Scholar Rock Holding Corp (SRRK) 2025 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to Scholar Rock's first-quarter financial results and business update call. (Operator Instructions)

女士們、先生們，感謝你們的支持，歡迎參加 Scholar Rock 第一季財務業績和業務更新電話會議。（操作員指示）

Please be advised that today's conference is being recorded. I would like now to turn the conference over to Scholar Rock.

請注意，今天的會議正在錄音。現在我想將會議交給 Scholar Rock。

Good morning. I'm Rushmie Nofsinger, Vice President of Corporate Affairs and Investor Relations at Scholar Rock. With me today are David Hallal, Chief Executive Officer; Akshay Vaishnaw, President of R&D; Keith Woods, Chief Operating Officer; and Vikas Sinha, Chief Financial Officer.

早安.我是 Scholar Rock 公司事務和投資者關係副總裁 Rushmie Nofsinger。今天與我一起的有執行長 David Hallal、研發總裁 Akshay Vaishnaw、營運長 Keith Woods 和財務長 Vikas Sinha。

For those of you participating via conference call, the accompanying slides can be accessed by going to the Events section of the Investors page on our website. During today's call, as outlined on slide 2, David will provide introductory remarks and provide a general business update, Akshay will review our clinical and regulatory progress, Keith will provide an update on our commercial readiness activities and Vikas will provide commentary on our company financials and a summary of our 2025 priorities. And then we will open the call for questions.

對於透過電話會議參與的各位，可以透過造訪我們網站「投資者」頁面的「活動」部分來存取隨附的幻燈片。在今天的電話會議中，如幻燈片 2 所述，David 將提供介紹性發言並提供一般業務更新，Akshay 將回顧我們的臨床和監管進展，Keith 將提供有關我們商業準備活動的最新信息，Vikas 將對我們公司的財務狀況進行評論並總結我們的 2025 年優先事項。然後我們將開始提問。

Before we begin, I'd like to remind you that during this call, we will be making various statements about Scholar Rock's expectations, plans and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. I encourage you to go to the Investors and Media section of our website for our most up-to-date SEC statements and filings.

在我們開始之前，我想提醒您，在本次電話會議中，我們將對 Scholar Rock 的期望、計劃和前景做出各種聲明，這些聲明構成了 1995 年《私人證券訴訟改革法案》安全港條款中的前瞻性聲明。任何前瞻性陳述僅代表我們截至今天的觀點，不應被視為代表我們未來任何日期的觀點。我鼓勵您造訪我們網站的「投資者和媒體」部分，以獲取我們最新的 SEC 聲明和文件。

With that, I'd like to turn the call over to David. David?

說完這些，我想把電話轉給大衛。戴維？

Thanks, Rushmie, and good morning. Thanks to everyone for joining us on today's call. 2025 is off to a strong start at Scholar Rock. In the first quarter, we made significant progress against our top priorities of bringing apitegromab to patients and families living with and suffering from SMA in the US, Europe and around the world.

謝謝，拉什米，早安。感謝大家參加今天的電話會議。 2025 年對 Scholar Rock 來說是一個好的開始。在第一季度，我們在將 apitegromab 帶給美國、歐洲和世界各地患有 SMA 的患者和家庭方面取得了重大進展。

We were very pleased with the positive Phase III SAPPHIRE trial, where we showed a statistically significant and clinically meaningful improvement in motor function as measured by the primary endpoint, the gold standard Hammersmith scale.

我們對第三階段 SAPPHIRE 試驗的正面結果感到非常滿意，根據主要終點——金標準 Hammersmith 量表的測量，我們發現運動功能有統計學上顯著且具有臨床意義的改善。

And in Q1, to underscore the body of evidence for apitegromab for patients with SMA, we were gratified that our BLA was granted priority review by the FDA with a September 22 PDUFA date. The team at Scholar Rock is working urgently to prepare for our US commercial launch, which will be the first country in a series of launches over the coming years.

在第一季度，為了強調 apitegromab 治療 SMA 患者的證據，我們很高興我們的 BLA 獲得了 FDA 的優先審查，PDUFA 日期為 9 月 22 日。Scholar Rock 團隊正在緊急籌備我們在美國的商業發布，美國將是未來幾年一系列發布中的第一個國家。

I am confident under Keith's leadership, we will assemble and deploy an experienced, talented and patient-centric team committed to the SMA community. Along with Keith, Akshay and Vikas, we now have the responsibility to bolster Scholar Rock's capabilities as we advance our mission to deliver apitegromab to patients with SMA.

我相信，在 Keith 的領導下，我們將組建和部署一支經驗豐富、才華橫溢、以患者為中心的團隊，致力於服務 SMA 社群。與 Keith、Akshay 和 Vikas 一起，我們現在有責任增強 Scholar Rock 的能力，同時推進我們的使命，為 SMA 患者提供 apitegromab。

This is what we know well and what we do well. We joined Scholar Rock at a time of great strength and opportunity as we scale for the next phase of growth to a commercial stage, fully integrated, global biopharmaceutical company. Globally, nearly 35,000 patients with SMA have received SMN-targeted therapies. And at Scholar Rock, we are working with urgency to prepare for our global launch, which we anticipate will commence in the US in Q3.

這是我們熟知的，也是我們擅長的。我們加入 Scholar Rock 正值我們實力雄厚、機會良多之際，我們正在為下一階段的成長做好準備，使其成為一家商業階段、完全整合的全球生物製藥公司。在全球範圍內，已有近 35,000 名 SMA 患者接受了針對 SMN 的治療。在 Scholar Rock，我們正在加緊準備我們的全球發布，預計將於第三季在美國開始。

We are also beginning to set the table to serve patients with SMA in Europe, Asia Pacific and Latin America. Our ambition at Scholar Rock is that any patient with SMA that can benefit from apitegromab should have access to apitegromab.

