Sarepta Therapeutics Inc (SRPT) 2023 Q4 法說會逐字稿

Good afternoon, and welcome to the Sarepta Therapeutics Fourth Quarter and Full Year 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 年第四季和全年財報電話會議。 （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, Shannon, and thank you all for joining today's call.

謝謝香農，也謝謝大家參加今天的電話會議。

Earlier this afternoon, we released our financial results for the fourth quarter and full year 2023. 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.

今天下午早些時候，我們發布了2023 年第四季度和全年的財務業績。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。

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.

今天加入我們電話會議的有道格·英格拉姆 (Doug Ingram)、伊恩·埃斯特潘 (Ian Estepan)、達蘭·穆雷 (Dallan Murray)；和路易絲·羅迪諾-克拉帕克博士。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, the 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 annual report on Form 10-K 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，我們建議您查看該公司向 SEC 提交的最新 10-K 表格年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, Fran. By the way, everyone, it was Fran's birthday yesterday. So happy birthday Fran. And good afternoon, everyone, and thank you for joining Sarepta Therapeutics Fourth Quarter 2023 Financial Results Conference Call.

謝謝你，弗蘭。對了，各位，昨天是芙蘭的生日。弗蘭生日快樂。大家下午好，感謝您參加 Sarepta Therapeutics 2023 年第四季財務業績電話會議。

Led by an exceptional launch of ELEVIDYS and continuing performance of our approved PMOs EXONDYS, VYONDYS and AMONDYS, we announced this afternoon, another strong quarter of full year growth and quarterly growth as we serve the patient community. As we preannounced in January at the JPMorgan conference, fourth quarter total net product revenue came in at $365.1 million, growing some 55% over the same quarter of prior year and full year net product revenue achieved $1.14 billion, growing 36% over the prior year.

在 ELEVIDYS 的出色推出以及我們批准的 PMO EXONDYS、VYONDYS 和 AMONDYS 的持續表現的帶動下，我們今天下午宣布，在我們為患者社區服務的過程中，又一個強勁的季度全年增長和季度增長。正如我們一月份在摩根大通會議上預先宣布的那樣，第四季度產品淨收入總額為 3.651 億美元，比去年同期增長約 55%，全年產品淨收入達到 11.4 億美元，比去年同期增長 36% 。

In addition to continuing strong performance among our 3 approved therapies, ELEVIDYS performance was particularly impressive and reflects first-in-class launch excellence. Notwithstanding a label limited to 4- and 5-year-olds representing only about 3% or so of the total Duchenne population, ELEVIDYS net product revenue was $131.2 million for the quarter, and over $200 million for the full year. I'm exceptionally proud of the team's performance here, which speaks to our level of preparation and attention to detail, expert understanding of all aspects of launching innovative rare disease therapies and, of course, our passion for bringing a better life to those living with Duchenne.

除了在我們的 3 種核准療法中繼續保持強勁表現外，ELEVIDYS 的表現尤其令人印象深刻，體現了一流的上市卓越性。儘管該品牌僅限於 4 歲和 5 歲兒童，僅佔杜興人口總數的 3% 左右，但 ELEVIDYS 該季度產品淨收入為 1.312 億美元，全年超過 2 億美元。我對團隊在這裡的表現感到非常自豪，這證明了我們的準備水平和對細節的關注，對推出創新罕見病療法各個方面的專家理解，當然，還有我們為那些患有罕見疾病的人帶來更好生活的熱情杜興。

Dallan Murray, our Chief Customer Officer, will speak to this in his remarks shortly.

我們的首席客戶長 Dallan Murray 很快就會在他的演講中談到這一點。

We also continue to exercise the discipline of a fully integrated commercial stage biotech organization. We were profitable on a GAAP basis in the fourth quarter, having achieved non-GAAP profitability in the third quarter of 2023. And we exited 2023 with approximately $1.7 billion of cash, cash equivalents, restricted cash and investments on our balance sheet.

我們也繼續遵守完全整合的商業階段生物技術組織的紀律。我們在2023 年第三季實現了非GAAP 獲利，並在2023 年第三季實現了非GAAP 獲利。到2023 年，我們的資產負債表上約有17 億美元的現金、現金等價物、限制性現金和投資。

Our CFO, Ian Estepan, will provide more color on financial performance shortly.

我們的財務長 Ian Estepan 很快就會提供更多有關財務業績的資訊。

We also advanced our pipeline in the fourth quarter. In the fourth quarter, we submitted a BLA supplement for ELEVIDYS with the goal of both expanding the label by removing age and ambulation restriction and transitioning our approval from accelerated to traditional. And in February of this year, the FDA accepted our BLA supplement for review and set June 21 as our target review completion date.

我們還在第四季度推進了我們的管道。在第四季度，我們提交了 ELEVIDYS 的 BLA 補充，其目標是透過取消年齡和行走限制來擴大標籤，並將我們的批准從加速過渡到傳統。今年 2 月，FDA 接受了我們的 BLA 補充審查，並將 6 月 21 日定為我們的目標審查完成日期。

In the fourth quarter, we also commenced EMERGENE, our trial for SRP-9003 to treat LGMD Type 2E. Also in January of this year, we announced the positive results of our trial MOMENTUM Part B, investigating the use of our next-generation peptide conjugated PMO, SRP-5051 to treat Duchenne patients that are exon 51 amenable.

在第四季度，我們也開始了 EMERGENE，這是我們使用 SRP-9003 治療 2E 型 LGMD 的試驗。同樣在今年 1 月，我們宣布了 MOMENTUM B 部分試驗的積極結果，該試驗研究了使用我們的下一代肽綴合 PMO SRP-5051 來治療外顯子 51 適合的 Duchenne 患者。

Dr. Louise Rodino-Klapac, our Head of Research and Development, will provide more color on our pipeline progress shortly.

我們的研發主管 Louise Rodino-Klapac 博士很快將提供更多有關我們管道進展的資訊。

In 2017, starting with 1 approved therapy, $5 million in sales, a modest pipeline, a short cash runway and a little more than ambition and grit, we set out to build a sustainable, mature biotech organization, improve the lives of the greatest possible number of Duchenne patients along the way and to become the leaders in the use of RNA and gene therapy to treat rare genetic disease. If we are successful in our plans this year, we will have achieved that vision. From there, we can and we will expand our ambition. And relying on our scientific and financial strength, we intend to advance our internal pipeline but also to bring in external innovation to grow from here, not incrementally but in great multiples. In short, 2024 is going to be a very important year.

2017 年，從1 種核准療法、500 萬美元銷售額、適度的產品線、較短的現金跑道以及雄心壯志和毅力開始，我們著手建立一個可持續、成熟的生物技術組織，改善盡可能多的人的生活一路走來，幫助了許多 Duchenne 患者，並成為使用 RNA 和基因療法治療罕見遺傳疾病的領導者。如果我們今年的計劃成功，我們就實現了這個願景。從那時起，我們能夠而且將會擴大我們的雄心。依靠我們的科學和財務實力，我們打算推進我們的內部管道，同時引入外部創新，從這裡開始成長，不是增量而是成倍增長。簡而言之，2024年將會是非常重要的一年。

And with that, I will turn the call to our Chief Customer Officer, Dallan Murray. Dallan?

接下來，我將把電話轉給我們的首席客戶長 Dallan Murray。達蘭？

Thank you, Doug, and good afternoon.

謝謝你，道格，下午好。

The fourth quarter of 2023 represented a strong finish to an already impressive year as the team generated over $1 billion in net product revenue, a milestone for Sarepta. As previously noted, net product revenue for 2023 totaled $1.14 billion, consisting of roughly $945 million from our PMO franchise and $200 million from the launch of ELEVIDYS, the first gene therapy approved for patients with Duchenne muscular dystrophy. Each of these accomplishments stands on their own merits and the performance of both surpassed our internal projections and external consensus.

2023 年第四季為已經令人印象深刻的一年畫上了圓滿的句號，該團隊創造了超過 10 億美元的淨產品收入，這對 Sarepta 來說是一個里程碑。如前所述，2023 年的產品淨收入總計11.4 億美元，其中約9.45 億美元來自我們的PMO 特許經營權，2 億美元來自ELEVIDYS 的推出，ELEVIDYS 是第一個被批准用於杜氏肌肉營養不良症患者的基因療法。這些成就中的每一項都有其自身的優點，而兩者的表現都超出了我們的內部預測和外部共識。

In the seventh year of our PMO franchise, we again grew net product revenue by double digits from the nearly $844 million in net product revenue from 2022. As with previous years, we delivered this growth organically without taking price increases on any of our approved PMO products. As such, this growth represents an increase in the number of patients we are serving, reflecting our commitment to the Duchenne community.

在我們PMO 特許經營權的第七年，我們的產品淨收入再次實現了兩位數的成長，而2022 年的產品淨收入接近8.44 億美元。與前幾年一樣，我們有機地實現了這一增長，而沒有對任何經批准的PMO 提價。產品。因此，這種增長代表了我們所服務的患者數量的增加，反映了我們對杜興社區的承諾。

Turning to ELEVIDYS. We're extremely pleased with the launch of execution, exceeding our own lofty expectations. In fact, the $200 million in net product revenue surpassed the combined 2023 revenue of the other 5 gene therapy launches from the past 18 months, remarkable given the ELEVIDYS approval occurred just this past summer. The success of ELEVIDYS shows that gene therapy can be commercially viable, providing hope for those patients with Duchenne and for all those with genetic conditions with unmet need.

轉向ELEVIDYS。我們對執行的啟動感到非常高興，超越了我們自己的崇高期望。事實上，2 億美元的產品淨收入超過了過去 18 個月內推出的其他 5 種基因療法在 2023 年收入的總和，考慮到 ELEVIDYS 剛剛在去年夏天獲得批准，這一點非常引人注目。 ELEVIDYS 的成功表明基因療法在商業上是可行的，為 Duchenne 患者和所有患有遺傳性疾病但需求未得到滿足的患者帶來了希望。

While revenue is how we quantify the success of this launch externally, we measure ourselves on how we support patients. Our preparation was deliberate and intense and our process was put to the test with the narrow label. The team responded to that challenge with an incredible commitment to supporting all eligible 4- to 5-year-old patients.

雖然收入是我們在外部量化此次發布成功的方式，但我們衡量自己的標準是我們如何支持患者。我們的準備工作是經過深思熟慮和緊張的，我們的流程也經過了狹窄標籤的測試。該團隊以令人難以置信的承諾來應對這項挑戰，支持所有符合條件的 4 至 5 歲患者。

This was our fourth Duchenne launch, and our knowledge and experience played a significant role in how the team rallied, worked together and rapidly supported those patients who are approaching their sixth birthday and who are at risk of becoming ineligible for therapy. Ensuring no eligible patients are left behind is what motivates us.

