升的時間不得超過篩選 5 秒。我們也透過納入基線 NSAA 評分的分層因子來確保治療組之間的平衡分佈。我們還將目標樣本量增加到 120 個以提高功效，並招募了 125 名患者。所有這些措施的結果是研究的有效率遠超過 90%。

As discussed at the Advisory Committee in May, we assumed standard deviation of 3.5 points in 120 patients. EMBARK was powered greater than 90% to see a 2.2 points difference on NSAA. Thus, we've always been confident in the powering of the study. We've also done extensive analysis and modeling that provides additional confidence in the success of EMBARK.

如同 5 月諮詢委員會所討論的，我們假設 120 名患者的標準差為 3.5 分。 EMBARK 的動力超過 90%，與 NSAA 相比有 2.2 分的差異。因此，我們一直對這項研究的動力充滿信心。我們也進行了廣泛的分析和建模，為 EMBARK 的成功提供了更多信心。

First, when we integrated summary of efficacy population included in the BLA, which was an Exon 52, is narrowed to those who meet 301 entry criteria for an Exon 33, the standard deviation goes down, confirming increased homogeneity. We also performed simulation models of 4 scenarios drawn from existing program data that have all yielded greater than 90% power.

首先，當我們整合 BLA 中包含的功效群體（外顯子 52）的匯總，縮小到滿足外顯子 33 的 301 條進入標準的人群時，標準差下降，證實同質性增加。我們還對從現有程式資料中提取的 4 個場景進行了模擬模型，這些場景的功率均超過 90%。

Given the entire protocol, we're able to detect an even lower treatment effect. For example, with an assumed standard deviation of 3.5 points, our analysis will predict statistical significance at observed treatment effects in the overall intent-to-treat population as low as 1.3 points. Taken together, we have strong confidence in the Part 1 readout of EMBARK.

考慮到整個方案，我們能夠檢測到甚至更低的治療效果。例如，假設標準差為 3.5 分，我們的分析將預測總體意圖治療族群中觀察到的治療效果的統計顯著性低至 1.3 分。總而言之，我們對 EMBARK 第 1 部分的讀數充滿信心。

With regards to additional ELEVIDYS studies, we've commenced dosing ENVISION, a placebo controlled Phase III study in nonambulant and older ambulant patients with Duchenne. We are also on track to convince an apheresis study as well as an imlifidase study in AAV-Rh74 antibody-positive Duchenne patients this year. This is all with the goal of serving the entire Duchenne population.

關於其他 ELEVIDYS 研究，我們已經開始對 ENVISION 進行給藥，這是一項針對非行走性和老年行走性 Duchenne 患者的安慰劑對照 III 期研究。今年我們還有望說服 AAV-Rh74 抗體陽性 Duchenne 患者進行單採研究和酰亞胺酶研究。這一切都是為了服務整個杜興人口。

Now moving to limb-girdle muscular dystrophy or LGMD. We remain committed to advancing our LGMD portfolio across a variety of subtypes and look forward to providing updates on these important programs in the months ahead. We're pleased to report that we have fully enrolled Journey, our LGMD natural history study. 126 patients with Sarcoglycanopathy have been enrolled and will be followed for 36 months. We've also made excellent progress enrolling VOYAGENE, our Phase I study evaluating SRP-9003 for the treatment of limb-girdle muscular dystrophy type 2E in ambulant adult patients and nonambulant patients using clinical process SRP-9003 material.

現在轉向肢帶型肌肉營養不良症（LGMD）。我們仍然致力於在各種亞型中推進我們的 LGMD 產品組合，並期待在未來幾個月提供這些重要項目的最新資訊。我們很高興地報告，我們已經完全註冊了「Journey」（我們的 LGMD 自然歷史研究）。 126 名肌聚醣症患者已入組，並將接受為期 36 個月的追蹤。我們在VOYAGENE 入組方面也取得了巨大進展，這是我們的I 期研究，該研究使用臨床過程SRP-9003 材料評估SRP-9003 對可行走的成人患者和不可行走的患者治療2E 型肢帶型肌肉營養不良症的效果。

Combined with positive expression and functional data shared from our initial study, SRP-9003, 101, we believe the data from VOYAGENE will give us insights into a broader patient population. Our next milestones for VOYAGENE include completing enrollment in Q3 of this year, and initiating our Phase III study using commercially representative process material later in the year.

結合我們最初研究 SRP-9003, 101 中分享的陽性表達和功能數據，我們相信 VOYAGENE 的數據將使我們深入了解更廣泛的患者群體。我們 VOYAGENE 的下一個里程碑包括在今年第三季完成註冊，並在今年稍後使用具有商業代表性的製程材料啟動我們的 III 期研究。

Finally, we've commenced dosing of a systemic pilot study, NAVIGENE, for our SRP 6004 dual vector rh74-mediated gene therapy to treat LGMD2B, characterized by the absence of the protein, dysferlin. The innovative dual vector strategy allows us to deliver the full length of ferlin gene, the sole cause of LGMD2B. We also continue to make progress in manufacturing for all LGMD candidates in our pipeline and look forward to initiating clinical studies as rapidly as possible.

最後，我們已經開始對 SRP 6004 雙載體 rh74 介導的基因療法進行系統性試驗研究 NAVIGENE 的劑量，以治療 LGMD2B，其特徵是缺乏 Dysferlin 蛋白。創新的雙載體策略使我們能夠提供全長的 ferlin 基因，這是 LGMD2B 的唯一原因。我們也將繼續在我們管道中的所有 LGMD 候選藥物的生產方面取得進展，並期待盡快啟動臨床研究。

Turning now to the progress we've made with our RNA platform. We were pleased to complete enrollment in the first quarter of 2023 for MOMENTUM study for SRP 5051, and we remain on track to announce data from this study in the back half of 2023.

現在談談我們的 RNA 平台所取得的進展。我們很高興在 2023 年第一季完成 SRP 5051 MOMENTUM 研究的入組，並且我們仍有望在 2023 年下半年公佈這項研究的數據。

In regard to our post-marketing studies for the PMO, as mentioned last quarter, we completed enrollment in the ESSENCE trial, our post-marketing requirement for Golodirsen and casimersen, and continue to make good progress with our MIS51ON study, which is on track to be fully enrolled this year.

關於我們的PMO 上市後研究，正如上季度提到的，我們完成了ESSENCE 試驗的註冊，這是我們對Golodirsen 和casimersen 的上市後要求，並且我們的MIS51ON 研究繼續取得良好進展，該研究正在按計劃進行今年將全面招生。

The accomplishments of 2023 and the opportunities before us speak to the promise of science to fundamentally impact and change the lives of patients around the world. On the research side, we continue to make excellent progress on the Myo AAV platform, along with an exciting pipeline of genetic medicine candidates. My deepest gratitude to our R&D colleagues across RNA, gene therapy and gene editing for their extraordinary work to get us where we are today.

2023 年的成就和我們面前的機會證明了科學有望從根本上影響和改變世界各地患者的生活。在研究方面，我們繼續在 Myo AAV 平台以及令人興奮的基因醫學候選產品管線上取得出色進展。我對 RNA、基因治療和基因編輯領域的研發同事表示最深切的感謝，他們的出色工作使我們取得了今天的成就。

Finally, to the patient community, we understand the urgency and we're working tirelessly to bring forth transformative genetic medicines as rapidly as science will allow. We are doing everything we can to expedite the EMBARK study readout so that we can expand the ELEVIDYS label. We expect the data will be available in the next 3 to 4 months. I will now turn the call over to Dallan for an update on our commercial activities. Dallan?

最後，對於患者群體，我們理解緊迫性，我們正在不懈地努力，以科學允許的速度盡快推出變革性基因藥物。我們正在盡一切努力加快 EMBARK 研究結果，以便我們能夠擴大 ELEVIDYS 標籤的範圍。我們預計數據將在未來 3 至 4 個月內提供。我現在將把電話轉給達蘭，以了解我們商業活動的最新情況。達蘭？

Thank you, Louise, and good afternoon. We were thrilled to receive approval for ELEVIDYS on June 22, and we owe a tremendous debt of gratitude to the patients who participated in the trials, the KOLs and our R&D colleagues for getting us to this point. As Doug and Louise have said, we are deeply committed to broadening the label at the earliest time point that is feasible. During this time, the team is diligently working day and night to expedite access to this potentially transformative therapy for all eligible 4- to 5-year-old Duchenne patients.