我們也開始為歐洲、亞太地區和拉丁美洲的 SMA 患者提供服務。Scholar Rock 的目標是讓任何能夠從 apitegromab 中受益的 SMA 患者都能獲得 apitegromab 治療。

I am confident that the global opportunity with apitegromab in SMA alone offers the potential for many years of sustainable growth that will power our company through the end of this decade and into the next. While we are very focused on our large opportunity to serve patients with SMA, we are continuing to evaluate expanding the study of apitegromab into other rare, severe and debilitating neuromuscular disorders. Akshay will touch upon this shortly.

我相信，apitegromab 僅在 SMA 領域帶來的全球機會就具有多年可持續成長的潛力，這將推動我們公司度過這個十年並邁入下一個十年。雖然我們非常重視為 SMA 患者提供服務的巨大機會，但我們仍在繼續評估將 apitegromab 的研究擴展到其他罕見、嚴重且使人衰弱的神經肌肉疾病。Akshay 很快就會談到這一點。

Now I'd like to turn to our exploratory cardiometabolic program, the EMBRAZE proof-of-concept study. Our effort here is to understand the role we may play in the treatment of obesity. We are the world leaders in myostatin biology and know well that GLP-1s have brought needed innovation to patients with obesity and cardiometabolic disorders.

現在我想談談我們的探索性心臟代謝計劃，即 EMBRAZE 概念驗證研究。我們在這裡的努力是了解我們在肥胖治療中可能扮演的角色。我們是肌肉生長抑制素生物學領域的世界領導者，並且深知 GLP-1 為肥胖和心臟代謝疾病患者帶來了所需的創新。

While the benefits outweigh the risks, muscle wasting and lean mass loss is something that the medical community is trying to address. The EMBRAZE study is our initial effort in the cardiometabolic space and will provide insights that will guide us moving forward.

雖然益處大於風險，但肌肉萎縮和瘦體重損失是醫學界正在努力解決的問題。EMBRAZE 研究是我們在心臟代謝領域的初步努力，將提供指導我們前進的見解。

We remain on track to share top-line results in June. Our achievements in 2025 to date underpin the opportunity before us to bring the potentially life-transforming benefits of apitegromab to patients and families with SMA.

我們仍將在六月公佈營收業績。我們在 2025 年迄今所取得的成就為我們帶來了將 apitegromab 的潛在改變生活的益處帶給 SMA 患者及其家庭的機會。

We are focused on delivering for patients with Akshay leading efforts in collaborating with US and EU regulators, Keith applying a similar approach from Vyvgart and MG to the commercial opportunity for apitegromab and Vikas focused on disciplined capital allocation to fuel near and long-term growth. With that, I'll turn the call over to Akshay to provide a more detailed update on our R&D progress.

我們專注於為患者提供服務，其中 Akshay 主導與美國和歐盟監管機構的合作，Keith 採用與 Vyvgart 和 MG 類似的方法為 apitegromab 尋找商業機會，而 Vikas 則專注於嚴格的資本配置，以推動短期和長期增長。說完這些，我將把電話轉給 Akshay，讓他提供有關我們研發進度的更詳細的更新。

Akshay?

阿克謝？

Thanks, David. I'm delighted to be here after six years on the Board of Scholar Rock. As a physician scientist, I could not be more excited to have seen the concept of apitegromab, our highly innovative anti-myostatin antibody, go from bench to bedside with our remarkable SAPPHIRE data. SAPPHIRE showed that apitegromab has the potential to reverse the progression of SMA from a loss of motor function to a gain of motor function. Specifically, the study demonstrated a statistically significant improvement in Hammersmith as patients on placebo worsened.

謝謝，大衛。在 Scholar Rock 董事會任職六年後，我很高興來到這裡。身為醫師科學家，我非常高興看到我們高度創新的抗肌生長抑制素抗體 apitegromab 的概念透過我們卓越的 SAPPHIRE 數據從實驗室走向臨床。SAPPHIRE 研究表明，apitegromab 具有逆轉 SMA 從運動功能喪失到運動功能恢復的潛力。具體來說，研究表明，服用安慰劑的患者病情惡化，而哈默史密斯的病情卻出現了統計上顯著的改善。

Importantly, patients treated with apitegromab had an approximately three-fold higher chance of a three-point or greater increase in Hammersmith versus those on placebo. Along with the very encouraging safety profile, the SAPPHIRE data suggests that apitegromab has great potential to provide clinically significant benefit to patients with SMA despite the use of background SMN-targeted therapies.

重要的是，與接受安慰劑治療的患者相比，接受 apitegromab 治療的患者 Hammersmith 評分增加三個點或更多的可能性大約高出三倍。除了非常令人鼓舞的安全性之外，SAPPHIRE 數據表明，儘管使用背景 SMN 標靶療法，apitegromab 仍具有為 SMA 患者提供臨床顯著益處的巨大潛力。

Additionally, at the Muscular Dystrophy Association Conference in Dallas in March, the detailed data from the SAPPHIRE trial were presented for the first time. These data demonstrated that treatment with apitegromab achieved clinically meaningful and consistent benefit in motor function across prespecified SMA patient subgroups, including the type of SMN-targeted therapy, age, age of initiation of SMN therapy and geography. Efficacy was also supported by additional analyses of outcome measures of motor function such as the revised upper limb module and the World Health Organization Motor Development Index.