這是我們的第四次杜氏啟動，我們的知識和經驗在團隊如何團結、合作和快速支持那些即將六歲生日且有可能不符合治療資格的患者方面發揮了重要作用。確保不遺漏符合條件的患者是我們的動力。

Let's now review the results from the fourth quarter, starting with ELEVIDYS. Net product revenue for the quarter was roughly $131 million. This represented a nearly 90% increase over Q3. We are pleased with our penetration into the very small and narrow segment of the Duchenne population.

現在讓我們回顧一下第四季度的結果，首先是 ELEVIDYS。該季度產品淨收入約為 1.31 億美元。這比第三季度增長了近 90%。我們很高興能夠滲透到杜興人口中非常小而狹窄的部分。

This 4- to 5-year-old label has presented a number of unique executional challenges that are relevant moving forward. Firstly, a significant proportion of the patients in this age group are not yet diagnosed. Given that the average age of diagnosis is around 5 in the United States. Secondly, those who are diagnosed have not had a lot of time to be fully educated about Duchenne, which means the patients and families need to understand that diagnosis, become aware of therapy options go through a more involved and longer pretreatment process than the PMOs, one example of this being antibody testing. And on top of this, the patients must also secure access to ELEVIDYS in this very short time window. Our team has found themselves in a race against time to help these patients. And finally, the relatively small number of diagnosed 4- to 5-year-old patients results in a situation in which we will be working through this prevalent population quickly within the first half of the year.

這個已有 4 到 5 年歷史的品牌提出了許多與未來相關的獨特執行挑戰。首先，這個年齡層的患者中有很大一部分尚未得到診斷。鑑於美國的平均診斷年齡約為 5 歲。其次，那些被診斷出的人沒有太多時間接受有關 Duchenne 的充分教育，這意味著患者和家屬需要了解該診斷，了解治療方案，比 PMO 經歷更複雜和更長的預處理過程，抗體測試就是一個例子。除此之外，患者還必須在這個非常短的時間窗口內確保獲得 ELEVIDYS。我們的團隊發現自己正在與時間賽跑來幫助這些患者。最後，由於確診的 4 至 5 歲患者數量相對較少，因此我們將在今年上半年迅速解決這一流行人群。

On the flip side, many of these dynamics are reversed once patients have transitioned over to the decline phase of the disease. This is illustrated by our real-world experience with the PMOs where we see a larger proportion treated in the older age groups, which is on top of a larger diagnosed patient pool. Because of all this, we do not expect to see significant additional growth within the existing population through the first half of this year. Notably, however, by the time of label expansion, we expect to have cleared the way for those older patients to get dosed as rapidly as possible upon eligibility. I would caution analysts therefore, to not use this current younger population as a frame of reference for our market potential in the overall population. The team is preparing as we speak, for a broad label with a focus on building upon the successful launch execution to date, and we have the access and capacity in place to execute successfully on any broader label scenario.

另一方面，一旦患者過渡到疾病的衰退階段，許多動態就會逆轉。我們在 PMO 的實際經驗中就說明了這一點，我們發現老年族群中接受治療的比例更大，而診斷患者群體也更大。因此，我們預計今年上半年現有人口不會有顯著的額外成長。然而值得注意的是，到標籤擴展時，我們預計已經為那些符合資格的老年患者盡快接受給藥掃清了道路。因此，我要提醒分析師，不要使用目前的年輕人口作為我們在整體人口中的市場潛力的參考框架。正如我們所說，該團隊正在為一個廣泛的標籤做準備，重點是在迄今為止成功的發布執行的基礎上進行構建，並且我們擁有在任何更廣泛的標籤場景中成功執行的訪問權限和能力。

Let's now take a look at the PMO franchise as a whole. As previously mentioned, 2023 net product revenue of $945 million exceeded our full year guidance of $925 million. This performance represents solid revenue growth across all 3 brands, in fact, both VYONDYS 53 and AMONDYS 45 continued their double-digit growth trajectory.

現在讓我們從整體來看 PMO 特許經營權。如前所述，2023 年產品淨收入為 9.45 億美元，超過了我們全年指引的 9.25 億美元。這項業績代表了所有 3 個品牌收入的穩健成長，事實上，VYONDYS 53 和 AMONDYS 45 都繼續保持兩位數的成長軌跡。

Looking now at the fourth quarter of 2023, the team delivered roughly $234 million in net product revenue. This is flat versus Q4 of 2022 net product revenue of roughly $236 million. As you may recall from our Q4 2022 earnings call, we cautioned around keeping the guidance of $925 million for the year due to an increase in the quarter-to-quarter lumpiness that we were observing at that time. Looking now in retrospect, it's clear PMO has performed exactly as we expected and guided. And finally, the performance we just discussed in our PMO business was achieved despite the incredible effort on the ELEVIDYS launch. Notably, we saw minimal impact on our PMO business from ELEVIDYS cannibalization in 2023, given the narrow age range.

現在來看 2023 年第四季度，該團隊實現了約 2.34 億美元的產品淨收入。這與 2022 年第四季約 2.36 億美元的產品淨收入持平。您可能還記得我們在 2022 年第四季的財報電話會議上，我們警告稱，由於我們當時觀察到的季度間波動性有所增加，因此應保持今年 9.25 億美元的指導。現在回想起來，很明顯 PMO 的表現完全符合我們的預期和指導。最後，儘管在 ELEVIDYS 的推出上付出了令人難以置信的努力，但我們剛剛在 PMO 業務中討論的業績實現了。值得注意的是，鑑於年齡範圍較窄，我們認為 2023 年 ELEVIDYS 的蠶食對我們的 PMO 業務影響極小。

In closing, in 2023, Sarepta set a new standard for gene therapy launches with ELEVIDYS. We beat external expectations and delivered roughly $200 million. Equally important, we continue to increase the number of patients we support with our PMOs globally. I continue to be immensely proud of our mission-driven team. Combining our PMO and gene therapy businesses, we exceeded $1 billion in net product revenue for the first time, and we have entered 2024 with momentum.

最後，Sarepta 在 2023 年為 ELEVIDYS 的基因療法推出製定了新標準。我們超出了外部預期，交付了大約 2 億美元。同樣重要的是，我們繼續增加全球 PMO 支援的患者數量。我仍然為我們以使命為導向的團隊感到非常自豪。結合我們的 PMO 和基因療法業務，我們的產品淨收入首次突破 10 億美元，並以強勁勢頭進入 2024 年。

And with that, let me turn the call over to our Head of R&D, and Chief Scientific Officer, Dr. Louise Rodino-Klapac. Louise?

接下來，讓我將電話轉給我們的研發主管兼首席科學官 Louise Rodino-Klapac 博士。路易絲？

Thanks, Dallan.

謝謝，達蘭。

2023 was a year of great accomplishment for Sarepta for the advancement of science and for the health and well-being of patients living with rare disease. 2023 will also be remembered as being a defining moment in genetic medicine.

2023 年是 Sarepta 在科學進步以及罕見疾病患者健康和福祉方面取得巨大成就的一年。 2023 年也將被視為基因醫學的決定性時刻。

In June 2023, the FDA granted accelerated approval to ELEVIDYS, first gene therapy to treat Duchenne muscular dystrophy. Since that time, we've been successfully treating ambulatory pediatric patients aged 4 through 5 years with Duchenne who have a confirmed mutation in the DMD gene. And then just about 2 weeks ago, and as Doug mentioned, we were thrilled to announce that the FDA accepted and filed our efficacy supplement for ELEVIDYS. whereby they will now evaluate broadening the approved indication of ELEVIDYS by removing age and ambulation restrictions and converting the ELEVIDYS accelerated approval to a traditional approval.

2023 年 6 月，FDA 加速批准了 ELEVIDYS，這是第一種治療杜氏肌肉營養不良症的基因療法。從那時起，我們已經成功使用 Duchenne 治療 4 至 5 歲的門診兒科患者，這些患者的 DMD 基因已確認突變。就在大約 2 週前，正如 Doug 提到的，我們很高興地宣布 FDA 接受並提交了我們的 ELEVIDYS 功效補充劑。他們現在將評估透過取消年齡和行走限制並將 ELEVIDYS 加速批准轉變為傳統批准來擴大 ELEVIDYS 的批准適應症。

Should we receive accelerated approval for ELEVIDYS in the non-ambulant population in the United States, our ENVISION study, also called SRP-9001-303 will serve as our confirmatory study for this population. Envision is a global, randomized, double-blind, placebo-controlled 2-part study, evaluating the safety and efficacy of delandistrogene moxeparvovec gene therapy in nonambulatory and older ambulatory individuals with Duchenne. This study is ongoing with all remaining patients being enrolled outside of the United States. With U.S. enrollment completed and the remaining 85% of recruitment occurring ex U.S., we are confident in our ability to complete this trial.

如果我們在美國非流動人群中獲得 ELEVIDYS 的加速批准，我們的 ENVISION 研究（也稱為 SRP-9001-303）將作為我們針對該族群的驗證性研究。 Envision 是一項全球性、隨機、雙盲、安慰劑對照的兩部分研究，評估 delandistrogene moxeparvovec 基因治療對非臥床和老年臥床 Duchenne 患者的安全性和有效性。這項研究正在進行中，所有剩餘患者均在美國境外入組。隨著美國招募工作的完成以及剩餘 85% 的招募工作在美國境外進行，我們對完成這項試驗的能力充滿信心。

Moving now to our limb-girdle muscular dystrophy or LGMD programs. On January 16, we announced that screening was underway in study SRP-9003-301, also known as the EMERGENE study. We are pleased to now share that the first patient has been successfully dosed in that study. To remind you, EMERGENE is a Phase III multinational open-label clinical trial of SRP-9003 for the treatment of limb-girdle muscular dystrophy type 2E or beta-sarcoglycanopathy. The primary endpoint of EMERGENE is expression of beta-sarcoglycan, which is an extremely important endpoint for this program for the other beta-sarcoglycanopathy, including LGMD2D and LGMD2C and for the field of gene therapy. I'll explain why.

現在轉向我們的肢帶型肌肉營養不良症或 LGMD 計畫。 1 月 16 日，我們宣布 SRP-9003-301 研究（也稱為 EMERGENE 研究）正在進行篩選。我們現在很高興地宣布，研究中第一位患者已成功接受給藥。提醒您，EMERGENE 是 SRP-9003 的一項 III 期跨國開放標籤臨床試驗，用於治療 2E 型肢帶型肌肉營養不良症或 β-肌聚醣症。 EMERGENE 的主要終點是 β-肌聚醣的表達，對於該計畫的其他 β-肌聚醣疾病（包括 LGMD2D 和 LGMD2C）以及基因治療領域來說，這是一個極其重要的終點。我會解釋原因。

Beta-sarcoglycanopathy is characterized by a mutation of the beta-sarcoglycan gene, which sits in a complex of a membrane called the sarcoglycan complex and is important for function and for preventing muscle damage during contraction. The sarcoglycan complex is a subcomplex of the dystrophin-associated protein complex or DAPC. A defective sarcoglycan protein results in loss or reduced expression of the other sarcoglycans as well as other proteins in the complex such as dystrophin.