謝謝你，路易絲，下午好。我們很高興 ELEVIDYS 在 6 月 22 日獲得批准，我們非常感謝參與試驗的患者、KOL 和我們的研發同事，是他們讓我們走到了這一步。正如道格和路易絲所說，我們堅定地致力於在可行的最早時間點擴大品牌範圍。在此期間，團隊日以繼夜地努力工作，以加快所有符合條件的 4 至 5 歲 Duchenne 患者獲得這種潛在的變革性療法。

Their dedication is focused on ensuring swift and seamless access for those who can benefit from ELEVIDYS. In these early stages, much of our focus is on supporting those sites who have boys turning 6 years old. At the same time, we are also rapidly preparing the sites to treat all of the patients who are eligible today and laying the groundwork to be ready for a broader patient population when the time comes. The team's remarkable progress and unwavering sense of urgency in executing our now 4 Duchenne launches are truly commendable and reflect our commitment to providing timely access to potentially transformative therapies for patients. The commercial and medical teams began educating the centers within 24 hours of approval, as we've done in our previous 3 launches. Right from day 1, our case managers were fully prepared to assist patients in navigating the intricate aspects of the gene therapy treatment journey.

他們致力於確保那些能夠從 ELEVIDYS 中受益的人能夠快速、無縫地存取。在早期階段，我們的重點是支持那些有 6 歲以上男孩的網站。同時，我們也正在迅速準備場地來治療今天符合條件的所有患者，並為當時機成熟時為更廣泛的患者群體做好準備奠定基礎。該團隊在執行我們目前的 4 項 Duchenne 上市過程中所取得的顯著進展和堅定不移的緊迫感確實值得稱讚，並反映了我們致力於為患者及時提供潛在變革性療法的承諾。正如我們在前 3 次啟動中所做的那樣，商業和醫療團隊在獲得批准後 24 小時內開始對中心進行教育。從第一天起，我們的個案經理就做好了充分準備，協助患者應對基因治療旅程中的複雜問題。

Doug has previously highlighted the unique components of a gene therapy launch, which we must get right in order to serve the community. The 3 areas of focus are site readiness, payer engagement, and building the capabilities for antibody testing.

道格先前曾強調基因療法推出的獨特組成部分，我們必須正確對待這些組成部分才能為社區服務。三個重點領域是現場準備、付款人參與以及抗體測試能力建構。

In terms of gene therapy site readiness, as of today, we have over 50 sites trained, activated and ready to receive product. We have achieved this ahead of our own aggressive timelines.

在基因治療站點準備方面，截至目前，我們已有 50 多個站點經過培訓、啟動並準備好接收產品。我們已經提前實現了這個目標。

On the payer front, since approval, the team has engaged both commercial and Medicaid payers, representing approximately 250 million lives. Continued progress has been made in educating and informing them on the clinical data to support policy formation to our approved FDA label.

在付款人方面，自批准以來，該團隊已與商業和醫療補助付款人合作，代表了約 2.5 億人的生命。在對他們進行臨床數據教育和宣傳方面取得了持續進展，以支持針對我們批准的 FDA 標籤制定政策。

As an example, United Healthcare, one of the largest commercial insurers in the United States, published their coverage policy for ELEVIDYS yesterday, aligning the therapy to its FDA-approved label.

例如，美國最大的商業保險公司之一 United Healthcare 昨天發布了 ELEVIDYS 的承保政策，使該療法與其 FDA 批准的標籤保持一致。

And finally, to touch on antibody testing. Over 700 kits were in the hands of our key sites within a day or 2 of approval. Testing is currently underway and the process is working smoothly. We've seen very strong demand for ELEVIDYS and are encouraged by the discussions with KOLs, payers and the broader community. We began receiving enrollment forms within hours of approval and we continue to see them come in on a daily basis.

最後，談談抗體檢測。在批准後一兩天內，我們的主要站點就收到了 700 多個套件。目前測試正在進行中，過程進展順利。我們看到對 ELEVIDYS 的需求非常強勁，並受到與 KOL、付款人和更廣泛社區的討論的鼓舞。我們在批准後的幾小時內就開始收到註冊表格，並且每天都會看到這些表格。

Since June 22, the team has had over 500 interactions with both treating and referring sites. In these early discussions, our focus has been, first and foremost, on patient safety, eligibility, procurement, dosing and preparation and reimbursement. Launching the first gene therapy for Duchenne patients requires a multifaceted approach with a high level of communication, not only with HCPs and sites but also patients, families and payers to ensure patients have timely access to this groundbreaking therapy.

自 6 月 22 日以來，該團隊已與治療和轉診站點進行了 500 多次互動。在這些早期討論中，我們的重點首先是病人安全、資格、採購、劑量、準備和報銷。為 Duchenne 患者推出首個基因療法需要採取多方面的方法和高水平的溝通，不僅與 HCP 和場所，而且與患者、家屬和付款人進行溝通，以確保患者能夠及時獲得這種突破性的治療。

As a result of our preparation and diligent efforts, we are now at the point where patients can begin receiving ELEVIDYS with confidence. As I previously highlighted, our engagement with payers has been constructive. The team is optimistic in making progress towards our goal of ensuring timely access. Of note, we are seeing states reach out to their local KOLs and experts to inform policies. We expect to have payer policies in place within 3 to 6 months depending on the plan.

經過我們的準備和不懈努力，我們現在已經到了患者可以充滿信心地開始接受 ELEVIDYS 治療的階段。正如我之前所強調的，我們與付款人的接觸是建設性的。該團隊對於在確保及時訪問的目標方面取得進展持樂觀態度。值得注意的是，我們看到各州向當地的 KOL 和專家伸出援手，為政策提供資訊。我們預計將根據計劃在 3 至 6 個月內制定付款政策。

In the interim, we are working with payers on a case-by-case basis to obtain access for patients. To that end, we have received multiple authorizations. And as Doug mentioned, we were thrilled to announce that the first patient was dosed today. Over the course of the next 1.5 weeks, we have a handful of additional infusions across the country scheduled with patients representing a combination of commercial and Medicaid insurance coverage.

在此期間，我們正在根據具體情況與付款人合作，為患者提供使用機會。為此，我們已獲得多項授權。正如道格所提到的，我們很高興地宣布今天第一位患者接受了給藥。在接下來的 1.5 週內，我們計劃在全國範圍內對代表商業和醫療補助保險範圍的患者進行幾次額外的輸注。

We are gratified by the tremendous work being done across the country to support patients. In particular, there has been a concerted effort since approval to rally around those patients who are approaching their sixth birthday. The incredible efforts to support those patients from all involved has been truly humbling. While we are encouraged by our progress and accomplishments to date, it's important to reiterate that we are not providing revenue guidance in the early stages of this one-of-a-kind launch. As Doug made clear on the approval call, we expect this to take some time in the early stages before dosing can begin in earnest to generate the launch ramp we are confident will come.

我們對全國各地為支持患者所做的大量工作感到滿意。特別是，自從批准以來，人們一直在共同努力，團結在那些即將六歲生日的患者周圍。所有相關人員為支持這些患者所做的令人難以置信的努力確實令人感到謙卑。雖然我們對迄今為止的進展和成就感到鼓舞，但重要的是要重申，我們不會在這一獨一無二的發布的早期階段提供收入指導。正如道格在批准呼籲中明確表示的那樣，我們預計在早期階段需要一些時間才能認真開始劑量，以產生我們有信心實現的發射斜坡。

I want to take a moment prior to reflecting on our PMO business to thank everyone within Sarepta and our key partners who have worked so hard to make this launch a reality and allowed us to be ready to serve these patients right from day 1.

在回顧我們的PMO 業務之前，我想花一點時間感謝Sarepta 內部的每個人以及我們的主要合作夥伴，他們為使此次發布成為現實而付出了巨大的努力，並使我們能夠從第一天起就做好為這些患者提供服務的準備。

Now regarding our PMO business, it's critical to highlight the fact that we have not lost a step supporting our PMO patient community, while we've risen to the challenge of the first Duchenne gene therapy launch. As Doug mentioned, we delivered $239 million in net product revenue in the second quarter, representing 13.1% growth over the second quarter of 2022. EXONDYS 51 totaled $134.7 million, representing 6.6% growth over Q2 of '22. For VYONDYS 53, sales were $32.6 million, growing roughly 8.2% over the second quarter of 2022. And for AMONDYS 45, sales totaled $71.7 million, representing more than 31% growth versus Q2 of 2022.