此外，在三月於達拉斯舉行的肌肉萎縮症協會會議上，SAPPHIRE 試驗的詳細數據首次公佈。這些數據表明，apitegromab 治療在預先指定的 SMA 患者亞群中取得了具有臨床意義且一致的運動功能益處，包括 SMN 標靶治療的類型、年齡、開始 SMN 治療的年齡和地理位置。對運動功能結果測量的額外分析（例如修訂的上肢模組和世界衛生組織運動發育指數）也支持了療效。

As David mentioned, our BLA was accepted under priority review by the FDA and the MAA was validated by the EMA in Europe. Turning first to the FDA. We were gratified that our BLA for apitegromab was granted priority review by the agency with a September 22 PDUFA date.

正如 David 所提到的，我們的 BLA 已被 FDA 優先審查，MAA 也已獲得歐洲 EMA 的驗證。首先談談 FDA。我們很高興，我們的 apitegromab 生物製品許可申請 (BLA) 獲得了該機構的優先審查，PDUFA 日期為 9 月 22 日。

We feel the potential clinical benefits of apitegromab as demonstrated by our Phase III trial are underscored by the FDA's priority review designation. By definition, a priority review designation by the agency conveys the capacity of apitegromab to potentially impact unmet need in SMA by either being a treatment for a serious or life-threatening condition or provide a significant improvement in safety or effectiveness over existing treatments.

我們認為，FDA 的優先審查指定強調了我們的 III 期試驗所證明的 apitegromab 的潛在臨床益處。根據定義，該機構的優先審查指定表明 apitegromab 有能力透過治療嚴重或危及生命的疾病或提供比現有治療方法更顯著的安全性或有效性來影響 SMA 中未滿足的需求。

I'm excited that our team continues to work collaboratively with regulators and that we remain on track. With the success of SAPPHIRE, we're just beginning to tap into the broader potential of our truly innovative myostatin platform. There's much more we can do with the promise of apitegromab and our platform by delivering advances in severe neuromuscular diseases, including the muscular dystrophies such as DMD and FSHD.

我很高興我們的團隊繼續與監管機構合作，我們仍保持在正軌上。隨著 SAPPHIRE 的成功，我們才剛開始挖掘我們真正創新的肌肉生長抑制素平台的更廣泛潛力。利用 apitegromab 和我們的平台，我們可以做更多的事情，在嚴重神經肌肉疾病（包括 DMD 和 FSHD 等肌肉營養不良症）方面取得進展。

Additionally, we're advancing SRK-439, a highly innovative and potent subcu anti-myostatin antibody to the clinic. Based on preclinical data, SRK-439 has the potential to inhibit myostatin and increase muscle mass and creates options for our pipeline.

此外，我們正在將 SRK-439（一種高度創新且有效的皮下抗肌生長抑制素抗體）推向臨床。根據臨床前數據，SRK-439 具有抑制肌肉生長抑制素和增加肌肉質量的潛力，並為我們的產品線創造了選擇。

We remain on track to file the IND application for SRK-439 to support the first-in-human study in Q3. Now earlier, David mentioned the potential role Scholar Rock can play in addressing lean mass in cardiometabolic diseases. As we all appreciate, whilst GLP-1s offer quantitative benefits in terms of weight loss, much more needs to be done from a qualitative perspective regarding preserving lean mass. Notably, 1/4 to 1/3 of the weight loss with GLP-1s is due to the loss of muscle.

我們將繼續按計劃提交 SRK-439 的 IND 申請，以支持第三季的首次人體研究。之前，David 提到了 Scholar Rock 在解決心臟代謝疾病中的瘦體重方面可能發揮的作用。眾所周知，雖然 GLP-1 在減肥方面提供了定量的益處，但從維持瘦體重的品質角度來看，還需要做更多的工作。值得注意的是，GLP-1 導致的體重減輕的 1/4 到 1/3 是由於肌肉流失造成的。

Looking forward, it will be important to preserve muscle from the viewpoint of the associated metabolic benefits and a healthier approach to weight loss.

展望未來，從相關的代謝益處和更健康的減肥方法的角度來看，保持肌肉非常重要。

Our EMBRAZE study is our ongoing Phase II trial to investigate preliminarily the potential of further developing our highly selective anti-myostatin approaches in patients with obesity with the goal of reducing the loss of lean mass. We look forward to the upcoming readout of our initial data from EMBRAZE in June 2025.

我們的 EMBRAZE 研究是我們正在進行的 II 期試驗，旨在初步研究進一步開發我們針對肥胖患者的高度選擇性抗肌生長抑制素方法的潛力，目的是減少瘦體重的損失。我們期待 2025 年 6 月讀取 EMBRAZE 的初始資料。

In summary, we remain focused and on track to deliver on our key priorities this year. We will, one, drive the US approval of apitegromab in Q3 2025 and advance the EU court approval in 2026; two, initiate a study of apitegromab for infants and toddlers with SMA under the age of 2 starting in Q3; three, file an IND for SRK-439 in the third quarter; and finally, complete our clinical development plans for apitegromab in additional neuromuscular indications.

總而言之，我們將繼續集中精力並按計劃實現今年的重點任務。第一，我們將推動apitegromab在2025年第三季度獲得美國批准，並提前在2026年獲得歐盟法院的批准；第二，從第三季度開始對2歲以下SMA嬰幼兒開展apitegromab的研究；第三，在第三季度提交SRK-439的IND申請；最後，完成apitegromab在其他神經肌肉適應症中的臨床開發計劃。

With that, I'll turn it over to Keith to provide a commercial update. Keith?

有了這些，我將把它交給 Keith 來提供商業更新。基思？

Thanks, Akshay, and good morning, everyone. I'd first like to thank our colleagues from research and development for their focus and commitment over the years to make the September 22 PDUFA date for apitegromab a reality. SMA is a disease impacted by both motor neuron degeneration and muscle atrophy. Today's therapies only address one piece of the puzzle, the motor neurons. Currently, there are no approved muscle-targeted therapeutics to treat muscle atrophy.