β-肌聚醣複合物的特徵是 β-肌聚醣基因突變，該基因位於稱為肌聚醣複合物的膜複合物中，對於功能和防止收縮過程中的肌肉損傷非常重要。肌聚醣複合物是肌營養不良蛋白相關蛋白質複合物或 DAPC 的子複合物。有缺陷的肌聚醣蛋白會導致複合物中其他肌聚醣以及其他蛋白質的肌肉營養不良蛋白表達缺失或減少。

Therefore, by restoring the missing proteins, such as beta-sarcoglycan, we were able to restore that functional complex at the membrane and thereby restore function to the muscle. Further, earlier this month, I had the opportunity to participate in the Speed Foundation's LGMD scientific workshop, which also featured officials from FDA, including Doctors Mark and Verdun as well as patients, caregivers and clinicians among others. The key takeaways from the workshop included the perspective that traditional trial designs are not suitable for certain types of LGMD and that to ensure these therapies have the best chance of success, the totality of evidence must be considered. Doctors Mark and Verdun also expressed their strong support for regulatory flexibility and a higher tolerance for uncertainty for rare diseases, such as LGMD when you're replacing the native protein as well as support for surrogate endpoints for gene therapies.

因此，透過恢復缺失的蛋白質，例如β-肌聚醣，我們能夠恢復膜上的功能複合物，從而恢復肌肉的功能。此外，本月早些時候，我有機會參加了 Speed 基金會的 LGMD 科學研討會，與會者還包括 FDA 官員，包括馬克醫生和凡爾登醫生以及患者、護理人員和臨床醫生等。研討會的主要收穫包括這樣的觀點：傳統的試驗設計不適合某些類型的 LGMD，為了確保這些療法有最大的成功機會，必須考慮全部證據。馬克和凡爾登醫生也表示強烈支持監管靈活性和對罕見疾病不確定性的更高容忍度，例如替換天然蛋白質時的 LGMD，以及對基因治療替代終點的支持。

Currently, no treatments exist to effectively treat LGMD2E or the other LGMD. The EMERGENE study, which will enroll 15 participants who are ambulatory and nonambulatory, ages 4 and older, not only holds great promise for individuals suffering from LGMD2E but will lay the foundation for our other LGMD programs as well as provide a viable regulatory pathway that supports the development of future gene therapies for rare and ultrarare diseases.

目前，尚無有效治療 LGMD2E 或其他 LGMD 的治療方法。 EMERGENE 研究將招募 15 名 4 歲及以上的能走動和不能走動的參與者，不僅為 LGMD2E 患者帶來巨大希望，而且將為我們其他 LGMD 項目奠定基礎，並提供可行的監管途徑，支持未來針對罕見和超罕見疾病的基因療法的開發。

These data, combined with positive expression and functional data shared from our initial LGMD2E study, SRP-9003 101, which is also published in Nature Medicine earlier this year and our VOYAGENE study, SRP-9003-102, which establishes safety experience across a broader patient population served together as totality of evidence. As a reminder, VOYAGENE is a Phase I study evaluating SRP-9003 for the treatment of LGMD2E in patients ages 18 and older in the ambulant population and ages 4 to 50 in the non-ambulant population. The primary endpoints are safety and change in beta-sarcoglycan expression. We expect to have the clinical results this year.

這些數據與我們最初的LGMD2E 研究SRP-9003 101 和我們的VOYAGENE 研究SRP-9003-102 共享的陽性表達和功能數據相結合，該研究也在今年早些時候發表在《自然醫學》雜誌上，而我們的VOYAGENE 研究SRP-9003-102 在更廣泛的範圍內建立了安全經驗。患者群體一起作為證據的整體。提醒一下，VOYAGENE 是一項 I 期研究，評估 SRP-9003 對 18 歲及以上流動人群和 4 至 50 歲非流動人群中 LGMD2E 患者的治療效果。主要終點是安全性和 β-肌聚醣表現的變化。我們預計今年就能得到臨床結果。

Moving now to our RNA platform. We were also pleased to recently announce positive results from Part B of our MOMENTUM study, the SRP-5051-201. Based on the data we've generated to date, we believe SRP-5051 represents a best-in-class therapy from an efficacy perspective.

現在轉向我們的 RNA 平台。我們最近也很高興地宣布 MOMENTUM 研究 B 部分 SRP-5051-201 的正面結果。根據我們迄今為止產生的數據，我們認為從療效角度來看，SRP-5051 代表了同類最佳的療法。

MOMENTUM is a global multi-ascending dose clinical trial of SRP-5051. Our next-generation peptide phosphorodiamidate morpholino oligomers treatment to patients with Duchenne were amenable to exon 51 skipping. As previously discussed and based on these results, we believe we have a path forward to an NDA and are planning a meeting with the FDA to discuss an accelerated approval. We anticipate that this meeting will occur in the third quarter of 2024.

MOMENTUM 是 SRP-5051 的全球多劑量遞增臨床試驗。我們對 Duchenne 患者進行的下一代勝肽磷酸二醯胺嗎啉寡聚物治療適合外顯子 51 跳躍。正如之前所討論的，基於這些結果，我們相信我們有一條通往 NDA 的道路，併計劃與 FDA 召開會議討論加速批准。我們預計這次會議將於 2024 年第三季舉行。

Regarding our post-marketing studies for the PMOs, as mentioned, we completed enrollment in the ESSENCE trial, our post-marketing requirement for golodirsen and casimersen. As a reminder, ESSENCE is a 2-year study and is due to read out in early 2026. In addition, we are pleased to have completed enrollment in our MIS51ON study, our dose-ranging post-marketing commitment for EXONDYS.

關於我們對 PMO 的上市後研究，如上所述，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。提醒一下，ESSENCE 是一項為期 2 年的研究，將於 2026 年初宣讀。此外，我們很高興完成了 MIS51ON 研究的註冊，這是我們對 EXONDYS 的劑量範圍上市後承諾。

MIS51ON is a randomized double-blind safety and efficacy dose-finding study comparing the approved dosage of eteplirsen, 30 mg per kg weekly through a dosage that provides significantly higher exposure up to 200 mg per kg weekly. MIS51ON is a 2-part Phase III study. It was fully enrolled in October 2023 with 160 patients. We remain committed to rapidly and diligently advancing MIS51ON and sharing data as soon as it becomes available.

MIS51ON 是一項隨機雙盲安全性和有效性劑量探索研究，比較了 eteplirsen 的批准劑量（每週 30 毫克/公斤）與提供顯著更高暴露量（每週每公斤 200 毫克）的劑量。 MIS51ON 是一項由 2 部分組成的 III 期研究。此計畫於 2023 年 10 月全部入組，共有 160 名患者。我們仍然致力於快速、努力地推進 MIS51ON 並在資料可用時立即共享資料。

In conclusion, the months ahead are filled with great promise to advance our mission and serve patients around the world living with rare disease.

總之，未來幾個月充滿了推進我們的使命並為世界各地患有罕見疾病的患者提供服務的巨大希望。

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

我現在將把電話轉給伊恩·埃斯特潘，以了解我們財務表現的最新情況。伊恩？

Thanks, LRK. Good afternoon, everyone.

謝謝，LRK。大家下午好。

This afternoon's financial results press release provided details for the fourth quarter of 2023 on a non-GAAP basis as well as a GAAP basis. Please refer to our press release available on Sarepta's website for a full reconciliation of GAAP to non-GAAP financial results.

今天下午的財務業績新聞稿提供了 2023 年第四季度基於非 GAAP 和 GAAP 的詳細資訊。請參閱 Sarepta 網站上提供的新聞稿，以了解 GAAP 與非 GAAP 財務表現的全面對帳。

Before we get to the results, I just wanted to flag that beginning in the fourth quarter of 2023, amortization of in-license rights and income tax expense or benefit are no longer excluded from non-GAAP results. The company has added income tax effect of adjustments, which represents the estimated income tax impact of each pretax non-GAAP adjustment based on the applicable effective income tax rate.

在我們得出結果之前，我只想指出，從 2023 年第四季開始，許可權攤銷和所得稅費用或福利不再排除在非 GAAP 業績之外。該公司增加了調整的所得稅影響，即根據適用的有效所得稅稅率，每次稅前非公認會計原則調整的估計所得稅影響。

Non-GAAP financial results for the fourth quarter and full year 2022 have been updated to reflect this change for comparability purposes. So for the 3 months ended December 31, 2023, the company recorded total revenues of $396.8 million, which consists of net product revenues and collaboration and other revenues compared to revenues of $258.4 million for the same period of 2022, an increase of $138.4 million.

出於可比性目的，我們對 2022 年第四季度和全年的非 GAAP 財務業績進行了更新，以反映這一變化。因此，截至2023 年12 月31 日的三個月，該公司的總收入為3.968 億美元，其中包括產品淨收入、協作收入和其他收入，與2022 年同期的收入2.584 億美元相比，增加了1.384 億美元。

Net product revenue for the fourth quarter of 2023 from ELEVIDYS was $131.2 million. Net product revenue for the fourth quarter of 2023 from our PMO exon skipping franchise was $233.8 million compared to $235.9 million for the same period of '22 for the fourth quarter of 2023, individual net product sales were $131 million for EXONDYS 51, $69.9 million from AMONDYS 45 and $32.9 million for VYONDYS 53.

ELEVIDYS 2023 年第四季的產品淨收入為 1.312 億美元。 2023 年第四季度，我們的PMO 外顯子跳躍特許經營權的淨產品收入為2.338 億美元，而2023 年第四季度的22 年同期為2.359 億美元，EXONDYS 51 的單一產品淨銷售額為1.31億美元，2023 年第四季的淨產品銷售額為6,990 萬美元。AMONDYS 45 和 VYONDYS 53 分別為 3,290 萬美元。

The increase in net product revenue primarily reflects increasing demand for our PMO products as well as net product revenue associated with sales of ELEVIDYS.

產品淨收入的成長主要反映了對我們的 PMO 產品的需求增加以及與 ELEVIDYS 銷售相關的淨產品收入。

In the quarter ended December 31, 2023, we recognized $31.7 million of collaboration and other revenues compared to $22.5 million for the same period of 2022. This revenue primarily relates to our collaboration arrangement with Roche.