現在，關於我們的 PMO 業務，重要的是要強調這樣一個事實：我們在支持 PMO 患者社群的同時，也沒有放棄支持 PMO 患者社群的一步，同時我們已經迎接了第一個 Duchenne 基因療法推出的挑戰。正如 Doug 所提到的，我們第二季度實現了 2.39 億美元的產品淨收入，比 2022 年第二季度增長 13.1%。EXONDYS 51 總計 1.347 億美元，比 22 年第二季度增長 6.6%。 VYONDYS 53 的銷售額為 3,260 萬美元，比 2022 年第二季成長約 8.2%。AMONDYS 45 的銷售額總計 7,170 萬美元，比 2022 年第二季成長超過 31%。

Total ex U.S. net product revenue in the second quarter was roughly $35 million. This represented an increase over the prior quarter, which was expected and fully reflected in our annual guidance and forecast. As discussed on last quarter's call, we expect to see even more quarter-to-quarter fluctuations in the overall net product revenue as the ex U.S. becomes a bigger percentage of the overall PMO mix. Importantly, these quarter-to-quarter fluctuations along with the shifting mix of the PMO revenue base have all been anticipated and fully reflected in our annual guidance.

第二季除美國外的產品淨收入總額約 3,500 萬美元。這比上一季度有所增長，這是我們的預期並充分反映在我們的年度指導和預測中。正如上季度電話會議中所討論的那樣，隨著美國以外的地區在 PMO 總體組合中所佔的比例越來越大，我們預計整體淨產品收入的季度波動會更大。重要的是，這些季度間的波動以及 PMO 收入基礎的變化都已在我們的年度指引中預期並充分反映。

Overall, the fundamentals of the PMO business coming out of Q2 are completely in line with what we expected at this point in the year and we reiterate our full year guidance of $925 million in net product revenue for our PMO therapies.

總體而言，第二季 PMO 業務的基本面完全符合我們今年此時的預期，我們重申 PMO 療法的全年產品淨收入為 9.25 億美元的指導。

In closing, our teams are fully engaged and executing today to support patients with all 4 of our approved therapies. I'm particularly pleased to see the continued success of our PMO business in the second quarter. In fact, looking back on the execution of all 3 of our PMO launches should provide a high level of confidence in the future of Sarepta and our potential to transform the Duchenne space with ELEVIDYS and pave the way for precision genetic medicines for other rare patient populations such as limb-girdle muscular dystrophy. And with that, I'll turn the call over to Ian Estepan for an update on our financials. Ian?

最後，我們的團隊今天全力投入並執行，以支持患者使用我們批准的所有 4 種療法。我特別高興地看到我們的 PMO 業務在第二季度持續取得成功。事實上，回顧我們所有 3 個 PMO 發布的執行情況，應該讓我們對 Sarepta 的未來以及我們透過 ELEVIDYS 改變 Duchenne 領域的潛力充滿信心，並為其他罕見患者群體的精準基因藥物鋪平道路例如肢帶型肌肉營養不良症。接下來，我會將電話轉給伊恩‧埃斯特潘 (Ian Estepan)，以了解我們財務狀況的最新情況。伊恩？

Thanks, Dallan, and good afternoon, everyone. This afternoon's financial results press release provided details for the second quarter of 2023 on a non-GAAP basis as well as a GAAP basis. Please refer to the press release available on Sarepta's website for a full reconciliation of GAAP to non-GAAP financial results.

謝謝達蘭，大家下午好。今天下午的財務業績新聞稿提供了按非公認會計原則和公認會計原則計算的 2023 年第二季度的詳細資訊。請參閱 Sarepta 網站上的新聞稿，以了解 GAAP 與非 GAAP 財務表現的全面對帳。

For the 3 months ended June 30, 2023, the company recorded total revenues of $261.2 million, which consists of net product revenues and collaboration revenues compared to revenues of $233.5 million for the same period of 2022, an increase of $27.7 million. Net product revenue for the second quarter of 2023 from our PMO exon skipping franchise was $239 million compared to $211.2 million for the same period of 2022. The increase in net product revenue primarily reflects increasing demand for our PMO products.

截至2023年6月30日的三個月，該公司的總收入為2.612億美元，其中包括淨產品收入和協作收入，與2022年同期的收入2.335億美元相比，增加了2,770萬美元。 2023 年第二季度，我們的PMO 外顯子跳躍特許經營權的產品淨收入為2.39 億美元，而2022 年同期為2.112 億美元。產品淨收入的增長主要反映了對我們PMO 產品的需求不斷增長。

In each of the quarters ended June 30, 2023 and 2022, we recognized $22.3 million of collaboration revenues, which relates to our collaboration arrangement with Roche. The reimbursable co-development costs under the Roche agreement totaled $28.2 million for the second quarter of 2023 compared to $26.4 million for the same period of 2022. On a GAAP basis, we reported a net loss of $23.9 million or $0.27 per basic and diluted share and $231.5 million or $2.65 per basic and diluted share for the second quarter of 2023 and 2022, respectively. We reported a non-GAAP net loss of $75.2 million or $0.85 per basic and diluted share in the second quarter of 2023 compared to a non-GAAP net loss of $103 million or $1.18 per basic and diluted share in the second quarter of 2022.

在截至 2023 年 6 月 30 日和 2022 年 6 月 30 日的每個季度中，我們確認了 2,230 萬美元的合作收入，這與我們與羅氏的合作安排有關。 2023 年第二季度，羅氏協議下的可報銷共同開發費用總計2,820 萬美元，而2022 年同期為2,640 萬美元。根據GAAP 計算，我們報告淨虧損2,390 萬美元，即每股基本股和稀釋股虧損0.27 美元2023 年第二季和 2022 年第二季分別為 2.315 億美元或每股基本股和稀釋股 2.65 美元。我們報告2023 年第二季的非GAAP 淨虧損為7,520 萬美元，即每股基本股和稀釋股0.85 美元，而2022 年第二季的非GAAP 淨虧損為1.03 億美元，即每股基本股和稀釋股1.18 美元。

In the second quarter of 2023, we recorded approximately $34.1 million in cost of sales compared to $37.8 million in the same period of 2022. The decrease in cost of sales primarily reflects a decrease in our royalty payments during the 3 months ended June 30, 2023, due to changes in the BioMarin royalty terms and a decrease in write-offs of certain batches of our products not meeting our quality specifications for the 3 months ended June 30, 2023, as compared to the same period of 2022, partially offset by an increase in demand for our PMO products.

2023年第二季度，我們的銷售成本約為3,410萬美元，而2022年同期為3,780萬美元。銷售成本的下降主要反映了截至2023年6月30日的三個月內我們的特許權使用費的減少，由於 BioMarin 特許權使用費條款發生變化，以及截至 2023 年 6 月 30 日止 3 個月，與 2022 年同期相比，不符合我們品質規格的某些批次產品的沖銷減少，部分被對我們PMO 產品的需求增加。

On a GAAP basis, we recorded $241.9 million and $252.3 million in R&D expenses for the second quarter of 2023 and 2022, respectively, a year-over-year decrease of $10.4 million. The decrease is primarily due to a decrease in manufacturing expenses partially offset by increase in clinical trial expenses and compensation and other personnel expenses.

以公認會計原則計算，2023 年第二季和 2022 年第二季的研發費用分別為 2.419 億美元和 2.523 億美元，年比減少 1,040 萬美元。減少的主要原因是製造費用的減少被臨床試驗費用以及薪酬和其他人員費用的增加部分抵消。

On a non-GAAP basis, R&D expenses were $212.2 million for the second quarter of 2023 compared to $230.4 million for the same period of 2022, a decrease of $18.2 million.

以非公認會計原則計算，2023年第二季的研發費用為2.122億美元，與2022年同期的2.304億美元相比，減少了1,820萬美元。

Now turning to SG&A. On a GAAP basis, we recorded approximately $118.6 million and $154.3 million of expenses for the second quarters of 2023 and 2022, respectively, a decrease of $35.7 million. The decrease was driven primarily by a decrease in stock-based compensation expense. On a non-GAAP basis, SG&A expenses were $90.3 million for the second quarter of 2023 compared to $63.7 million for the same period of 2022, an increase of $26.6 million.

現在轉向SG&A。根據公認會計原則，我們在 2023 年和 2022 年第二季的支出分別約為 1.186 億美元和 1.543 億美元，減少了 3,570 萬美元。這一下降主要是由於股票薪酬費用的減少所致。以非公認會計準則計算，2023 年第二季的銷售、管理及行政費用為 9,030 萬美元，而 2022 年同期為 6,370 萬美元，增加了 2,660 萬美元。

On a GAAP basis, we recorded $16.9 million in other income net for the second quarter of 2023 compared to $17 million in other expense net for the same period of 2022. The change is primarily due to an increase in interest income and accretion of investment discount due to the investment mix of our investment portfolio as well as a reduction of interest expense incurred as a result of the repayment of our December 2019 term loan during 2022.