謝謝，Akshay，大家早安。首先，我要感謝我們研發部門的同事們多年來的專注和承諾，讓 9 月 22 日 Apitegromab PDUFA 的日期成為現實。SMA 是一種受運動神經元變性和肌肉萎縮影響的疾病。現今的治療方法僅解決難題的一個部分，即運動神經元。目前，尚無核准的針對肌肉的療法來治療肌肉萎縮。

With apitegromab, we have the opportunity to usher in a new era for the treatment of patients with SMA. This is a progressive and devastating disease that leads to the loss of mobility, limited activities of daily living and a lack of independence. Despite the advances made in treating SMA with SMN-targeted therapies over the last decade, the contemporaneous natural history data shows that the majority of patients still experience progressive muscle degeneration over time.

有了apitegromab，我們有機會開創SMA患者治療的新時代。這是一種漸進性和毀滅性的疾病，會導致行動能力喪失、日常生活活動受限和缺乏獨立性。儘管過去十年利用 SMN 標靶療法治療 SMA 取得了進展，但同期的自然史數據表明，大多數患者仍然會隨著時間的推移經歷進行性肌肉退化。

The bottom line, nearly all patients and families living with SMA are demanding a transformative new therapy. This is supported by a Cure SMA survey published last month, where 90% of patients identified that new SMA treatment options improving muscle strength is an important need.

最重要的是，幾乎所有患有 SMA 的患者和家庭都要求一種變革性的新療法。上個月發布的《治癒 SMA》調查支持了這一點，其中 90% 的患者認為，提高肌肉力量的新型 SMA 治療方案是一項重要需求。

Our market research and interactions with healthcare professionals tell us that 80% of treating neurologists agree that preserving muscle should start as early as possible in treating patients living with SMA. Today, there are approximately 10,000 patients with SMA in the United States and roughly 2/3 of them have received an SMN-targeted therapy.

我們的市場調查和與醫療保健專業人士的互動告訴我們，80% 的治療神經科醫生同意，在治療 SMA 患者時應儘早開始保留肌肉。目前，美國約有 10,000 名 SMA 患者，其中約 2/3 接受了針對 SMN 的治療。

For these patients, as Akshay shared with our SAPPHIRE data, apitegromab showed the potential to reverse the progression of SMA from a loss of motor function to a gain of motor function. Furthermore, globally, there are approximately 35,000 individuals that have already received an SMN-targeted therapy. Neurologists recognize that in the future, a treatment approach of dual modalities to target the motor neuron and the muscle will be necessary to treat SMA.

對於這些患者，正如 Akshay 與我們的 SAPPHIRE 數據所分享的那樣，apitegromab 顯示出逆轉 SMA 從運動功能喪失到運動功能恢復的潛力。此外，全球約有 35,000 人已經接受了 SMN 標靶治療。神經科醫生認識到，未來治療 SMA 需要針對運動神經元和肌肉的雙重治療方法。

At Scholar Rock, we have the opportunity to make a meaningful difference for both children and adults living with SMA, first starting in the US, then Europe, Asia Pacific and Latin America. We are currently building on the momentum that has already been established for a successful US launch. Last weekend, several of us at Scholar Rock had the opportunity to meet with patients and their families at the Cure SMA Walk-n-Roll in Boston. We continue our stakeholder engagement and SMA disease education.

在 Scholar Rock，我們有機會為患有 SMA 的兒童和成人帶來有意義的改變，首先在美國，然後在歐洲、亞太和拉丁美洲。我們目前正在利用已經建立的勢頭，為成功在美國推出產品做準備。上週末，我們 Scholar Rock 的幾個人有機會在波士頓的 Cure SMA Walk-n-Roll 活動中與患者及其家人見面。我們將繼續與利害關係人進行合作並進行 SMA 疾病教育。

Life Takes Muscle is the first muscle-focused SMA disease awareness initiative. Our fully staffed US market access team is currently meeting with key US commercial and federal payers. Our process of hiring and onboarding our customer-facing team of roughly 50 sales, reimbursement and patient support personnel is well underway.

Life Takes Muscle 是第一個以肌肉為重點的 SMA 疾病宣傳倡議。我們人員齊備的美國市場准入團隊目前正在與美國主要商業和聯邦付款人會面。我們面對客戶的團隊由大約 50 名銷售、報銷和患者支援人員組成，招募和培訓工作正在順利進行中。

We expect to be fully staffed by mid-2025, well ahead of our potential launch in late September. Finally, we believe that apitegromab has the potential to be a first-in-class, best-in-class therapeutic to establish a new standard of care in SMA.

我們預計到 2025 年中期就能配備齊全部員工，比我們可能在 9 月底推出的產品早得多。最後，我們相信 apitegromab 有潛力成為一流的、最佳的治療方法，為 SMA 的治療樹立新的標準。

Now I will turn the call over to Vikas. Vikas?

現在我將把電話轉給維卡斯。維卡斯？

Thank you, Keith, and good morning, everyone. I'm pleased to provide our business update and provide insights into how we are thinking about resource allocation in the future. The opportunity with apitegromab in SMA alone offers the potential for many years of sustainable growth and will enable strategic, thoughtful investment in our pipeline to develop new indications and new therapies for an increasing number of patients. These pipeline investments will be aligned to our commercial success. We ended the quarter with $364.4 million.