在截至 2023 年 12 月 31 日的季度中，我們確認了 3,170 萬美元的合作和其他收入，而 2022 年同期為 2,250 萬美元。該收入主要與我們與羅氏的合作安排有關。

For the quarter ended December 31, 2023, the company recognized $9.2 million of contract manufacturing collaboration revenue associated with multiple batches of commercial ELEVIDYS supply delivered to Roche with no similar activity ended December 31, 2022.

截至2023年12月31日的季度，該公司確認了與向羅氏交付的多批商業ELEVIDYS供應相關的合約製造合作收入920萬美元，截至2022年12月31日沒有類似活動。

The reimbursable co-development costs under the Roche agreement totaled $23.5 million for the fourth quarter of 2023 compared to $51.7 million for the same period of 2022. On a GAAP basis, we reported net income of $45.7 million or $0.49 per basic and $0.47 per diluted share and a net loss of $109.2 million or $1.24 per basic and diluted share for the fourth quarter of 2023 and 2022, respectively.

2023 年第四季度，羅氏協議下的可報銷共同開發費用總計2,350 萬美元，而2022 年同期為5,170 萬美元。根據GAAP 計算，我們報告的淨利潤為4,570 萬美元，即基本淨利潤為0.49 美元，稀釋淨利為 0.47 美元。2023 年第四季和 2022 年第四季淨虧損為 1.092 億美元，每股基本虧損和稀釋每股虧損 1.24 美元。

We reported non-GAAP net income of $86.6 million or $0.82 per diluted share in the fourth quarter of 2023 compared to a non-GAAP net loss of $53.6 million or $0.61 per diluted share in the fourth quarter of 2022.

我們公佈的 2023 年第四季非 GAAP 淨利潤為 8,660 萬美元，即稀釋後每股 0.82 美元，而 2022 年第四季非 GAAP 淨虧損為 5,360 萬美元，即稀釋後每股 0.61 美元。

In the fourth quarter of 2023, we recorded approximately $44.2 million in cost of sales compared to $30.8 million for the same period of 2022. The increase in cost of sales primarily reflects increasing demand for our PMO products, an increase in royalty payments due to ELEVIDYS sales in 2023, with no similar activity in 2022 and write-off of certain batches of our products not meeting our quality specifications in the 3 months ended December 31, 2023, with no similar activity for the same period of 2022.

2023 年第四季度，我們的銷售成本約為 4,420 萬美元，而 2022 年同期為 3,080 萬美元。銷售成本的增加主要反映了對我們 PMO 產品的需求增加，以及由於 ELEVIDYS 導致的特許權使用費增加2023年的銷售量，2022年沒有類似活動，並註銷了截至2023年12月31日止三個月內不符合品質規格的某些批次產品，2022年同期沒有類似活動。

On a GAAP basis, we recorded $195.5 million and $213.8 million in R&D expenses for the fourth quarter of 2023 and 2022, respectively a year-over-year decrease of $18.3 million. The decrease is primarily due to a decrease in manufacturing expenses and upfront milestone and other expenses. On a non-GAAP basis, R&D expenses were $165.1 million for the fourth quarter of 2023 compared to $186.8 million for the same period of 2022, a decrease of $21.7 million.

以公認會計準則計算，2023 年第四季和 2022 年第四季的研發費用分別為 1.955 億美元和 2.138 億美元，年比減少 1,830 萬美元。減少的主要原因是製造費用以及前期里程碑費用和其他費用的減少。以非公認會計原則計算，2023年第四季的研發費用為1.651億美元，較2022年同期的1.868億美元減少了2,170萬美元。

Now turning to SG&A. On a GAAP basis, we recorded approximately $131.7 million and $120.5 million of expenses for the fourth quarter of 2023 and 2022, respectively, an increase of $11.2 million. The increase was driven primarily by an increase in professional services and compensation and other personnel expenses, partially offset by a decrease in stock-based compensation.

現在轉向SG&A。根據公認會計原則，我們在 2023 年第四季和 2022 年第四季的支出分別約為 1.317 億美元和 1.205 億美元，增加了 1,120 萬美元。這一增長主要是由於專業服務和薪酬以及其他人事費用的增加，部分被股票薪酬的減少所抵消。

On a non-GAAP basis, the SG&A expenses were $105.7 million for the fourth quarter of 2023 compared to $86.6 million for the same period of 2022, an increase of $19.1 million. On a GAAP basis, we recorded $15.7 million in other income net for the fourth quarter of 2023 compared to $5.5 million for the same period of 2022. The change was primarily due to an increase in the accretion of investment discount net due to an increase in interest rates.

以非公認會計原則計算，2023 年第四季的銷售、一般管理費用為 1.057 億美元，而 2022 年同期為 8,660 萬美元，增加了 1,910 萬美元。根據公認會計原則，我們 2023 年第四季的其他收入淨額為 1,570 萬美元，而 2022 年同期為 550 萬美元。這項變更主要是由於投資折扣淨額增加所致。利率。

We had approximately $1.7 billion in cash, cash equivalents and investments and long-term restricted cash as of December 31, 2023.

截至 2023 年 12 月 31 日，我們擁有約 17 億美元的現金、現金等價物和投資以及長期限制性現金。

So to conclude, we're incredibly pleased to achieve our first quarter of profitability from a GAAP perspective. It is impressive to reach this milestone in just the second quarter of the ELEVIDYS launch and highlights the leverage in our business. For the reasons Dallan outlined, there may be some lumpiness on the bottom line in the first half. That said, with an expansion of the label, we expect to be highly profitable for the full year.

總而言之，從 GAAP 角度來看，我們非常高興能夠實現第一季的獲利。在 ELEVIDYS 推出後的第二季就達到了這一里程碑，令人印象深刻，這凸顯了我們業務的影響力。由於達蘭概述的原因，上半場的底線可能會有些不穩定。也就是說，隨著品牌的擴張，我們預計全年將實現高利潤。

Also, as I previously noted, in preparation to serve the community in the event of the label expansion we are continuing to ramp our manufacturing of ELEVIDYS. This continued investment will be apparent in the first quarter financials and the remainder of the year. We are thrilled to have the resources on hand to continue to build the inventory needed to deliver ELEVIDYS to the Duchenne community.

此外，正如我之前指出的，為了準備在標籤擴展時為社區服務，我們將繼續增加 ELEVIDYS 的生產力度。這種持續的投資將在第一季的財務數據和今年剩餘時間中顯現出來。我們很高興擁有現有資源來繼續建立向 Duchenne 社區提供 ELEVIDYS 所需的庫存。

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

然後，我會將電話轉回給道格開始問答。道格？

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

非常感謝你，伊恩。香農，讓我們開始提問吧。

(Operator Instructions) Our first question comes from the line of Gena Wang with Barclays.

（操作員說明）我們的第一個問題來自巴克萊銀行的 Gena Wang。

I think operator, your voice was cut off, so I don't know how many questions I can ask. I just ask 2 very quick questions. So one is ELEVIDYS. For the proposed label, was that based on FDA feedback or was it purely from Sarepta? And the second, regarding the emerging Phase III study in limb-girdle 2E, was it confirmed with the FDA that 15 patients would be sufficient? And what protein level will be approvable?

我想接線員，你的聲音被切斷了，所以我不知道我還能問多少問題。我只問兩個非常簡短的問題。 ELEVIDYS 就是其中之一。對於擬議的標籤，是基於 FDA 的反饋還是純粹來自 Sarepta？第二，關於正在進行的肢帶2E III期研究，FDA是否確認15名患者就足夠了？什麼蛋白質水平可以被批准？

Yes. Thank you very much for your questions Gena. For the future, it is 1 question per analyst. But I appreciate your questions. Let me answer them.

是的。非常感謝您的提問。對於未來，每位分析師提出 1 個問題。但我很欣賞你的問題。讓我來回答他們。

So the basis for our request to expand the label by removing both the age and adulation restriction. That is driven by the science. I want to be very clear about that. We're in the midst of a review. We're very -- we're pleased with the progress of the review so far, but it's too early right now to give you a substantive view on the division's perspective on that. But our view is that the science and the totality of the evidence supports the label expansion that we've asked for, and it's the right answer from our perspective. It's the right answer from the science. It's the right answer from a policy perspective. And most of all, it's the right answer for patients living with Duchenne muscular dystrophy, which I hope will be all of our North stars in this regard.

因此，我們要求透過取消年齡和崇拜限制來擴大標籤的基礎。這是由科學驅動的。我想非常清楚地說明這一點。我們正在進行審核。我們對迄今為止的審查進展感到非常滿意，但現在就該部門對此的觀點提供實質看法還為時過早。但我們的觀點是，科學和全部證據支持我們所要求的標籤擴展，從我們的角度來看，這是正確的答案。這是科學的正確答案。從政策角度來看，這是正確的答案。最重要的是，這是杜氏肌肉營養不良症患者的正確答案，我希望這將是我們在這方面的所有北極星。

With respect to EMERGENE or EMERGENE, I should say, that -- the protocol for that has been shared with and reviewed with by the FDA, and they have on the basis of there were discussions, including the end of the study, given us their blessing to commence that study. And we'll provide additional information on the level of expression likely to predict the clinical benefit at a later date. I would note in our prior studies, we've got 2 cohorts. We've seen very robust expression of the beta-sarcoglycan protein, the absence of which is the sole and exclusive cause of the degeneration in patients who have LGMD type 2E.

關於 EMERGENE 或 EMERGENE，我應該說，該方案已與 FDA 共享並由 FDA 審查，他們在討論的基礎上，包括研究的結束，給了我們他們的祝福開始這項研究。我們將提供有關可能預測稍後臨床獲益的表達水平的更多資訊。我要指出的是，在我們先前的研究中，我們有兩個隊列。我們已經看到 β-肌聚醣蛋白的表達非常強烈，而該蛋白的缺失是 2E 型 LGMD 患者退化的唯一原因。

Our next question comes from the line of Tazeen Ahmad with Bank of America.

我們的下一個問題來自 Tazeen Ahmad 與美國銀行的電話。

I just wanted to get a sense as you look for the expansion of label and how to model COGS, especially as more patients get on therapy over time and the weight of the patients presumably will go higher as you get to older patients? What's the reasonable range of COGS that we should be assuming?

我只是想了解一下，當您尋求標籤擴展以及如何對COGS 進行建模時，尤其是隨著時間的推移，越來越多的患者接受治療，並且隨著年齡較大的患者，患者的體重可能會更高？我們應該假設的合理銷貨成本範圍是多少？

Yes. Ian, I'll turn this to you.