根據公認會計原則，我們 2023 年第二季的其他收入淨額為 1,690 萬美元，而 2022 年同期的其他支出淨額為 1,700 萬美元。這項變更主要是由於利息收入的增加和投資折扣的增加由於我們的投資組合的投資組合以及由於我們在2022 年償還2019 年12 月定期貸款而產生的利息費用減少。

In the second quarter, we entered into an agreement to sell the rare pediatric disease Priority Review Voucher received from the FDA in connection with the approval of ELEVIDYS for a consideration of $102 million with no commission cost. The net proceeds were recorded as a gain from the sale of the PRV as ELEVIDYS did not have a carrying value at the time of the sale.

第二季度，我們簽訂了一項協議，出售從 FDA 收到的與 ELEVIDYS 批准有關的罕見兒科疾病優先審查券，價格為 1.02 億美元，無需支付佣金。由於 ELEVIDYS 在出售時沒有帳面價值，因此淨收益記錄為出售 PRV 的收益。

And finally, we had approximately $1.9 billion in cash, cash equivalents, investments and long-term restricted cash as of June 30, 2023. So in closing, I'd just like to reiterate how exciting time it is for Sarepta and the patients we serve, seeing the first patient dosed today, brought true joy to all of our hearts.

最後，截至2023 年6 月30 日，我們擁有約19 億美元的現金、現金等價物、投資和長期限制性現金。因此，最後，我想重申，對於Sarepta 和我們的患者來說，這是多麼激動人心的時刻今天看到第一位病人服藥，給我們所有人帶來了真正的喜悅。

And then from a financial perspective, we're looking forward to being one of the rare biotech companies to actually make the transition to profitability. In fact, we anticipate becoming non-GAAP EPS positive in the upcoming quarters. So this has truly been quite an accomplishment on all fronts for us and we're particularly proud of what we've been able to do. And with that, I'll turn the call over back to Doug to start the Q&A.

然後從財務角度來看，我們期待成為少數真正實現獲利轉型的生技公司之一。事實上，我們預期未來幾季的非公認會計準則每股盈餘將變為正數。因此，這對我們來說在各個方面確實是一項相當大的成就，我們對我們能夠做到的事情感到特別自豪。然後，我會將電話轉回給道格開始問答。

Thank you very much, Ian, and hear, hear to those last comments.

非常感謝你，伊恩，聽聽最後的評論。

Jonathan, let's open the call for questions.

喬納森，讓我們開始提問。

(Operator Instructions) Our first question comes from the line of Colin Bristow from UBS.

（操作員說明）我們的第一個問題來自 UBS 的 Colin Bristow。

Congrats on another mark then with the first patient dosed. I guess a sort of 2-part question around the comments you made around EMBARK. Hitting with as low as a 1.3 point delta. I'm curious, what is the powering the 1.3 delta is at? And has there been any discussion with FDA whether this would be considered clinically meaningful? And then just as a sort of follow-up on that, I think the most common question we're getting is that if EMBARK misses the primary and the overall population that shows a directional benefit in 4- to 5-year-olds, given there's no multiplicity strategy, has the FDA given any indication on whether this would be sufficient to maintain the approval status?

恭喜第一位患者服藥後又取得了另一個成績。我想這是一個由兩部分組成的問題，圍繞著您對 EMBARK 所做的評論。擊球差值低至 1.3 點。我很好奇，1.3 delta 的功率是多少？是否與 FDA 討論過這是否具有臨床意義？然後，作為對此的一種後續行動，我認為我們遇到的最常見的問題是，如果 EMBARK 錯過了初選和總體人群，那麼這會在 4 至 5 歲兒童中顯示出定向益處，因為沒有多重策略，FDA 是否顯示這是否足以維持核准狀態？

So I'm going to turn the question over to Louise on the powering issue. But real quickly, just on the latter question. So we haven't had discussions with the agency directly about clinically meaningfulness of a particular number. But I want to remind you that the effect one sees at 52 weeks isn't the effect. It's a signal of the long-term effect. Using an artful metaphor, if we took off in from Los Angeles, and we were 1 degree off trying to get to Tokyo, by the time we hit Catalina Island, we wouldn't be that far off. But if we continue with that 1 degree, we'd be 500, 600, 700 miles away from Tokyo. That's what we're dealing with here. This is a disease that is degenerative over time. If we can see a statistically significant benefit in a mere 52 weeks, we have clearly changed the trajectory of this disease in a very positive way. So with that said, let me turn the technical question on the powering calculations over to Dr. Rodino-Klapac.

因此，我將把有關供電問題的問題轉交給路易絲。但很快，就後一個問題。因此，我們尚未與該機構直接討論特定數字的臨床意義。但我想提醒你的是，52週時看到的效果並不是效果。這是長期影響的訊號。用一個巧妙的比喻來說，如果我們從洛杉磯起飛，距離東京只有 1 度，那麼當我們到達卡特琳娜島時，距離就不會那麼遠了。但如果我們繼續保持 1 度，我們將距離東京 500、600、700 英里。這就是我們正在處理的事情。這是一種隨著時間的推移而退化的疾病。如果我們能夠在短短 52 週內看到統計上顯著的益處，那麼我們顯然已經以非常積極的方式改變了這種疾病的發展軌跡。話雖如此，讓我將有關動力運算的技術問題轉交給 Rodino-Klapac 博士。

Thanks, Doug. So based on the modeling that we did, this isn't a traditional power calculation. So this was a simulation model in order to determine the lowest effect size that we could see in order to hit stat sig. So we put the following assumptions into our model, which was in 125 patients, which is the number of patients we enrolled. No dropouts because we've not seen any dropouts in EMBARK. We assumed a standard deviation of 3.5% across the entire 4- to 7-year-old population. And then we varied the effect size in order to see how low we could go in order to still hit statistical significance. And that's how we arrive at the equal to or greater than 1.3 as the lowest number. This isn't the assumed effect size. This is as low as the modeling will show us to still see statistical significance.

謝謝，道格。因此，根據我們所做的建模，這不是傳統的功率計算。所以這是一個模擬模型，目的是確定我們可以看到的達到 stat sig 的最低效應量。因此，我們將以下假設放入我們的模型中，該模型有 125 名患者，這就是我們招募的患者人數。沒有輟學，因為我們在 EMBARK 中沒有看到任何輟學。我們假設整個 4 至 7 歲族群的標準差為 3.5%。然後我們改變效應大小，看看我們可以降低到多低才能仍然達到統計顯著性。這就是我們如何得出等於或大於 1.3 的最低數字。這不是假設的效應大小。該模型將向我們展示仍然可以看到統計顯著性的最低值。

And then one final thing. Colin, you had asked about the way the agency would look at the data. Again, we are powered for success and EMBARK, and our goal is to see a statistically significant meaningful benefit from the therapy in 52 weeks. At the end of the day, the agency standard is to look at the totality of evidence across the primary and the secondary. So sort of statistical significance, we look at, presumably, we look at the totality of evidence to justify the mechanism of action and expand the label to the broader population.

最後一件事。科林，您曾詢問該機構如何看待數據。再次強調，我們有動力走向成功並出發，我們的目標是在 52 週內看到該療法在統計上顯著且有意義的益處。歸根結底，該機構的標準是查看主要和次要證據的整體性。因此，我們會研究統計顯著性，大概我們會研究全部證據來證明作用機制的合理性，並將標籤擴展到更廣泛的人群。

And our next question comes from the line of Brian Abrahams from RBC Capital Markets.

我們的下一個問題來自加拿大皇家銀行資本市場部門的布萊恩亞伯拉罕斯 (Brian Abrahams)。

So in the back half of this year, we're going to see data from several late-stage DMD gene therapies. I guess I'm curious, based on what you're seeing on the ground so far. If you have a sense as to what physicians and patients are going to be looking for as they potentially choose a gene therapy to take, assuming there's multiple therapies available. What are your views on the potential approval paths based on interim functional analysis? Is that something that you guys ever explored with or contemplated or explore with the FDA?

因此，今年下半年，我們將看到幾種後期 DMD 基因療法的數據。根據你目前所看到的情況，我想我很好奇。如果您知道醫生和患者在選擇基因療法時會尋求什麼，假設有多種療法可用。您對基於中期功能分析的潛在核准路徑有何看法？你們是否曾經與 FDA 一起探索、考慮或探索過這個問題？

We are not -- we have -- there's one therapy that's approved for Duchenne muscular dystrophy that's a gene therapy. And to be honest, we think very little about other organizations right now. We have a path in front of us. We have to serve the patients that are available to benefit from our therapy today, and we need to broaden that label. And that's what we're focused on right now. And of the things that we worry about right now, those are the -- all of the top priorities and worrying about other organizations and their plans is tertiary or less than tertiary to us.