謝謝你，基思，大家早安。我很高興提供我們的業務更新，並提供有關我們如何考慮未來資源分配的見解。光是 Apitegromab 在 SMA 領域的應用就提供了多年可持續成長的潛力，並將使我們能夠對產品線進行策略性、深思熟慮的投資，從而為越來越多的患者開發新的適應症和新的療法。這些管道投資將與我們的商業成功保持一致。本季結束時我們的營收為 3.644 億美元。

During the quarter, we continued to increase our investments in commercial readiness and inventory build-out. As we look ahead, we are prioritizing the commercial launch and ongoing clinical programs. We have an additional $100 million under our debt facility that we can draw down this year to support the upcoming launch, bringing our anticipated runway into 2027.

本季度，我們持續增加對商業準備和庫存建設的投資。展望未來，我們優先考慮商業發布和正在進行的臨床項目。我們的債務融資中還有額外的 1 億美元，我們可以在今年動用這筆資金來支持即將推出的產品，從而使我們的預期跑道能夠延伸到 2027 年。

We are working on building a tighter financial plan and we'll share more details over the next few quarters. As we move forward, I will focus first on driving strong performance with financial discipline; next, investing in capital-efficient commercial build-out; and thoughtful capital allocation to advance our pipeline.

我們正在製定更嚴格的財務計劃，並將在接下來的幾個季度分享更多細節。隨著我們不斷前進，我將首先致力於透過財務紀律推動強勁業績；其次，投資於資本高效的商業建設；並進行周到的資本配置，以推進我們的產品線。

With that, I will turn it back to David.

說完這些，我就把話題轉回給大衛。

Thanks, Vikas. In closing, we are acutely focused on the key priorities that will enable us to build and scale Scholar Rock into the next global biotech powerhouse. First, regulatory approvals and the upcoming U.S. launch of apitegromab for patients with SMA followed by a series of country launches in the coming years. Next, develop apitegromab for additional rare, severe and debilitating neuromuscular diseases.

謝謝，維卡斯。最後，我們高度重視那些能讓我們將 Scholar Rock 建設和擴展為下一個全球生物技術強國的關鍵優先事項。首先，apitegromab 將獲得監管部門的批准並在美國上市，用於治療 SMA 患者，隨後幾年將在一系列國家上市。接下來，開發 apitegromab 來治療其他罕見、嚴重和使人衰弱的神經肌肉疾病。

And finally, phase our capital allocation and investments thoughtfully to support our high-value commercial and development initiatives. On behalf of every member of the Scholar Rock team, we are deeply aware of our responsibility to patients and their families and will work with urgency to ensure that no patient with SMA is left behind. With that, we'll now open the line for questions.

最後，我們精心規劃資本配置和投資，以支持我們的高價值商業和發展計劃。我代表 Scholar Rock 團隊的每一位成員，深知我們對患者及其家人的責任，並將緊急努力確保不落下任何一位 SMA 患者。現在，我們將開放問答熱線。

Operator?

操作員？

(Operator Instructions) Allison Bratzel, Piper Sandler.

（操作員指示）Allison Bratzel、Piper Sandler。

Just two from me. Ahead of apitegromab launch, could you just frame for us how your discussions with US payers have gone? How receptive are they to coverage of combination therapy for both an SMN targeting and a muscle targeting therapy in SMA patients? And can you also describe that feedback for ex-US payers and governments as well?

我只差兩個。在 Apitegromab 上市之前，您能否向我們介紹一下您與美國付款人的討論進度如何？他們對 SMA 患者 SMN 標靶治療和肌肉標靶治療的聯合治療的接受程度如何？您能否也描述一下美國以外付款人和政府的回饋？

And then second, could you just characterize interactions with FDA on the apitegromab review? Obviously, there's a lot of concern about the state of the agency right now. So just want to know if you're -- if you have anything to report on there?

其次，您能否描述一下與 FDA 在 apitegromab 審查中的互動？顯然，目前人們對該機構的狀況非常擔憂。所以我只是想知道您是否有任何事情要報告？

Thanks, Ali. So why don't I just touch on pricing, then Keith will comment more specifically and then Akshay will take on the regulatory update question. One of the things that Keith and I have spent a long time sort of thinking about and sort of doing as it relates to, in general, really what we're talking about is access for a potentially transformative therapy for a small population of patients.

謝謝，阿里。那我為什麼不直接談定價呢，然後 Keith 會更具體地發表評論，然後 Akshay 會回答監管更新問題。基斯和我花了很長時間思考和做的事情之一就是，總的來說，我們真正談論的是讓一小部分患者獲得具有潛在變革意義的治療。

And we would sort of expect as we think about establishing access plans that we consider sort of pricing for our therapies that would be reflective of the rarity of the disease, the severity of the disease and the value that our therapy would provide to patients, in this specific case, patients with SMA. And I think one of the other things that Keith and I think a lot about is also given the rarity of disease.

當我們考慮制定獲取計劃時，我們會考慮我們的療法的定價，這將反映疾病的罕見性、疾病的嚴重程度以及我們的療法為患者（在這個特定情況下為 SMA 患者）提供的價值。我認為，我和基斯經常思考的另一件事也是考慮到疾病的罕見性。

We would expect that the budget impact to any one single payer in the US or even globally would be very limited for the high-value proposition. As it relates to sort of the engagement with payers largely in the US, I'll turn it over to Keith for some more commentary.

我們預計，對於美國乃至全球任何單一付款人來說，高價值主張的預算影響都將非常有限。由於這主要涉及與美國付款人的互動，因此我將把它交給 Keith 進行更多評論。

Thanks, David. So Ali, what we know in speaking with payers is that with SMN-targeted therapies alone, patients can still have progressive motor function loss. And at the MDA in Dallas in March, we heard that a proportion of patients are already receiving more than one SMN therapy, so SMN-targeted therapy.