是的。伊恩，我會把這個轉給你。

Sure. So from a COGS perspective, we've been pretty clear that we're targeting 80% obviously from our financials that we reported today. You see it's much higher than that. But over time, as heavier patients get on the therapy and obviously, our pre-expense inventory is exhaustive you'll see the COGS obviously starts to increase and our margins to start to decline more to that 80% range, which we've been guiding. Obviously, we can't give complete clarity around that because we have a suspension, which could be coming online with a much higher yielding process and time for some of the old or heavier patients to be coming on which would offset their weight. So as we said over time, you see some erosion of the margin from where we currently are, but modeling it around 80% is probably reasonable.

當然。因此，從銷貨成本 (COGS) 角度來看，從我們今天報告的財務數據來看，我們的目標顯然是 80%。你看它比這個高得多。但隨著時間的推移，隨著體重較重的患者開始接受治療，顯然，我們的費用前庫存已經耗盡，您會看到COGS 明顯開始增加，而我們的利潤率開始下降至80% 的範圍，這是我們一直以來的預期指引。顯然，我們無法完全澄清這一點，因為我們有一個暫停，它可能會以更高的產量過程上線，並且為一些年老或體重較重的患者提供時間，這將抵消他們的體重。正如我們所說，隨著時間的推移，您會看到我們目前的利潤率下降，但將其建模為 80% 左右可能是合理的。

Our next question comes from the line of Joseph Schwartz with Leerink Partners.

我們的下一個問題來自 Joseph Schwartz 和 Leerink Partners 的電話。

This is Will on for Joe. Congrats on the great quarter here. So one question for us in manufacturing with the recent acquisition of Catalent by Novo and the expected exploration of your agreement with Catalent at the end of this year, how are you guys thinking about manufacturing moving forward. And then in terms of capacity and the potential for an expanded label this year, are there any potential for supply constraints in the near term?

這是威爾為喬做的事。恭喜這個偉大的季度。因此，隨著 Novo 最近收購 Catalent 以及預計在今年年底與 Catalent 達成的協議，我們在製造業面臨的一個問題是，你們如何看待製造業的發展。那麼就產能和今年擴大標籤的潛力而言，短期內是否有供應限制的可能性？

Yes, thanks for your questions. Well, first of all, I think there might be a misunderstanding of some sort. Let me be very clear. Our agreement with Catalent does not end at the end of this year. We have a long-term relationship with Catalent. They've been very good partners of ours. So there will be, from our perspective, no impact from the acquisition of Catalent by Novo Holdings as we understand it, Novo Holdings would be acquiring the entity as a whole, the GLP-1-related manufacturing, I think, is going to be sold down to Novo Nordisk and then Novo Holdings will hold the rest of Catalent and it'll be run the way it's run today. And we've had -- I had had direct discussions with the senior management at Catalent. I'm quite confident that it is business as usual with them. So we're feeling very good about that.

是的，謝謝您的提問。嗯，首先，我認為這可能存在某種誤解。讓我說得很清楚。我們與 Catalent 的協議不會在今年年底結束。我們與康泰倫特有著長期的合作關係。他們一直是我們非常好的合作夥伴。因此，從我們的角度來看，Novo Holdings 收購 Catalent 不會產生任何影響，據我們了解，Novo Holdings 將收購整個實體，我認為與 GLP-1 相關的製造將是出售給諾和諾德公司，然後諾和控股公司將持有康泰倫特的其餘股份，並將按照今天的方式運作。我與 Catalent 的高階管理層進行了直接討論。我非常有信心他們一切如常。所以我們對此感覺非常好。

And generally, from a supply perspective, I will say what we have done together over the last -- in 2018 at the beginning of this journey from a manufacturing and CMC perspective would be nothing other than miraculous if it wasn't for the fact that it's science and hard work-driven. As we sit here today, we're doing a really brilliant job of serving the community, and we'll be continuing to do a brilliant job of serving the community over the course of this year with our partner, Catalent so we're feeling very good about where we are.

一般來說，從供應的角度來看，我會說我們在過去- 2018 年在這一旅程的開始時共同所做的事情，從製造和CMC 的角度來看，如果不是因為以下事實，那將是奇蹟。這是科學和努力工作驅動的。當我們今天坐在這裡時，我們在服務社區方面做得非常出色，並且我們將在今年與我們的合作夥伴 Catalent 一起繼續在服務社區方面做得非常出色，所以我們感覺非常了解我們所處的位置。

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

我們的下一個問題來自 Gil Blum 與 Needham & Company 的對話。

So I know this may be knowable. But can you remind us what the population divided between ambulatory and nonambulatory patients? And what is kind of the median age for loss of ambulation?

所以我知道這可能是可知的。但您能否提醒我們，門診病患和非門診病患的人口分佈是如何的？喪失行走能力的中位數年齡是多少？

So I can give you the broad strokes. It is about epidemiologically about 50-50 between ambulatory and nonambulatory patients. And Dallan, do you have the recent estimates of the (inaudible) loss of ambulation?

所以我可以給你大概的思路。從流行病學角度來看，流動患者與非流動患者之間的比例約為 50-50。達蘭（Dallan），您有最近對（聽不清楚）行走能力喪失的估計嗎？

You cut out there for a second. Did you say the diagnosed patients?

你停頓一下。你說的是確診患者嗎？

Now I said what is the average age of loss of ambulation.

現在我說喪失行走能力的平均年齡是幾歲。

Average age of loss of ambulation, I think Louise will probably have better data than me, but it would be -- depending on different publications in the 11% to 12% range. Louise, does that sound right?

關於喪失行走能力的平均年齡，我認為 Louise 可能會比我有更好的數據，但實際情況會是這樣——具體取決於不同的出版物，在 11% 到 12% 的範圍內。路易絲，聽起來對嗎？

Yes. Some are slightly earlier. To your point, there are some differences.

是的。有的稍微早一些。就您的觀點而言，存在一些差異。

Our next question comes from the line of Brian Abrams with 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的布萊恩‧艾布拉姆斯 (Brian Abrams)。

This is (inaudible) on for Brian. So maybe I'll ask 1.5 questions, if that's okay, not quite 2. So I guess, can you clarify the application process with respect to ELEVIDYS, I guess, is the conversion to a full approval and the label expansion 2 separate questions before the FDA that have potentially separate time lines, reviews, discussions around them? Can they be separated?

這是布萊恩的（聽不清楚）。所以也許我會問1.5 個問題，如果可以的話，不完全是2 個問題。所以我想，您能否澄清一下ELEVIDYS 的申請流程，我想，是轉換為完全批准和標籤擴展之前的2 個單獨的問題FDA 可能有單獨的時間表、審查和討論嗎？他們可以分開嗎？

And then I guess just related to that, you mentioned in the prepared remarks you're thinking through broad label scenarios. So -- and you mentioned if you get an accelerated approval in the non-ambulatory setting, I guess, is that part of those scenarios? Is that something you've heard from the FDA? Or is this just preparing for all the possibilities?

然後我想與此相關的是，您在準備好的評論中提到您正在考慮廣泛的標籤場景。那麼，您提到如果您在非流動環境中獲得加速批准，我想，這是這些場景的一部分嗎？這是你從 FDA 聽到的嗎？或者這只是為所有的可能性做準備？

So a couple of things. Yes, there are essentially 2 issues at the agency at the same time. One is modifying the label to expand the label and to provide access to a much broader population of patients and as we said that there's repeating -- our BLA supplements requested the removal of all Asian ambulation related restrictions from the label because we believe that's founded on science. And of course, the second question then is this -- the view that we have satisfied the requirements for our confirmatory trial and the entire approval should be translated from accelerated to a traditional approval.

有幾件事。是的，該機構基本上同時存在兩個問題。一是修改標籤以擴大標籤範圍並為更廣泛的患者群體提供機會，正如我們所說的那樣，我們的 BLA 補充劑要求從標籤中刪除所有與亞洲行走相關的限制，因為我們相信這是基於科學。當然，第二個問題是，我們認為我們已經滿足了驗證性試驗的要求，整個批准應該從加速批准轉變為傳統批准。

There are many different scenarios there. There's obviously going to be dialogue about the breadth of the label? And then, of course, there'll be the dialogue about what portions of that are confirmed for traditional approval and what portions of that are confirmed for -- will remain an accelerated approval. So there are many iterations. We have a strong view on what we think the science justifies. So first, from an administrative perspective, the time lines are identical. So we have a June 21 target completion date that is for both of those issues. So we'll address both of those issues with June 21.

那裡有很多不同的場景。顯然會有關於標籤廣度的對話？然後，當然，將會就哪些部分被確認為傳統批准以及哪些部分被確認為加速批准進行對話。所以有很多迭代。我們對我們認為科學合理的觀點有強烈的看法。首先，從管理角度來看，時間軸是相同的。因此，我們將這兩個問題的目標完成日期定為 6 月 21 日。因此，我們將在 6 月 21 日解決這兩個問題。

And we're very pleased with June 21, as you know, because we had been guiding people to end of August from that perspective. On the substantive issues or what's going to happen in the review. That's going to be subject to the review and we're in the early days. Again, I'd say we're very pleased at least with the engagement of the division thus far, but we have more work to do and more discussions to be had and I don't want to overpromise before the end of this. I will also say there are a lot of different iterations from our perspective. Priority #1 is the broadest possible label.

如你所知，我們對 6 月 21 日感到非常滿意，因為我們一直從這個角度引導人們到 8 月底。關於審查中的實質問題或將要發生的事情。這將需要接受審查，而我們還處於早期階段。再說一遍，我想說，至少我們對該部門迄今為止的參與感到非常滿意，但我們還有更多的工作要做，需要進行更多的討論，我不想在此結束之前做出過多的承諾。我還要說，從我們的角度來看，有很多不同的迭代。優先級#1 是最廣泛的標籤。

So as between the 2 issues that we're discussing, we are first and foremost focused on the broadest possible label, given the potential of access and hopefully a better life the greatest number of patients. And then, of course, we also -- it's important to us, but the secondary issue is translating this from accelerated to traditional and the breadth of that will be a separate discussion. But we have more work to do and more discussions and work to do with the agency and June 21 will be our return date on all of that.

因此，在我們正在討論的兩個問題之間，我們首先關注的是盡可能廣泛的標籤，考慮到獲得最大數量患者的潛力並希望獲得更好的生活。當然，我們也——這對我們很重要，但次要問題是將其從加速轉化為傳統，其廣度將是一個單獨的討論。但我們還有更多的工作要做，還有更多的討論和工作需要與該機構進行，6 月 21 日將是我們對所有這些工作的返回日期。

Our next question comes from the line of Kostas Biliouris BMO Capital Markets.