我們沒有——我們有——有一種療法被批准用於杜氏肌肉營養不良症，那就是基因療法。老實說，我們現在很少考慮其他組織。我們面前有一條路。我們必須為那些能夠從我們今天的治療中受益的患者提供服務，並且我們需要擴大這個標籤。這就是我們現在關注的重點。在我們現在擔心的事情中，這些都是最重要的事情，而擔心其他組織及其計劃對我們來說是第三位或不那麼重要。

And our next question comes from the line of Tazeen Ahmad from Bank of America.

我們的下一個問題來自美國銀行的 Tazeen Ahmad。

I was hoping to get a little bit more detail on the 1 patient that was just dosed today. Maybe if you can share the age of the patient and also how long it took from the time the doctor identified the patient as appropriate for the drug to today. And do you expect that timeline to be representative on a go-forward basis, at least for the next few months, for uptake?

我希望獲得有關今天剛接受給藥的 1 名患者的更多詳細資訊。也許您可以分享患者的年齡，以及從醫生確定患者適合該藥物到今天花了多長時間。您是否認為該時間表在未來的基礎上（至少在接下來的幾個月）具有代表性？

So on the patient, the patient, I believe this was -- I would normally not answer this question because of patient privacy, but I think it's already out on social media. The patient was 1 day away from their sixth birthday. So as you can appreciate, there was an enormous amount of work, not merely on our team's sake, but frankly, on the physician and their staff's part, to ensure that this patient didn't age out. And frankly, kudos to the payer for prioritizing this to ensure this patient received access, which I think speaks -- it speaks to the execution of the team. It speaks to the passion and ability of the physicians that we're working with. And frankly, it speaks to the willingness of payers to provide access and to be thoughtful about patients, which I think is a wonderful answer for all of us.

所以關於病人，病人，我相信這是——因為病人的隱私，我通常不會回答這個問題，但我認為它已經在社交媒體上發布了。距離患者六歲生日還有 1 天。正如您所理解的，為了確保這名患者不會衰老，我們付出了巨大的工作量，不僅是為了我們團隊的利益，而且坦率地說，對於醫生和他們的工作人員來說也是如此。坦白說，值得讚揚的是付款人優先考慮這一點，以確保該患者獲得訪問權，我認為這說明了——它說明了團隊的執行力。它體現了與我們合作的醫生的熱情和能力。坦白說，這表明付款人願意提供服務並為患者著想，我認為這對我們所有人來說都是一個很好的答案。

Looking forward, as I've said before, and I think Dallan reiterated in his remarks, you should assume that the significant ramp in this therapy is going to occur later this year. There are obvious administrative reasons for that. Payers, policies and the -- like have to get completed. And then administratively, we have to release product and that's a dual-release process right now. We release it and then the FDA releases it as well. But as Dallan noted, we do have a handful of patients over the next literally coming few days that are currently scheduled for infusion. But I really want to reiterate, you should look out to really see that ramped infusions later this year.

展望未來，正如我之前所說，而且我認為達倫在他的演講中重申了這一點，你應該假設這種療法的顯著增長將在今年晚些時候發生。這有明顯的行政原因。付款人、保單等都必須完成。然後在管理上，我們必須發布產品，現在這是一個雙重發布流程。我們發布它，然後 FDA 也發布它。但正如達倫指出的那樣，我們確實有少數患者在接下來的幾天內計劃接受輸液。但我真的想重申，你應該留意今年稍後的注入量。

Our next question comes from the line of Gena Wang from Barclays.

我們的下一個問題來自巴克萊銀行的 Gena Wang。

I will also ask the peer questions. So based on your initial interaction with all the hospitals, how many of these like DMD patients approaching 6 years old? And what strategy you have tried to treat those patients before payers' policy in place? And is there a way you can book revenue before the payer policy in place?

我也會向同行詢問問題。那麼根據您與所有醫院的初步互動，其中有多少像接近 6 歲的 DMD 患者？在付款人政策到位之前，您嘗試過什麼策略來治療這些患者？有沒有辦法可以在付款人政策到位之前登記收入？

I apologize. I missed the last part of your question. I'm going to turn this over to Dallan to answer, but you'll see that the strategy, which is not our own strategy alone, but it is a shared strategy with these very passionate physicians working in concert with payers, is to prioritize children ensured they can get access, if at all possible, before they age out of the label. And you saw that poignantly today with the boy who received access today 1 day before a 6 birthday. But Dallan, do you have any other thoughts on that?

我道歉。我錯過了你問題的最後一部分。我會把這個問題交給 Dallan 來回答，但你會看到這個策略，這不僅僅是我們自己的策略，而是這些非常熱情的醫生與付款人合作的共同策略，就是優先考慮孩子們確保他們能夠在可能的情況下在年齡超出標籤範圍之前獲得存取權限。今天，您在 6 歲生日前 1 天收到訪問權限的男孩身上看到了這一點。但是達蘭，你對此還有什麼其他想法嗎？

Yes, Gena, thank you for the question. In the short term, we've been focused on those boys that are turning 6 in the next while. As Doug said in the earnings call, there's an incident population in Duchenne of 400 patients born each year. Now not all of those patients are diagnosed by the age of their sixth birthday. There's actually a pretty good percentage that don't get diagnosed by their sixth birthday. But there is a good number of patients sitting in the sites that are turning 6 and a big focus in terms of our execution. As Doug also said and as we've said before, we aren't guiding around patient numbers. We're going to focus on net revenue as we've done with the other launches.

是的，吉娜，謝謝你的提問。短期內，我們的重點是那些即將滿六歲的男孩。正如 Doug 在財報電話會議上所說，Duchenne 每年有 400 名出生的患者發生事故。現在，並非所有這些患者都是在六歲生日時被診斷出來的。事實上，有相當多的人在六歲生日之前沒有被診斷出來。但現場有大量即將年滿 6 歲的患者，這也是我們執行工作的重點。正如道格也說過以及我們之前說過的那樣，我們不會圍繞著患者數量進行指導。正如我們對其他產品的推出一樣，我們將重點放在淨收入上。

And our next question comes from Salveen Richter from Goldman Sachs.

我們的下一個問題來自高盛的 Salveen Richter。

Congrats as well on treating the first patient here. With regard to the 3.5 standard deviation assumption, recognize that, that's what you saw, I believe, in study 103. I guess, is there anything else that you're using to support that assumption? And in the context of heterogeneity and even with stratification, what would be -- how you're thinking about the impact here if it's higher?

也恭喜您治療了這裡的第一位患者。關於 3.5 標準差假設，請認識到，我相信這就是您在研究 103 中看到的內容。我想，您還有其他東西可以用來支持該假設嗎？在異質性甚至分層的背景下，如果影響更大，您如何看待這裡的影響？

Well, actually, one would actually presume potentially the opposite. So the 3.5 standard deviation was the original powering for EMBARK that considered the historical trials but didn't take into consideration the various tightening of the protocol that occurred with respect to Study 303, 301 or EMBARK to reduce heterogeneity and create more homogeneity. You'll recall we have a very strong ceiling and floor in that trial. You'll recall that we have stratified not only on the basis of NSAA baselines but also on age, the 4- to 5- and 6- to 7-year-old range. You'll recall that we have restricted all of the patients to rise time under 5 seconds.

嗯，實際上，人們實際上可能會做出相反的假設。因此，3.5 個標準差是 EMBARK 的原始動力，它考慮了歷史試驗，但沒有考慮研究 303、301 或 EMBARK 中為減少異質性並創造更多同質性而發生的各種方案收緊。你會記得我們在那次試驗中有一個非常強大的上限和下限。您可能還記得，我們​​不僅根據 NSAA 基線進行分層，還根據年齡（4 至 5 歲和 6 至 7 歲範圍）進行分層。您可能還記得，我們​​已將所有患者的起床時間限制在 5 秒以內。

All of that should theoretically at least reduce heterogeneity, create more homogeneity across the population and reduce standard deviation. But the 3.5 points that Louise mentioned was considered before those. It didn't take those into consideration. And indeed, when the research team did their modeling, they didn't change the standard deviation, so they didn't actually amend that for their modeling purposes. So we feel very good about where we are right now. And then to remind you, the study was powered off of 120 patients with a presumption of some dropouts. We sit here today, the study was overenrolled. It's now 125 patients, and we've had absolutely 0 dropouts and frankly, don't anticipate any dropouts before the last patient last visit, which will occur in mid-September. So we feel very good about where we are right now.