謝謝，大衛。因此，阿里，我們在與付款人交談時了解到，僅採用 SMN 標靶療法，患者仍可能出現進行性運動功能喪失。在三月達拉斯的 MDA 上，我們聽說有一部分患者已經接受了不只一種 SMN 療法，也就是針對 SMN 的療法。

So right now, it's not uncommon that you'll see a payer pay for more than one of these therapies. As you know, with our data, when we go in addition to an SMN-targeted therapy, we see improvement consistent across all age groups of 2 to 21.

因此，現在你會看到付款人為多種療法付費的情況並不少見。如您所知，根據我們的數據，當我們結合 SMN 標靶治療時，我們發現 2 至 21 歲所有年齡層的患者病情都有持續改善。

And so with that in mind, these patients need a better therapeutic. And our early discussions with payers have proven to be positive and we'll continue those discussions. As for Europe, we plan to -- as you know, we filed and we're going through the regulatory process right now. We will be preparing to go into reimbursement discussions. Let's remember that we are going to sequence through Europe and we will start with Germany in 2026.

因此考慮到這一點，這些患者需要更好的治療方法。我們與付款人的早期討論已被證明是積極的，我們將繼續這些討論。至於歐洲，我們計劃——如你所知，我們已經提交了申請，目前正在進行監管程序。我們將準備進行報銷討論。讓我們記住，我們將按順序穿越歐洲，並將於 2026 年從德國開始。

And then we will roll out over time how we will sequence through the remainder of the countries in Europe. Thanks for the question.

然後，我們將逐步推出如何依序遍及歐洲其餘國家。謝謝你的提問。

And maybe a closer look at regulatory.

也許需要更仔細地研究監管。

Sure. Thanks, David. So thanks, Ali, for the question on FDA interactions. Look, it's a time of evolution and change at the FDA. We all recognize that.

當然。謝謝，大衛。所以，感謝 Ali 提出有關 FDA 交互作用的問題。瞧，這是 FDA 進化和變革的時期。我們都認識到這一點。

But what I'm delighted by is that the pace and the collaborative conversations we've had with the FDA are all going as per routine and we continue to guide that we're focused on working with the FDA and delivering on that September 22 PDUFA date.

但令我高興的是，我們與 FDA 的合作進度和對話都按常規進行，我們將繼續專注於與 FDA 合作並在 9 月 22 日的 PDUFA 日期之前完成任務。

So really, we're seeing no issues in specific to apitegromab and the SMA approval. And we're also delighted that FDA Commissioner, Martin Makary, actually made the point that with all the changes, one of the main areas of focus continues to be rare disease and delivering on what patients need for rare disease. So it's all systems go here and we continue to work productively with regulators here and in Europe.

因此，實際上，我們沒有發現 apitegromab 和 SMA 批准方面存在任何問題。我們也很高興 FDA 局長馬丁·馬卡里 (Martin Makary) 明確指出，儘管發生了所有這些變化，但主要關注領域之一仍然是罕見疾病以及滿足患者對罕見疾病的治療需求。因此，所有系統都正常運行，我們繼續與這裡和歐洲的監管機構進行富有成效的合作。

Michael Yee, Jefferies.

麥可‧餘 (Michael Yee)，傑富瑞集團 (Jefferies)。

Maybe just two questions on obesity coming up in June. Given that it's towards the end of the second quarter, but also that there's two different endpoints, I think, 24 and 32 weeks, are you thinking about providing more data to be a more complete package of information to help people out in terms of longer term follow-up data on some of the metabolic parameters that could come out in June? Have you thought about that?

也許六月只會提出兩個有關肥胖的問題。鑑於現在已經接近第二季末，而且有兩個不同的終點，我認為是 24 週和 32 週，您是否考慮提供更多數據以形成更完整的信息包，以幫助人們獲得可能在 6 月份公佈的一些代謝參數的長期跟踪數據？你有考慮過這個問題嗎？

And then just holistically, the prior CEO Jay has mentioned a 20% to 40% reduction in muscle loss would be great, but I think people are still sort of trying to grasp what you think a good result is and what is exciting. Can you give us some color on that?

從整體上看，前任執行長傑伊曾提到，減少 20% 到 40% 的肌肉損失會很棒，但我認為人們仍在試圖了解什麼是好的結果以及什麼是令人興奮的。您能給我們講講這個嗎？

Yes. Great questions, Mike. As Akshay and I noted, this is our first effort at really understanding what role we may be able to play in this space. We know that there is a need that the medical community is trying to address. And I'll turn it over to Akshay for sort of a closer look at what one might expect in terms of, as you were saying, the 24-week endpoint, but then the 8-week sort of withdrawal of the therapy as well. Akshay?

是的。很好的問題，麥克。正如 Akshay 和我所指出的，這是我們第一次真正嘗試了解我們能夠在這個領域發揮什麼作用。我們知道醫學界正在努力解決這項需求。我將把問題交給 Akshay，讓他更仔細地了解人們對您所說的 24 週終點以及隨後 8 週的治療停藥期可能有何預期。阿克謝？

Yes. Thanks, Mike. So the core of it, we'll be providing the 24-week data. That's the main study. We'll certainly provide any necessary follow-up information that we have that helps us understand and helps everybody else understand the potential of an anti-myostatin approach in the obesity space.

是的。謝謝，麥克。因此，其核心是我們將提供 24 週的數據。這是主要的研究。我們當然會提供任何必要的後續信息，以幫助我們了解並幫助其他人了解抗肌生長抑制素方法在肥胖領域的潛力。

We're excited to test this hypothesis preliminarily. It's an important one. I think we all appreciate that loss of muscle is almost certainly not a good thing as people lose weight, especially when it's 1/4 to 1/3 of the weight loss is due to muscle. And so the primary focus will be the 24-week data, change in lean mass, the safety and helping us understand the path forward. So I'll leave it at that, but it's not so long to wait until we get the data.