我們的下一個問題來自 BMO Capital Markets 的 Kostas Biliouris。

Congrats on the impressive progress. So one quick question from us. If we assume that your label will expect ELEVIDYS used to ambulatory patients only for all ages, how straightforward would it be for physicians and importantly, payers to clearly determine whether someone is ambulatory or not, given that patients are losing ambulation progressively -- so there may be a state where the ambulation status is unclear. So would it be clear for physicians and payers to determine if someone is eligible or not?

祝賀取得了令人矚目的進展。我們提出一個簡短的問題。如果我們假設您的標籤期望ELEVIDYS 僅用於所有年齡段的可臥床患者，那麼考慮到患者逐漸失去臥床功能，對於醫生和重要的是付款人來說，清楚地確定某人是否可以臥床是多麼簡單- 所以有可能是行走狀態不清楚的狀態。那麼醫生和付款人可以清楚地確定某人是否符合資格嗎？

Okay. Thank you very much for your question. First, let me be clear. I resist the assumption that we've been able to get ambulatory alone, of course, because we are, at this point, seeking the removal of the ambulatory restrictions. But to your point, ambulation is in the label today. And the question then is what is -- how do the physicians determine what ambulation means? The short answer is that, that is left to the medical judgment of physicians, but there is good guidance in medical practice for that. It is based on functional assessments and functional tests. There are well-defined approaches. Probably the most common perhaps the most gold standard approach is the definition from synergy, which is that there is a patient reported continuous use of a wheelchair without ambulation. And then that is verified by the physicians, by the inability of the patient to walk meters unassisted. So that would be a typical functional assessment that a physician would use to determine ambulatory status. So this isn't an enormously difficult functional assessment and conclusion to make by physicians.

好的。非常感謝您的提問。首先，我要先明確一點。當然，我反對這樣的假設：我們已經能夠獨自走動，因為我們目前正在尋求取消走動限制。但就您而言，「步行」已經成為當今的標籤。接下來的問題是──醫生如何確定行走的意義？簡而言之，這取決於醫生的醫學判斷，但醫療實踐對此有很好的指導。它基於功能評估和功能測試。有明確定義的方法。最常見的也許是最黃金標準的方法可能是協同作用的定義，即有一名患者報告連續使用輪椅而不走動。然後，醫生透過患者無法在無人幫助的情況下行走數公尺來驗證這一點。因此，這將是醫生用來確定動態狀態的典型功能評估。因此，這對醫生來說並不是一個非常困難的功能評估和結論。

Our next question comes from the line of Neena Bitritto-Garg with Deutsche Bank.

我們的下一個問題來自德意志銀行的 Neena Bitritto-Garg。

Just a follow-up on the last question. Can you just remind us what data was included in the filing on patients with -- that are nonambulatory, if any, just to kind of clarify that.

只是最後一個問題的後續。您能否提醒我們，有關無法行走的患者的文件中包含了哪些數據（如果有的話），只是為了澄清這一點。

Yes. We had data from children up to 20 years old from a separate study that we call study 103 that went in with it. We obviously also have an ongoing study ENVISION, which is a study for non-ambulatory patients. Now that is an ongoing placebo-controlled trial, but the safety from that study is obviously made available to the FDA on a continuous basis. And all of that supports our BLA supplement.

是的。我們從一項單獨的研究（我們稱之為研究 103）中獲得了 20 歲以下兒童的數據。顯然，我們還有一項正在進行的研究 ENVISION，這是一項針對非臥床病患的研究。現在這是一項正在進行的安慰劑對照試驗，但研究的安全性顯然會持續向 FDA 提供。所有這些都支持我們的 BLA 補充。

Our next question comes from the line of Tim Lugo with William Blair.

我們的下一個問題來自蒂姆·盧戈和威廉·布萊爾的對話。

Can you discuss the level of warehousing currently occurring in the DMD community and maybe any subpopulations that are ahead of this potential expansion in the summer, which we should be aware of. I know we all focus on ambulatory and age related. Is there anything else there that we should be also looking maybe lung function or other subpopulations?

您能否討論一下 DMD 社區目前的倉儲水平，以及可能在夏季潛在擴張之前的任何亞群體，我們應該注意這一點。我知道我們都關注動態和年齡相關的問題。還有什麼我們還應該關注的可能是肺功能或其他亞群嗎？

Well, I don't -- I'm not 100% sure what we mean by warehousing to be honest. There is going to be an exceptional amount of demand for this therapy when the label is expanded both from the physician community but from families with Duchenne muscular dystrophy, and we stand prepared to build the material and have lots available to fully serve that demand over the course of 2024. But Dallan, do you have other thoughts on the warehousing question itself?

嗯，我不知道——說實話，我並不能 100% 確定我們所說的倉儲是什麼意思。當醫生群體和杜氏肌肉營養不良症家庭的標籤擴大時，對這種療法的需求將會非常大，我們隨時準備構建材料，並有大量可用材料來充分滿足這一需求2024 年的課程。但是Dallan ，您對倉儲問題本身還有其他想法嗎？

Yes. If it's related to the PMOs and warehousing with the PMOs in anticipation of the gene therapy we were worried about that leading up to the initial launch, and the team did an exceptional job of making sure that, that did not happen. And we don't -- we don't see widespread warehousing where patients are getting delayed or really any warehousing where people are foregoing PMO in anticipation of the gene therapy. So I think, as I mentioned in the script, we were -- one of the things we're particularly pleased with this year is the continued incredibly excellent execution of the PMO team for patients who were not eligible for the gene therapy for ELEVIDYS.

是的。如果這與基因療法預期的 PMO 和 PMO 的倉儲有關，我們在最初啟動之前就擔心這一點，而團隊做了出色的工作，確保這種情況不會發生。我們沒有看到患者被延誤的廣泛倉儲，也沒有看到人們因預期基因治療而放棄 PMO 的任何倉儲。因此，我認為，正如我在劇本中提到的，今年我們特別滿意的一件事是 PMO 團隊為不符合 ELEVIDYS 基因治療資格的患者持續提供令人難以置信的出色執行力。

Our next question comes from the line of Uy Ear with Mizuho.

我們的下一個問題來自Uy Ear 和Mizuho 的線路。

So just going back to the exon skipping products, could you -- I'm not asking full guidance or anything to that effect. Maybe just help us understand the first half of the year. In the prior quarter, growth -- year-over-year growth was relatively strong in the first half. Just wondering how we should sort of think about the first half of 2024 for those 3 products.

那麼，回到外顯子跳躍產品，我並不是要求完整的指導或任何類似的東西。也許只是幫助我們了解上半年。上一季的成長－上半年的年成長相對強勁。只是想知道我們應該如何看待這 3 種產品的 2024 年上半年。

We haven't provided guidance on the PMOs for this year, but we're doing very well. I think you saw very good performance on all 3 of the PMOs last year, in fact, AMONDYS and VYONDYS, we're still growing at double digits. And one of the things that's interesting is that we are not seeing right now and probably won't see a significant amount of cannibalization from ELEVIDYS. Over the course of 2024 that will have a significant impact on the P&L. So we feel very good about where we are with our RNA-based therapies in 2024.

我們還沒有提供今年專案管理辦公室的指導，但我們做得很好。我認為去年所有 3 位 PMO 的表現都非常好，事實上，AMONDYS 和 VYONDYS，我們仍在以兩位數的速度成長。有趣的事情之一是我們現在還沒有看到，也可能不會看到 ELEVIDYS 的大量蠶食。 2024 年，這將對損益產生重大影響。因此，我們對 2024 年基於 RNA 的療法的進展感到非常滿意。

Our next question comes from the line of Salveen Richter with Goldman Sachs.

我們的下一個問題來自 Salveen Richter 與高盛的對話。

This is Lydia on for Salveen. So if the label for ELEVIDYS is expanded and the broader population opens up, how do you think that physicians might prioritize which patients to treat first in the context of site constraints?

這是薩爾文的莉迪亞。因此，如果 ELEVIDYS 的標籤擴大並且開放更廣泛的人群，您認為醫生如何在場地限制的情況下優先考慮首先治療哪些患者？

Yes. That will be an issue that physicians are going to have to grapple with -- there are a number of constraints. One of the things that you have to recall or remember is that we need to ensure that we are always prioritizing great outcomes and safety over, for instance, short-term revenue. So we need to make sure that physicians -- and physicians will know this, and they're going to certainly consider this. They need to make sure that they can not only infuse patients but follow up appropriately. And so that will likely require them to prioritize patients as they consider this therapy.

是的。這將是醫生必須解決的問題——存在許多限制。您必須回憶或記住的一件事是，我們需要確保我們始終優先考慮偉大的成果和安全，例如短期收入。因此，我們需要確保醫生知道這一點，並且他們肯定會考慮這一點。他們需要確保不僅能夠為患者輸液，而且能夠適當地進行追蹤。因此，這可能需要他們在考慮這種療法時優先考慮患者。

The short answer is that we are -- we can't invade the practice of medicine and decide for them what to do. There is a compelling arguments on both across the spectrum. On the one hand, there may very well be physicians who want to prioritize very young children to get in and intervene before damage is done. On the other hand, for the nonambulatory patients and later patients, there is a race against time for those patients. And so getting to those patients and stopping damage before it's too late is extraordinarily important. So these are going to be difficult decisions physicians are going to have to work that out, and I'm sure there'll be white papers and discussions among thought leaders on that topic.

簡而言之，我們不能侵入醫學實踐並為他們決定該怎麼做。在整個範圍內，兩者都有令人信服的論點。一方面，很可能有些醫生希望優先考慮年幼的兒童，以便在傷害造成之前介入。另一方面，對於不能行走的患者和後來的患者來說，這些患者需要與時間競賽。因此，在為時已晚之前到達這些患者並阻止傷害就顯得異常重要。因此，這些將是醫生必須解決的困難決定，我相信思想領袖將就該主題發佈白皮書和討論。

The issue today is a slightly different one. The prioritization today, given the label that we have is to ensure that we get kids on the label, and this really comes from the physician more than from us to get kids on the label before they age out and the therapy won't be available to them. So if you look at the bias here, the bias tends to be to the -- in this tight age range of 4 and 5 to be in the later ages because they're really trying to get to those kids who, if they don't get through the administrative process, will age out to 6 years old.

今天的問題略有不同。考慮到我們所擁有的標籤，今天的首要任務是確保我們讓孩子進入標籤，這實際上更多地來自於醫生，而不是我們，目的是在孩子們變老、治療無法使用之前讓他們進入標籤。給他們。因此，如果你看看這裡的偏見，你會發現，在4 歲和5 歲這個狹窄的年齡範圍內，偏見往往是在較晚的年齡段，因為他們真的想接觸那些如果不這樣做的孩子.未通過行政程序，將減齡至6歲。

The good news is that if we can expand this label that issue goes to the side, and then we'll have to deal with the other issues about prioritization and the like. But it ultimately will be a physician decision and the issue of the practice of medicine for physicians.