從理論上講，所有這些至少應該減少異質性，在人群中創造更多的同質性並減少標準偏差。但Louise提到的3.5點是在這些之前考慮的。它沒有考慮到這些。事實上，當研究團隊進行建模時，他們沒有改變標準差，因此他們實際上並沒有出於建模目的對其進行修改。所以我們對現在的處境感覺非常好。然後提醒您的是，研究以 120 名患者為對象，並假設有一些患者退出。我們今天坐在這裡，這項研究已經超額報名。現在有 125 名患者，而且我們的中途流失率絕對為零，坦白說，預計在最後一位患者最後一次就診（九月中旬）之前不會有任何中途流失。所以我們對現在的處境感覺非常好。

Our next question comes from the line of Gil Blum from Needham & Company.

我們的下一個問題來自 Needham & Company 的 Gil Blum。

Maybe a bit of a rephrasing on an earlier question here. Is there a situation in what you think the data from EMBARK will be broken up based on age, given potential different feedback from the agency?

也許這裡對之前的問題做了一些改寫。鑑於該機構可能提供不同的回饋，您認為 EMBARK 的數據是否會根據年齡進行細分？

No, no, we don't. The study has been powered to see a treatment effect in the study population, which is 4 to 7. It's very well powered to see that. And we've had conversations with the FDA and FDA leadership, which has confirmed that if we're successful in our trial, they will move rapidly once we've submitted data to them to review that data and to remove the age limitations.

不，不，我們不。該研究已經有說服力地看到了對 4 到 7 名研究人群的治療效果。它非常有力地看到了這一點。我們已經與 FDA 和 FDA 領導層進行了對話，他們確認，如果我們的試驗成功，一旦我們向他們提交數據，他們就會迅速採取行動，審查數據並消除年齡限制。

And our next question comes from the line of Uy Ear from Mizuho.

我們的下一個問題來自 Mizuho 的 Uy Ear。

Congrats on the dosing the first patients. So my question is just referring to what Doug said in the prepared remarks. You said you're going to expand the label in the first half to the majority of patients. Can you kind of elaborate by what you mean by that? Will the older patients and the nonambulatory patients, would those be included? Or would that come much later where I think your goal is to reach 95% of the patients?

祝賀第一批患者接受給藥。所以我的問題只是指道格在準備好的發言中所說的話。您說您將在上半年將標籤擴展到大多數患者。能詳細說明一下您的意思嗎？老年患者和不能走動的患者會被包括在內嗎？或者，我認為你們的目標是涵蓋 95% 的患者，這會發生得更晚嗎？

Yes. Thank you very much for your question. So let's go. There are sort of 2 steps to this. So as we stand here today, we have a label for 4- and 5-year-old patients. When EMBARK is successful, and we have a lot of conviction around EMBARK and the success of EMBARK, we will immediately submit that data to the agency before we've even submitted a BLA supplement with the goal of them beginning the review as soon as they receive that data. Assuming that EMBARK is successful, we would assume that all age limitations will be removed from the label and that gets us to the majority of patients, both ambulatory, nonambulatory and all age ranges. As we've said, we've had conversations with the agency about removing all of the age ranges. There would be no logical basis to assume that ambulation status would be a reason to limit access. It's not as if this protein is aware that a patient is in a wheelchair or not. So we feel very confident about that.

是的。非常感謝您的提問。那我們走吧。這有兩個步驟。因此，當我們今天站在這裡時，我們有一個針對 4 歲和 5 歲患者的標籤。當 EMBARK 成功時，我們對 EMBARK 和 EMBARK 的成功充滿信心，我們將在提交 BLA 補充之前立即向該機構提交這些數據，目標是他們一旦獲得批准就開始審查接收該數據。假設 EMBARK 取得成功，我們將假設所有年齡限制都將從標籤中消除，這將使我們接觸到大多數患者，包括門診、非門診和所有年齡層的患者。正如我們所說，我們已與該機構就刪除所有年齡範圍進行了對話。假設移動狀態將成為限制存取的理由是沒有邏輯依據的。這種蛋白質並不知道患者是否坐在輪椅上。所以我們對此非常有信心。

There is 1 additional thing we'll do, which is we'll take a cut from our current nonambulatory study to have additional safety data that supplements the safety data we already have on the older and nonambulatory patients as well. So that's our goal first early next year to have a broad label that covers all patients. There are 2 -- there will still remain 2 limitations in the ability to receive that therapy. One of them is this 5% or so of mutations that cover exon 8 and/or 9 that are contraindicated for those mutations. That will remain for some time. We're going to continue to do work on that and hopefully narrow that. But for the time being, that will be in the label.

我們還要做一件事，那就是我們將從目前的非臥床研究中抽取一部分，以獲得額外的安全數據，以補充我們已經擁有的關於老年和非臥床患者的安全數據。因此，我們的目標是明年初首先建立一個涵蓋所有患者的廣泛標籤。接受該治療的能力仍有 2 個限制，但仍有 2 個限制。其中之一是 5% 左右的突變覆蓋了外顯子 8 和/或 9，這些突變是禁忌的。這將持續一段時間。我們將繼續在這方面開展工作，並希望縮小範圍。但目前，這將出現在標籤中。

And then the second one is preexisting antibodies. About 13.9% based on our seroprevalence study represent patients that have some environmental exposure to something that looks like an antibody for RA 74. Those patients cannot currently be dosed. But as Dr. Rodino-Klapac mentioned in her prepared remarks, we're starting 2 different alternative approaches to clear those antibodies, one imlifidase, to cleave them and apheresis as a second alternative to clear antibodies. And if one or both of those are successful, then in the near term, we could start presumably empowering physicians to safely and effectively dose even patients that have pre-existing antibodies. That would get us to more than just the majority of patients to potentially as much as 95% of patients. So that's our goal.

第二個是預先存在的抗體。根據我們的血清陽性率研究，約 13.9% 的患者在一定程度上接觸過類似 RA 74 抗體的環境。這些患者目前無法接受給藥。但正如Rodino-Klapac 博士在她準備好的演講中提到的，我們正在開始兩種不同的替代方法來清除這些抗體，一種是酰亞胺酶，用於裂解它們，另一種是血漿分離手術，作為清除抗體的第二種替代方法。如果其中一項或兩項都成功，那麼在短期內，我們可能會開始授權醫生安全有效地給已有抗體的患者用藥。這將使我們不僅能接觸到大多數患者，甚至可能接觸到 95% 的患者。這就是我們的目標。

Our next question comes from the line of Michael Ulz from Morgan Stanley.

我們的下一個問題來自摩根士丹利的 Michael Ulz。

Maybe just another one on the ELEVIDYS launch. In your prepared remarks, you mentioned greater than 50 sites are trained and activated currently. Just curious if you can give us the total number of sites expected? Just trying to get a sense of whether that represents a majority currently or where you're at in that process?

也許只是 ELEVIDYS 推出的另一款產品。在您準備好的發言中，您提到目前有超過 50 個站點經過培訓和啟動。只是好奇您能否向我們提供預計的站點總數？只是想了解這是否代表了目前的大多數，或者您在這個過程中處於什麼位置？

50 sites is a tremendous number of sites. We are -- I am completely thrilled with the team's ability. 50 -- So about 80% of all Duchenne patients are covered by about 50 centers of care in the United States. So 50 sites is an enormous number of sites to infuse ELEVIDYS. Our goal is to get to as many as 70 sites over time, and we're significantly ahead of schedule in our goal to do that. So we're in really, really great shape from a site perspective and Dallan and his team deserve an enormous amount of kudos for where we've gotten right now.

50 個站點是一個龐大的站點數量。我們——我對團隊的能力感到非常興奮。 50 - 因此，美國大約 50 個護理中心涵蓋了約 80% 的杜興氏症患者。因此，50 個網站對於注入 ELEVIDYS 來說是一個巨大的數字。我們的目標是隨著時間的推移覆蓋多達 70 個站點，並且我們已經遠遠提前實現了這一目標。因此，從網站的角度來看，我們的狀態非常非常好，Dallan 和他的團隊應該為我們現在所取得的成就而獲得巨大的榮譽。

Our next question comes from the line of Danielle Brill from Raymond James.

我們的下一個問題來自雷蒙德詹姆斯 (Raymond James) 的丹妮爾布里爾 (Danielle Brill)。

I have a quick follow-up to Salveen's question on the standard deviation. I guess I'm curious, are you able to see blinded SD data or any other blinded data from EMBARK that allows you to stress test your powering assumptions? Just kind of hoping you can elaborate further on your confidence in the assumptions.