我們很高興能夠初步驗證這個假設。這是很重要的一點。我想我們都明白，當人們減肥時，肌肉的損失幾乎肯定不是一件好事，特別是當體重減輕的 1/4 到 1/3 是由於肌肉造成的時。因此，主要關注點將是 24 週的數據、瘦體重的變化、安全性以及幫助我們了解未來的道路。所以我就不多說了，但我們很快就能得到數據了。

Tess Romero, JPMorgan.

摩根大通的泰絲·羅梅羅。

So in the US, you noted collaboration with regulators and that you remain on track here. Can you confirm or not if you have completed your mid-cycle meeting? And if so, can you comment on any high-level discussions you have had around labeling? And at this time, what has the agency said about the need or lack thereof for an AdCom?

因此，在美國，您注意到與監管機構的合作，並且您在這裡仍然保持在正軌上。您能否確認您是否已完成中期會議？如果是的話，您能否評論一下有關標籤的任何高層討論？目前，該機構對於是否需要 AdCom 有何看法？

Thanks, Tess. As Akshay and I both noted in the call today, we remain on track. And maybe for a closer look on just kind of where we are, Akshay can provide a little bit more detail.

謝謝，苔絲。正如阿克沙伊和我今天在電話中提到的那樣，我們仍在按計劃進行。也許為了更深入地了解我們所處的位置，Akshay 可以提供更多細節。

Yes. I mean, there's not much more to provide other than the conversations have been extremely constructive and right on track, I would say. As to the details of when and how the various interactions occur, I don't really think this is a time or space. But I do want to reassure everybody that our ability today to guide on the call that we're heading to that September 22 PDUFA date is based on a series of very constructive conversations. So I'll leave it at that and more news as we get it.

是的。我的意思是，除了對話非常有建設性並且進展順利之外，沒有什麼可以提供的了。至於各種互動何時以及如何發生的細節，我並不真正認為這是一個時間或空間。但我確實想向大家保證，我們今天能夠在電話會議上指導我們即將迎來 9 月 22 日的 PDUFA 日期，這是基於一系列非常有建設性的對話。所以我先就此打住，等我們得到更多消息後再說。

David Nierengarten, Wedbush.

韋德布希的戴維‧尼倫加滕 (David Nierengarten)。

I just had one on the additional potential indications for apitegromab. As I recall, there's a lot of exploration in preclinical models, at least of DMD and related disorders. Is there any particular new development or new treatments that you think are particularly attractive to bring apitegromab forward into one of the other neuromuscular indications? And just kind of help us out with thinking about the expansion plans.

我剛剛了解到了 Apitegromab 的其他潛在適應症。我記得，在臨床前模型方面有很多探索，至少在 DMD 和相關疾病方面。您是否認為有特別有吸引力的新進展或新療法可以將 Apitegromab 應用於其他神經肌肉適應症？並幫助我們思考擴張計畫。

Thanks very much, David. Akshay?

非常感謝，大衛。阿克謝？

Yes. Thanks, David. So look, I think with apitegromab and our really unique and potent anti-myostatin platform, we have an incredible opportunity to not just help in SMA across the spectrum of disease there, but well beyond that into other neuromuscular disorders, which -- many of which are very severe and life-threatening. As you said, we've certainly spoken about and done a lot of good work on DMD and FSHD models, two very important muscular dystrophies. We've shared those data.

是的。謝謝，大衛。所以，我認為，有了 apitegromab 和我們真正獨特且強大的抗肌生長抑制素平台，我們就有了一個絕佳的機會，不僅可以幫助治療各種 SMA 疾病，還可以幫助治療其他神經肌肉疾病，其中許多疾病非常嚴重且危及生命。正如您所說，我們確實討論過 DMD 和 FSHD 模型（兩種非常重要的肌肉營養不良症），並且做了很多出色的工作。我們已經分享了這些數據。

People are very excited about them. And the fact that we've validated apitegromab as having the ability to put on the degree of muscle that it can in such a serious disease, SMA obviously bodes well in these other neuromuscular disorders. There are other indications beyond DMD and FSHD. ALS is one that we can talk about as well and we've got some thinking there and there will be more beyond that. But I think at the current time, we're very encouraged by the model data, both from DMD and FSHD.

人們對此感到非常興奮。事實上，我們已經證實 Apitegromab 能夠在如此嚴重的 SMA 疾病中增加肌肉量，這顯然對其他神經肌肉疾病有良好的治療效果。除了 DMD 和 FSHD 之外，還有其他跡象。ALS 也是我們可以討論的話題，我們對此有一些思考，而且還會有更多。但我認為目前，我們對 DMD 和 FSHD 的模型數據感到非常鼓舞。

We're working through details of exactly how to begin to study in those disorders and we'll share more details around that later in the year. But there's no question that an agent that is as strong as apitegromab clearly has to be investigated in additional indications.

我們正在研究如何開始研究這些疾病的具體細節，並將在今年稍後分享更多細節。但毫無疑問的是，像 apitegromab 這樣強效的藥物顯然需要在更多適應症中進行研究。

Gary Nachman, Raymond James.

蓋瑞納赫曼、雷蒙詹姆斯。

So if you get the SMA approval on the PDUFA, how quickly will you be able to launch? Will everything be completely in place already on the sales and marketing side, including with access and patient support programs? And how much commercial supply will you have at launch just in terms of meeting the demand? And then also if the proof-of-concept data in obesity are positive, just talk about the likely next steps with 439 after you file the IND. What type of Phase I study will you run? And how long before it could potentially move into a Phase II?