好消息是，如果我們可以擴展這個標籤，那麼這個問題就可以放在一邊，然後我們將不得不處理有關優先順序等的其他問題。但這最終將是醫生的決定以及醫生的醫學實踐問題。

Our next question comes from the line of Ritu Baral with TD Cowen.

我們的下一個問題來自 Ritu Baral 和 TD Cowen 的對話。

I want to just to follow up on the sort of guidance given. Your comment on how not to expect additional growth in ELEVIDYS through the first half of the year, at least until the PDUFA, is that a comment or a reflection on just the fact that you've reached sort of a run rate on 4- to 5-year-old or is that a comment on sort of capacity of the systems throughput? Are you getting through as many patients as possible? And can you comment on what that sort of throughput capacity of like the center is at this point for when hopefully the label expands.

我只想跟進所提供的指導。您對如何在今年上半年（至少在 PDUFA 之前）預計 ELEVIDYS 不會出現額外增長的評論是對您已經達到 4 至 4 的運行率這一事實的評論或反思。5 歲了 還是這是對系統吞吐量的評論？您是否接待了盡可能多的患者？您能否評論一下，當希望標籤擴展時，中心的吞吐量是多少？

Yes, this really isn't a capacity issue right now. So I think as Dallan commented in his opening remarks, the label that we have today in this population, it's really a fairly unique population. First, as we all know, it's a very narrow age range, 4 to 5 years old. But that alone doesn't really describe the unique nature of this population because beyond that, there is a significant percentage of those patients that are not yet diagnosed. And so that makes it unusual. And then when they are diagnosed.

是的，現在這確實不是容量問題。因此，我認為正如達倫在開場白中評論的那樣，我們今天在這個人群中所貼上的標籤，這確實是一個相當獨特的人群。首先，眾所周知，它的年齡範圍非常窄，4到5歲。但僅憑這一點並不能真正描述該族群的獨特性質，因為除此之外，還有很大一部分患者尚未得到診斷。這使得它變得不尋常。然後當他們被診斷出來時。

Remember, they're not all getting diagnosed on 4 years in 1 day. Some of these kids are getting diagnosed deep into their 5s. And so what does that mean? It means that the family is faced with what is very likely the most devastating piece of news so far in their life, has to come to grips with that news, then understand it well enough and then go through the administrative process that exists to get approval, to get antibody tests to get an infusion data -- to get infused. So this is a really unique population.

請記住，他們並非全部在 4 年內 1 天就被診斷出來。其中一些孩子在五歲時就被診斷出患有這種疾病。那麼這意味著什麼呢？這意味著這個家庭面臨著他們一生中迄今為止最具毀滅性的消息，必須認真對待這個消息，然後充分理解它，然後通過現有的行政程序以獲得批准，進行抗體測試以獲得輸液數據——進行輸液。所以這是一個非常獨特的人群。

In light of that, just to give a shout out to the team, it is particularly impressive when one considers that we did $200 million in that product revenue this year. So what Dallan is really talking about when we talk about this is just simply that as we work through the prevalent population, this is a really unique population and much narrower than you might imagine, the 4 to 5.

有鑑於此，僅是向我們的團隊致敬，考慮到我們今年該產品的收入達到了 2 億美元，這一點尤其令人印象深刻。因此，當我們談論這個問題時，Dallan 真正談論的只是簡單地說，當我們研究流行人群時，這是一個非常獨特的人群，而且比您想像的要窄得多，即 4 到 5 個人群。

And so by the middle of this year, assuming the label expansion, you would get to a place where you begin to be treating the incident population as opposed to some -- a bolus prevalent population in this group. Now the good news is that we have a June 21 date for our request for a label expansion. So hopefully, by July, we'll have a broader label and we'll be able to serve a much greater percentage of the population.

因此，到今年年中，假設標籤範圍擴大，您將開始治療事件人群，而不是某些人群（該群體中的推注流行人群）。現在好消息是，我們提出標籤擴展請求的日期為 6 月 21 日。因此，希望到七月，我們將擁有更廣泛的標籤，並且能夠為更大比例的人口提供服務。

Our next question comes from the line of David Hoang with Citigroup.

我們的下一個問題來自花旗集團的 David Hoang。

I just wanted to ask a little bit more about the suspension culture manufacturing you have in the works. How fast did something like that come online? And once that is operationally how might that improve your margins?

我只是想多問一些關於你們正在進行的懸浮培養生產的情況。類似的東西上線的速度有多快？一旦投入運營，這將如何提高您的利潤？

So we're very excited about where we are from a suspension perspective. There's still a ton of more work to do, but a couple of things to think about. We are very advanced actually in the suspension work that we're doing, not just with 9001, but we're actually getting great results from a suspension perspective with our some of our limb-girdle programs. A couple of our sarcoglycan programs to actually transition to a suspension and we're making great progress there.

因此，從懸吊的角度來看，我們對我們所處的位置感到非常興奮。還有大量工作要做，但有幾件事需要考慮。事實上，我們在懸掛工作方面非常先進，不僅僅是 9001，而且從懸掛的角度來看，我們的一些肢帶項目實際上取得了很好的結果。我們的幾個肌聚醣計劃實際上已過渡到暫停狀態，我們正在這方面取得了巨大進展。

When we focus specifically on ELEVIDYS we are in engineering runs right now on suspension. We've done 500 liter. We're doing another 500 liter. We'll do -- will start in the next month or so, 2,000 liter. We're so far getting not only really tremendous enhancement on yield but really good product qualities.

當我們特別關注 ELEVIDYS 時，我們現在正在進行懸吊工程運行。我們已經做了500公升。我們還要再做 500 公升。我們會在下個月左右開始，2,000 公升。到目前為止，我們不僅在產量上取得了巨大的提高，而且產品品質也非常好。

If all goes well, our goal is to have this suspension process available commercially by 2026. Now that's a moonshot goal on our part with keeping the patients front and center. We're going to try to move as fast as possible. But hopefully, we have the history to prove that we can make -- we can come up with audacious plans and serve them. So we're really excited about that.

如果一切順利，我們的目標是在 2026 年之前將這種懸浮液工藝投入商業使用。現在，這是我們的一個宏偉目標，將患者放在首位。我們將嘗試盡可能快地行動。但希望我們有歷史證明我們可以製定大膽的計劃並為他們服務。所以我們對此感到非常興奮。

As far as what that might do, both from a capacity perspective as we go around the world with our partner, Roche, and a COGS perspective, that's going to require more work and more clarification as we get these runs done, but it won't be modest. It will be multiples. And we are seeing multiple times greater yields with suspension than we get with our iCELLis process, which as Ian mentioned, still drives right now an 80% margin.

就其可能的作用而言，無論是從我們與合作夥伴羅氏一起環遊世界的產能角度來看，還是從銷售成本角度來看，當我們完成這些運行時，都將需要更多的工作和更多的澄清，但它不會。不要謙虛。它將是倍數。我們發現，暫停後的產量比 iCELLis 製程的產量高出數倍，正如 Ian 所提到的，iCELLis 製程目前仍能帶來 80% 的利潤率。

So we're -- I mean you probably hear in my voice, a certain amount of enthusiasm for our manufacturing approach and our suspension approach. And this is -- it is still early days, and we're just in engineering runs right now, but we're very, very excited about what this could mean for our ability to bring this therapy across the world and at a lower cost of goods as we go across the world.

所以我們——我的意思是你可能從我的聲音中聽到了對我們的製造方法和懸吊方法的某種熱情。現在還處於早期階段，我們現在還處於工程運行階段，但我們非常非常興奮，這對於我們以較低的成本將這種療法推向世界的能力意味著什麼當我們穿越世界時的貨物。

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

我們的下一個問題來自邁克烏爾茲 (Mike Ulz) 與摩根士丹利 (Morgan Stanley) 的對話。

Maybe just a quick one on timing since the PDUFA date was granted 2 months ahead of expectations. Just curious if the thinking now is you'll probably get a decision close to the PDUFA date? Or is the FDA still really committed to rapidly reviewing and might get an answer sooner?

也許只是簡單介紹一下時間，因為 PDUFA 日期比預期提前了 2 個月。只是好奇您現在的想法是否可能會在接近 PDUFA 日期時做出決定？或者 FDA 是否仍然真正致力於快速審查並可能更快得到答案？

Well, I have no reason to believe that the FDA isn't committed to rapidly reviewing this. With that said, there's still a lot of work to be done, and I think it would be prudent for all of us to assume that our target completion date of June 21 as the date on which we're going to get the answer. We're prepped for June '21, even though we are -- I don't think anyone thinks we fiddle around, we try to move as fast as possible. But we're assuming June 21, that's when we're going to get our label expansion request answer.

好吧，我沒有理由相信 FDA 不致力於快速審查這一點。話雖如此，仍有許多工作要做，我認為我們所有人都應該謹慎地假設 6 月 21 日的目標完成日期是我們得到答案的日期。我們已經為 21 年 6 月做好了準備，儘管我們——我認為沒有人認為我們在閒逛，我們會盡力盡快採取行動。但我們假設 6 月 21 日將得到標籤擴展請求的答案。

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

我們的下一個問題來自丹妮爾·布里爾和雷蒙德·詹姆斯的對話。

This is Alex on for Danielle. I know the PMO confirmatory trials are fully enrolled. Could you just remind us whether -- where we should expect data for admission this year?

這是亞歷克斯為丹妮爾代言。我知道 PMO 確認性試驗已全部入組。您能否提醒我們，今年的入學數據該在哪裡？

No, we shouldn't -- it doesn't read out for 2026.

不，我們不應該——它沒有讀出 2026 年的數據。

Our next question comes from the line of Brian Skorney with Baird.

我們的下一個問題來自 Brian Skorney 和 Baird 的對話。

This is Charlie on for Brian. So we were just wondering if you've heard anything from Roche regarding time lines with the EMA as well as if the European opportunity were to come online, would there be any supply limitations resulting from that? I know you're very comfortable with the expansion of the label but bringing on a whole another content, do you think you have to do any prioritization between regions?

這是查理為布萊恩代言的。因此，我們只是想知道您是否從羅氏那裡聽說過有關 EMA 的時間表以及歐洲機會是否上線，是否會因此而產生任何供應限制？我知道您對品牌的擴展感到非常滿意，但是引入了全新的內容，您認為您必須在區域之間進行優先排序嗎？

Well, Roche is publicly saying that their goal is to submit in 2024. And then as it relates to supply, our supply plans include our partner, Roche.