我對 Salveen 關於標準差的問題進行了快速跟進。我想我很好奇，您是否能夠看到來自 EMBARK 的盲態 SD 數據或任何其他盲態數據，以便對您的供電假設進行壓力測試？只是希望您能進一步闡述您對這些假設的信心。

We do not have access to -- so looking at the blinded data wouldn't be very insightful, and we don't have access to the unblinded data. So we feel very comfortable with is that our initial study was powered with the standard deviation that we were seeing in studies that did not have the homogenizing restrictions that EMBARK has in it. And yet when we did the simulations, when Louise and her team and our stats group did the simulations to test the powering assumptions and the like, they did not actually take into account the homogenizing aspects of the change in protocol, things like, as I've mentioned before, stratifying on age and making sure that all kids had a rise time under 5 seconds and having strong floors and ceilings and the like. So we feel very good about the powering of the study, and we feel good as we sit here today on the standard deviation. But we haven't had access to unblinded data to test those assumptions.

我們無權存取－因此查看盲資料不會很有洞察力，而且我們也無權存取非盲資料。因此，我們感到非常滿意的是，我們最初的研究以我們在研究中看到的標準差為動力，這些研究沒有 EMBARK 的同質化限制。然而，當我們進行模擬時，當路易斯和她的團隊以及我們的統計小組進行模擬來測試供電假設等時，他們實際上並沒有考慮到協議變化的同質化方面，就像我之前提到過，按年齡分層，確保所有孩子的起床時間都在5 秒以內，並擁有堅固的地板和天花板等。因此，我們對這項研究的動力感到非常滿意，今天我們坐在這裡討論標準差時，我們感覺很好。但我們還沒有獲得非盲數據來測試這些假設。

And our next question comes from the line of Ritu Baral from TD Cowen.

我們的下一個問題來自 TD Cowen 的 Ritu Baral。

Just back to the centers for a second. Doug, can you say if the handful of patients that you were referencing in the next couple of weeks, will they be at 5 different centers and -- of the 50? And then can you talk a little bit about -- are there centers that you expect to move faster than others, maybe given their history with Zolgensma and how comfortable they are? And then if I can squeak another one in. Do you know how many antibody tests have been run? And can you release that?

回到中心一會兒。道格，你能否說一下，如果你在接下來的幾週內提到的少數患者，他們會在 5 個不同的中心，而且是 50 個中心？然後你能談談 - 是否有一些中鋒你希望比其他中鋒移動得更快，也許考慮到他們與 Zolgensma 的歷史以及他們的舒適度？然後我可以再塞入一份嗎？你知道已經進行了多少次抗體測試嗎？你能釋放它嗎？

So I don't know the last answer for you. I can answer the first 2. All of them -- so all of the handful are at different sites. So they're broadly across different sites. And then if any sites are faster, the good news on these -- first of all, the amount of passion from the physicians is really wonderful. And everyone's trying to move as fast as possible to get kids infused and benefit these kids, particularly kids that might otherwise age out. We have really benefited and the team has really benefited from the fact that these -- most of these sites, the majority of these sites have had experience with Zolgensma and know how to infuse gene therapies. So they were well prepared before we went in and got the process of initiating them and getting them site ready. So I would say broadly speaking, there's a lot of enthusiasm to move as fast as reasonably possible to get patients benefiting from ELEVIDYS.

所以我不知道你的最後答案。我可以回答前兩個問題。所有這些問題都在不同的地點。所以它們廣泛分佈在不同的站點。然後，如果有任何網站速度更快，那麼這些網站的好消息是——首先，醫生的熱情真的很棒。每個人都在努力盡快採取行動，讓孩子融入並造福這些孩子，尤其是那些可能會變老的孩子。我們確實受益匪淺，團隊也確實受益於這樣一個事實：這些站點中的大多數站點都有 Zolgensma 的經驗，並且知道如何注入基因療法。因此，在我們進入並啟動他們並準備好現場之前，他們已經做好了充分的準備。因此，我想說，從廣義上講，人們非常熱衷於盡可能快地採取行動，讓患者從 ELEVIDYS 中受益。

Yes, and in terms of the antibody testing, it's going smoothly and functioning well, and we aren't disclosing the numbers right now, but it is working well and going smoothly. And we're happy with the demand.

是的，就抗體測試而言，它進展順利且運作良好，我們現在沒有透露具體數字，但它運作良好且進展順利。我們對需求感到滿意。

Our next question comes from the line of Anupam Rama from JPMorgan.

我們的下一個問題來自摩根大通的 Anupam Rama。

Just a clarification point. Sorry if I missed this. What are the gating factors to starting the SRP-9003 pivotal study later this year?

只是一個澄清點。抱歉，如果我錯過了這個。今年稍後啟動 SRP-9003 關鍵研究的限制因素是什麼？

I'll turn this over to Louise without getting any of it wrong, but I think it's all just CMC and manufacturing, if I'm not mistaken. But Louise, you tell me if I'm missing a nuance.

我會把它交給 Louise，不會出錯，但如果我沒記錯的話，我認為這只是 CMC 和製造。但是路易絲，你告訴我我是否錯過了細微差別。

No, that's accurate. Just making sure the release assays are in place and we're all set. But we -- as we mentioned, we fully enrolled Journey and have a great deal of patients lined up, and most of them having natural history data as well.

不，這是準確的。只要確保釋放檢測到位並且一切準備就緒即可。但正如我們所提到的，我們完全註冊了 Journey，並且有大量患者排隊，其中大多數人也擁有自然歷史數據。

And our next question comes from the line of Joseph Schwartz from Leerink Partners.

我們的下一個問題來自 Leerink Partners 的 Joseph Schwartz。

This is Will on for Joe today. I'll add my congrats on the progress this quarter. So one for us, wondering what the opportunity is for SRP 5051 relative to the PMOs that you currently market. Is this a potential franchise expander? And are there any reasons why a patient is not currently on a PMO, but would be a candidate for PPMO?

這是威爾今天為喬做的節目。我將對本季度的進展表示祝賀。因此，我們想知道 SRP 5051 相對於您目前銷售的 PMO 有何機會。這是一個潛在的特許經營擴張者嗎？患者目前沒有參加 PMO，但會成為 PPMO 的候選者，是否有任何原因？

So not on it. So I think, broadly speaking, if it was successful, so we'll see the data later this year, and then we'll -- if we're successful with the data later this year and the risk benefit justifies it, we're going to seek an NDA for 5051 next year. The goal then would be -- there's a couple of things. The first goal is that it would be more convenient and potentially much more powerful version of our PMOs. So for patients already on the therapy, it would be a great transition to this therapy for them and benefit them. You could envision in the United States, we might have even -- we've had a great success record with access. We might have even greater success with access if we were making 3%, 4%, 5%, which would be multiple folds more dystrophin than the PMOs. And then it does always offer the theoretical opportunity to move outside of the United States, which is something we're very excited to do, which is bringing our RNA technology more broadly around the world to benefit patients. So there's a lot of potential opportunity with the PPMOs, if successful. So we're looking forward to looking at the Part B of momentum later this year and then making some decisions across the portfolio and aggressively bringing things forward if we see success with 5051.

所以不就它了。所以我認為，從廣義上講，如果它成功了，那麼我們將在今年晚些時候看到數據，然後我們會- 如果我們在今年晚些時候獲得成功的數據並且風險收益證明了這一點，我們將明年我們將尋求 5051 的 NDA。那麼目標就是──有幾件事。第一個目標是，它將成為我們 PMO 的更方便且可能更強大的版本。因此，對於已經接受治療的患者來說，這對他們來說將是一個很好的過渡，並使他們受益。你可以想像在美國，我們甚至可能在訪問方面取得了巨大的成功記錄。如果我們生產 3%、4%、5%（這將是 PMO 的數倍），我們可能會在獲取方面取得更大的成功。然後，它確實總是提供理論上的機會，讓我們走出美國，這是我們非常高興做的事情，這將我們的 RNA 技術更廣泛地推廣到世界各地，造福患者。因此，如果成功的話，專案管理辦公室將有很多潛在的機會。因此，我們期待今年稍後看到勢頭的 B 部分，然後在整個投資組合中做出一些決定，如果我們看到 5051 取得成功，我們將積極推動事情向前發展。

And our next question comes from the line of Kristen Kluska from Cantor Fitzgerald.