那麼羅氏公開表示他們的目標是在2024年提交。然後說到供應，我們的供應計劃包括我們的合作夥伴羅氏。

And just one quick follow-up just to the previous question around mission and the timing. Just one thing to remind everyone is that this is a dose compared to doses of the drug. And so the data which we'll read out will be comparative from the 30 mg per kg compared to either the 100 mg or 200 mg per kg, and there's no risk of the drug being pulled off the market.

只是對上一個有關任務和時間安排的問題進行快速跟進。需要提醒大家的一件事是，這是與藥物劑量相比的劑量。因此，我們將讀出的數據將是 30 毫克每公斤與 100 毫克或 200 毫克每公斤的比較數據，並且不存在該藥物被撤出市場的風險。

Our next question comes from the line of Kristen Kaska with Cantor Fitzgerald.

我們的下一個問題來自克里斯汀·卡斯卡（Kristen Kaska）和坎托·菲茨杰拉德（Cantor Fitzgerald）的對話。

This is Rick Miller on for Kristen. Since launching, are you able to talk about if and how the profiles of DMD patients that you're looking to get on ELEVIDYS have changed? Or to put it in another way, I imagine you had highly engaged caregivers who are ready for ELEVIDYS on day 1. So are you seeing more patients coming forward now after a few months of commercial experience or caregivers to get their child in line for ELEVIDYS?

這是克里斯汀的里克·米勒。自推出以來，您能否談談您希望在 ELEVIDYS 上取得的 DMD 患者的資料是否以及如何改變？或者換句話說，我想您有高度敬業的護理人員，他們在第一天就準備好接受ELEVIDYS。因此，您是否看到更多的患者在經過幾個月的商業經驗後主動前來，或者護理人員讓他們的孩子排隊接受ELEVIDYS ？

Yes. I would say in the broadest of strokes, there is going to be a substantial demand for this therapy. I don't think that's changed. I think it's what we anticipated before launch, I don't think it's changed after launch. Duchenne muscular dystrophy is a devastating disease and the opportunity that's offered by ELEVIDYS is an important one. I think physicians understand that families with Duchenne muscular dystrophy, boys understand that as well. But Dallan, if you have any additional color on this or views, please share them.

是的。我想說，從最廣泛的角度來看，這種療法的需求將會很大。我認為這沒有改變。我認為這是我們在發布前的預期，我認為發布後沒有改變。杜氏肌肉營養不良症是一種毀滅性的疾病，ELEVIDYS 提供的機會非常重要。我認為醫生了解患有杜氏肌肉營養不良症的家庭，男孩也了解這一點。但是 Dallan，如果您對此有任何其他看法或觀點，請分享。

No, I think broadly speaking here, exactly right, Doug. It's -- we're not seeing a real a real major change in terms of the patients coming in. It is as we set up on a small population. And so as soon as they're getting diagnosed and they've had their discussions with the docs, they're coming in through the enrollment forms. And so we're just working through those patients as fast as they can -- as we can prior to them aging out. But no major differences in -- for example, there wasn't a big kind of bolus of patients that initially came in, and now that's different. It's just -- it's been a steady clip essentially.

不，我認為從廣義上講，完全正確，道格。這是——我們沒有看到患者進來方面發生真正的重大變化。這是因為我們在一小部分人群中建立了這一點。因此，一旦他們被診斷出來並與醫生進行了討論，他們就會填寫登記表。因此，我們只是盡可能快地治療這些患者——在他們衰老之前我們就可以做到。但沒有什麼重大差異——例如，最初進來的病人並沒有大量，但現在情況不同了。這本質上是一個穩定的剪輯。

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

我們的下一個問題來自 Anupam Rama 與摩根大通的對話。

At the conference in January, you talked about 70 sites being active and about half of those sites had dosed patients. Can you give us a sense of where you are kind of now in the first couple of months of the year?

在 1 月的會議上，您提到有 70 個站點處於活動狀態，其中大約一半的站點已對患者進行了給藥。您能為我們介紹一下您在今年頭幾個月的情況嗎？

Yes. I believe that, that remains the accurate answer. But Dallan, you can give us an update if there's any change in that?

是的。我相信，這仍然是準確的答案。但是 Dallan，如果有任何變化，你可以給我們更新嗎？

No, Anupam, that really hasn't changed all that much. There's obviously more than there was then. And there's a higher proportion of sites that have dosed. But we're actively looking at this on a daily basis, and we have this flexible model where we can bring on new sites, get them trained and up and ready as needed. So we've got more than enough sites up and running, and we threw out -- we've got great geographic coverage, but the team is also ready to support and serve as needed out there.

不，阿努帕姆，這確實沒有太大改變。顯然比當時多了。並且已經使用劑量的站點比例更高。但我們每天都在積極關注這個問題，並且我們擁有這種靈活的模式，我們可以在其中引入新站點，對它們進行培訓，並根據需要做好準備。因此，我們已經建立並運行了足夠的站點，但我們放棄了——我們擁有很大的地理覆蓋範圍，但團隊也準備好根據需要提供支援和服務。

I really do want to give kudos to this team for where we are. The -- I think everybody knows, the goal was to try to get to 50, not just 50 sites in 2024 -- 2023, by the end of 2023, which would have been record smashing for a gene therapy launch and that there was going to be this aspiration that maybe someday we could get to 70 sites that would be trained and up and running. And this team got, as you know, over 70 sites in 2023. But also the way they got there is something that gives me an enormous amount of pride, which is, as I said earlier in this call, we don't we don't prioritize revenue over patient safety and great outcomes far more important for us to ensure great outcomes.

我真的很想為這支球隊的現狀表示讚揚。我想每個人都知道，目標是在 2024 年、2023 年、2023 年底之前達到 50 個，而不僅僅是 50 個站點，這對於基因治療的推出來說將是創紀錄的，並且將會有為了實現這一願望，也許有一天我們可以讓70 個站點接受培訓並啟動並運行。如您所知，這個團隊在 2023 年獲得了 70 多個網站。而且他們獲得這些網站的方式也讓我感到非常自豪，正如我之前在電話會議中所說，我們不這樣做不要將收入置於在患者安全和良好結果之上，這對我們確保良好結果更為重要。

And this team has done a ton in that direction. These 70 sites that are activated or activated because they've all been well trained. They're in good shape to be able to safely infuse this therapy and get good outcomes and consistent outcomes which is important. We have a very laudable safety profile for full-body infusion gene therapy, and we want to ensure that remains the case over the long term, not in the short term.

這個團隊在這個方向上做了很多工作。這70個站點之所以被激活或被激活，是因為它們都經過了良好的訓練。他們狀態良好，能夠安全地註入這種療法並獲得良好的結果和一致的結果，這一點很重要。我們對於全身輸注基因療法的安全性非常值得稱讚，我們希望確保長期而不是短期內保持這種情況。

And then, of course, there's a lot of other programs around that, the ability to access experts so that every physician has an opportunity to get the right kind of information to inform the way they not only infuse but monitor patients and react to something that has been -- that is unique. I'm not sure anyone else has ever done the kind of work we've done. So we're in great shape right now to serve this community and serve it responsibly. So I'm really proud of where the team is right now. I think -- and frankly, it also explains our revenue in 2023.

當然，圍繞此還有很多其他計劃，能夠接觸專家，以便每個醫生都有機會獲得正確的信息，以告知他們不僅輸注而且監測患者並對某些情況做出反應的方式。一直以來——這是獨一無二的。我不確定是否有其他人做過我們所做過的工作。因此，我們現在處於良好的狀態，可以為這個社區提供服務，並負責任地為它服務。所以我對團隊現在的處境感到非常自豪。我認為——坦白說，這也解釋了我們 2023 年的收入。

Thanks, Doug. And as you were speaking, that team did get us just a direct answer to Anupam's question, and we're closing in on 60% of the sites have dosed. So it's just exactly as you said, it's just increasing as we go.

謝謝，道格。正如您所說，該團隊確實為我們提供了 Anupam 問題的直接答案，而且我們正在接近 60% 的網站已關閉。所以正如你所說，它只是隨著我們的進展而增加。

Thank you. I'd now like to turn the call back over to Doug Ingram for closing remarks.

謝謝。現在我想將電話轉回給道格·英格拉姆（Doug Ingram）做總結發言。

Thank you, Shannon. Thank you all for joining us today, and thank you for your insightful questions. We appreciate it. At the risk of repeating myself, I think 2023 was an extraordinarily important year for Sarepta. We -- a lot of folks on this team in concert with the patient community and investigators and physicians, frankly, moved heaven and earth get us where we are today. which is, I think, a fast-maturing fully integrated biotech organization committed to bringing a better life to patients with Duchenne muscular dystrophy, limb-girdles and other serious rare diseases.

謝謝你，香農。感謝大家今天加入我們，並感謝你們提出富有洞察力的問題。我們很感激。冒著重複自己的風險，我認為 2023 年對 Sarepta 來說是極其重要的一年。坦白說，我們這個團隊中的許多人與患者社群、研究人員和醫生合作，付出了天翻地覆的努力，才取得了今天的成就。我認為，這是一個快速成熟的完全整合的生物技術組織，致力於為杜氏肌肉營養不良症、肢帶和其他嚴重罕見疾病患者帶來更好的生活。

2024 is actually going to be even more significant if we are successful. And that's going to put us in a position where we can do a lot of good for a lot of rare disease patients and where we can reward those who have stuck with us and invested in a better life for these patients.

如果我們成功的話，2024 年實際上將會更加重要。這將使我們能夠為許多罕見疾病患者做很多好事，並獎勵那些堅持我們並為這些患者更好的生活而投資的人。

So I will remind you, if we are successful this year, and we brought in the label for ELEVIDYS and we can meet our goals this year, we are going to leverage our acumen and our financial strength and the talent of this team. And through both advancing our internal pipeline, but looking to external innovation, we will have the goal of growing even after ELEVIDYS not incrementally but in multiples. So we're going to build for ourselves a very big ambition if we are successful in 2024.

因此，我要提醒您，如果我們今年取得成功，引入 ELEVIDYS 品牌，並且能夠實現今年的目標，我們將利用我們的智慧、財務實力以及這個團隊的才能。透過推進我們的內部管道，同時尋求外部創新，我們的目標是即使在 EL​​EVIDYS 之後也能實現成長，不是增量而是倍數成長。因此，如果我們在 2024 年取得成功，我們將為自己建立一個非常遠大的抱負。

With that said, we need to focus on 2024 and be successful and the team is prepared to do that. And I look forward to updating you along the way as well. So thank you, and have a lovely evening.

話雖如此，我們需要專注於 2024 年並取得成功，團隊已準備好做到這一點。我也期待向您通報最新情況。謝謝您，祝您有個愉快的夜晚。

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

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。