我們的下一個問題來自康托·菲茨杰拉德 (Cantor Fitzgerald) 的克里斯汀·克魯斯卡 (Kristen Kluska)。

Congrats on today's milestone. Given that you're taking all these steps now across sites, payers and antibody testing, is it your expectation that if you end up getting a broader label in the first half of next year, that the 3- to 4-month timeline you've commuted -- you've communicated to us in terms of patients getting on therapy could be shortened?

祝賀今天的里程碑。鑑於您現在正在跨網站、付款人和抗體測試採取所有這些步驟，您是否期望，如果您最終在明年上半年獲得更廣泛的標籤，那麼您的 3 到 4 個月的時間表已經通勤了——您已經與我們溝通過患者接受治療的時間可以縮短嗎？

Yes. The answer is generally speaking, yes. This really is an initiation issue with the launch of the therapy, policies have to be in place. In some places, codes have to be in place and the like. And then, of course, we have this current release process. So we ought to be in a position to move faster over time. But as I said before, we've had a lot of very fantastic early success but we should assume that the real ramp begins later this year.

是的。一般來說，答案是肯定的。這確實是治療啟動的啟動問題，政策必須到位。在某些地方，必須有代碼等。當然，我們還有目前的發布流程。因此，隨著時間的推移，我們應該能夠更快地採取行動。但正如我之前所說，我們已經取得了許多非常出色的早期成功，但我們應該假設真正的進步將在今年稍後開始。

And our next question comes from the line of Tim Lugo from William Blair.

我們的下一個問題來自威廉·布萊爾的蒂姆·盧戈。

This is John on for Tim. So I was just wondering beyond the effort that the team is making to get access to patients approaching 6 years of age, just wondering if you could talk a little bit about any higher demand you're seeing from the patients approaching that age cutoff and if you're seeing more patient starts from those patients.

這是約翰替提姆發言。因此，我只是想知道，除了團隊為接觸接近6 歲的患者所做的努力之外，我只是想知道您是否可以談談您從接近該年齡界限的患者那裡看到的任何更高的需求，以及是否可以你會看到更多的病人從這些病人開始。

I'll turn this over to Dallan.

我會把這個交給達蘭。

Yes. Thanks for the question. We're seeing demand broadly in both the 4- and 5-year-old age group. In terms of access early on, it is skewing heavily to those patients that are going to have the birthdays and just more so maybe because of the urgency and the dialogue that's happening between KOLs, payers and the teams right now. So early on, yes, we are seeing it skewed towards 6-year -- the people with birthdays turning 6, but we expect that to normalize very quickly as we start to work towards all of the patients that are eligible, that 4 to 5 age group.

是的。謝謝你的提問。我們看到 4 歲和 5 歲年齡層的需求廣泛。就早期訪問而言，它嚴重偏向那些即將過生日的患者，更可能是因為緊迫性以及 KOL、付款人和團隊之間正在進行的對話。是的，我們很早就看到它偏向6 歲——生日已滿6 歲的人，但我們預計，隨著我們開始針對所有符合資格的患者（即4 到5 歲），這種情況會很快恢復正常。年齡階層。

So we're seeing demand in start forms across the ages. We'll likely get access skewing to the older kids in that age range for the obvious reason that we want to get them dosed before there's an issue with the label.

因此，我們看到了各個年齡層對起始形式的需求。我們可能會偏向該年齡層的年齡較大的孩子，原因很明顯，我們希望在標籤出現問題之前讓他們服藥。

Yes.

是的。

And our next question comes from the line of Brian Skorney from Baird.

我們的下一個問題來自貝爾德 (Baird) 的布萊恩·斯科尼 (Brian Skorney)。

This is Luke on for Brian. Regarding the pace of progress getting the ENVISION trial up and running, have you seen any signals that the availability of commercial products might be a headwind to enrollment in the ambulatory population?

這是盧克為布萊恩代言的。關於 ENVISION 試驗的啟動和運行進展速度，您是否看到任何跡象表明商業產品的可用性可能會阻礙流動人群的註冊？

The answer to that is going to be no. So we were very thoughtful about the protocol for ENVISION. In fact, we've significantly limited the number of patients that are going to come out of the United States to ensure that we don't have an issue with the progress of that therapy as we broaden the label. Now that does mean that the enrollment for ENVISION will move slower than for instance, EMBARK, which rapidly enrolled as everyone may recall. But ultimately, we're not seeing an impact from this approval on that basis and part of it is because we're going to enroll the majority of subjects outside of the United States.

答案是否定的。因此，我們對 ENVISION 的協議進行了非常深思熟慮。事實上，我們已經大大限制了從美國出來的患者數量，以確保我們在擴大標籤範圍時不會對該療法的進展產生問題。現在，這確實意味著 ENVISION 的註冊速度將比 EMBARK 慢，每個人都記得 EMBARK 的註冊速度很快。但最終，我們並沒有看到這項批准的影響，部分原因是我們將在美國境外招收大多數科目。

And our final question for today comes from the line of Debjit Chattopadhyay from Guggenheim.

我們今天的最後一個問題來自古根漢的 Debjit Chattopadhyay。

What is the current gross margin for ELEVIDYS? And where do you think it will migrate either on peak capacity or if you could successfully migrate to the 1,000-liter scale?

ELEVIDYS 目前的毛利率是多少？您認為它會在峰值容量下遷移到哪裡，或者如果您能成功遷移到 1,000 公升規模？

Sure. I'll turn this over to Ian.

當然。我會把這個交給伊恩。

Sure. So we've said that we would expect the margins to be like high-quality targeted agents, so kind of in that 80% range similar to what we're seeing with our PMOs. Now obviously, it's going to be higher when the earlier patients are being dosed. And then as heavier patients then we expand the label trend down, but basically into kind of that 80% range. And then obviously, to your good point, we could see a big change. We're not in a position to quantify that from where we are from a manufacturing perspective on our suspension process. But obviously, it has -- to Doug's point, a big impact on our yield. And so we could see that driving that number higher. But obviously, we're not willing to commit to that just yet.

當然。所以我們說過，我們預期利潤率會像高品質的目標代理商一樣，在 80% 的範圍內，類似於我們在 PMO 中看到的情況。現在顯然，當較早的患者接受給藥時，它會更高。然後，對於較重的患者，我們將標籤趨勢向下擴展，但基本上進入 80% 的範圍。顯然，就你的觀點而言，我們可以看到巨大的變化。我們無法從製造角度對懸吊過程進行量化。但顯然，在道格看來，它對我們的產量產生了重大影響。所以我們可以看到這推動了這個數字的上升。但顯然，我們還不願意做出承諾。

Thank you. This does conclude the question-and-answer session of today's program. I'd like to hand the program back to management for any further remarks.

謝謝。今天節目的問答環節到此結束。我想將該程序交還給管理層以徵求進一步的意見。

Thank you, Jonathan, and thank you, everyone, for joining us this evening and for your questions. I appreciate it. We've obviously made, from my perspective, great progress so far this year, both with the approval of ELEVIDYS and then serving patients, both with ELEVIDYS and with our existing PMOs. I will remind us that the team has done a brilliant job of continuing to serve the community with our PMOs. And we are -- we feel very confident about our current guidance on the PMOs. We have a lot to do for the rest of the year, both serving these patients, continuing to serve the patients with the PMOs, getting the EMBARK readout about which we have an enormous amount of conviction, and then we will share that with you at essentially at the same time that we share with our colleagues at the FDA. And our goal, of course, is to broaden this label as soon as reasonably possible and bring ELEVIDYS to the vast majority of patients living with Duchenne and their families. With that, I look forward to updating everyone over the course of the quarter, and I would ask everyone to have a lovely evening.

謝謝喬納森，也謝謝大家今晚加入我們並提出問題。我很感激。從我的角度來看，今年到目前為止，我們顯然已經取得了巨大進展，無論是 ELEVIDYS 的批准，還是透過 ELEVIDYS 和我們現有的 PMO 為患者提供服務。我要提醒我們的是，團隊在繼續與我們的 PMO 一起為社區服務方面做得非常出色。我們對目前對專案管理辦公室的指導非常有信心。今年剩下的時間裡，我們還有很多工作要做，既要為這些患者提供服務，又要繼續為 PMO 的患者提供服務，還要獲得我們堅信的 EMBARK 讀數，然後我們將與您分享：基本上是在同一時間我們與FDA 的同事分享。當然，我們的目標是盡快擴大這個標籤，並將 ELEVIDYS 帶給絕大多數與 Duchenne 一起生活的患者及其家人。至此，我期待在本季向大家通報最新情況，並祝大家度過一個愉快的夜晚。

Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.

女士們、先生們，感謝你們參加今天的會議。這確實結束了該程式。您現在可以斷開連線。再會。