那麼，如果您獲得 SMA 對 PDUFA 的批准，您多快能夠啟動？銷售和行銷方面的一切是否已經完全到位，包括訪問和患者支援計劃？就滿足需求而言，你們在發佈時將提供多少商業供應？而且，如果肥胖症的概念驗證數據是積極的，那麼在提交 IND 後，只需討論 439 可能採取的後續步驟。您將進行哪種類型的第一階段研究？還有多久才有可能進入第二階段？

Yes. Thank you. And as Keith noted on the call, he's working with urgency here by mid-year to have the team in place for more commentary on like readiness to serve patients and approval. Keith?

是的。謝謝。正如基斯在電話中指出的那樣，他正在加緊努力，爭取在年中之前組建團隊，以便對為患者服務的準備情況和批准進行更多評論。基思？

Yes. Gary, thanks for the question. I mean, I think the first thing that I want to call out is that the team here has already been at work and has already been building, preparing for this launch for some time. We are fully staffed when it comes to our marketing team, and as I mentioned, our market access team. We have also -- we're fully staffed in our leadership team for our patient support programs.

是的。加里，謝謝你的提問。我的意思是，我想我首先要說的是，這裡的團隊已經開始工作，並且已經為這次發布進行了一段時間的準備。我們的行銷團隊以及我提到的市場准入團隊都配備了齊全的人員。我們的領導團隊也配備了充足的人員來負責病患支援計畫。

We will -- as I mentioned in the prepared remarks, we will have the entire commercial team fully staffed by mid-2025. So we should have a couple of months prior to launch. In regard to how soon will we launch after a September 22 date, we're going to be prepared to be out there the next day. I know that the supply chain team is working so that we can have product available to patients as soon as possible. And then I think the last thing that you had asked was in regard to supply. And I want to assure you that we have ample supply to be able to have a very successful launch.

正如我在準備好的演講中提到的那樣，到 2025 年中期，我們將擁有完整的商業團隊。所以我們應該在發布前有幾個月的時間。關於我們在 9 月 22 日之後多久會推出，我們將準備在第二天推出。我知道供應鏈團隊正在努力工作，以便我們能夠盡快向患者提供產品。然後我認為您問的最後一件事是關於供應的。我想向你們保證，我們有充足的供應，能夠確保發表會非常成功。

Thanks, Keith. And regarding like sort of the EMBRAZE study, the proof-of-concept. And I think, Gary, as you noted, how do we think about 439? As Akshay mentioned, we're moving forward with an anticipated IND for SRK-439 in Q3, no matter what. We see this as just another indication for us that we are the world leaders in myostatin biology and we're very excited to move this into first-in-human studies.

謝謝，基斯。關於 EMBRAZE 研究，概念驗證。加里，我認為，正如你所說，我們如何看待 439？正如 Akshay 所提到的，無論如何，我們都將在第三季推進 SRK-439 的預期 IND。我們認為這只是再次表明我們在肌肉生長抑制素生物學領域處於世界領先地位，我們非常高興將其推向首次人體研究。

The beautiful thing about SRK-439 is we have optionality. It can support our ambition in SMA and other additional rare, severe and debilitating neuromuscular disorders or depending upon the sort of results that we see with EMBRAZE.

SRK-439 的優點在於我們擁有可選性。它可以支持我們在 SMA 和其他罕見、嚴重和使人衰弱的神經肌肉疾病方面的雄心，或者取決於我們在 EMBRAZE 中看到的結果。

Depending upon our thoughts about further study there and how we might approach it, 439, as I think was previously noted by our team could have some optionality for us in a different space, that being cardiometabolic disorders and obesity. So we'll be guided by the data. We absolutely will sort of focus on what we see in this first exploratory readout in the EMBRAZE study and then we'll provide you all here in the coming month or two further plans for SRK-439.

根據我們對進一步研究的想法以及我們如何處理它，439，正如我認為我們的團隊之前指出的那樣，可以在不同的領域為我們帶來一些選擇，即心臟代謝紊亂和肥胖症。因此我們將以數據為指導。我們絕對會專注於 EMBRAZE 研究中首次探索性讀數所看到的內容，然後我們將在未來一兩個月內為大家提供 SRK-439 的進一步計劃。

Kripa Devarakonda, Truist.

Kripa Devarakonda，Truist。

Given that we're so close -- getting close to the PDUFA date, just a follow-up question from one of the prior analysts. Would you be able to provide any kind of metrics or guidance once the drug is approved or any color on how you see the early demand? And not sure how much you expect the recent executive order on drug pricing to have an impact on orphan disease area. But in light of that executive order, any comments on how you think about pricing in the US versus ex-US? I know it's early to give us exact numbers, but just qualitatively.

鑑於我們已經非常接近 PDUFA 日期，這只是先前一位分析師提出的後續問題。一旦該藥物獲得批准，您能否提供任何指標或指導，或您如何看待早期需求？而且不確定您認為最近有關藥品定價的行政命令會對孤兒病領域產生多大影響。但鑑於該行政命令，您對美國國內和美國境外的定價有何看法？我知道現在給出確切的數字還為時過早，但從品質上來說還是可以的。

Kripa, two great questions. Why don't I take sort of the President's executive order first and then Keith can comment a little bit about launch dynamics and kinetics. As you know, and I think you've just noted it in your question, it's very early to really comment on the President's executive order on MFN pricing.

Kripa，兩個很好的問題。我先來看看總統的行政命令，然後基斯可以對發射動力學和動力學發表一些評論。如你所知，我想您剛才在問題中也提到了這一點，現在就對總統關於最惠國定價的行政命令發表評論還為時過早。

However, it really does not change in any way our plans to commercialize apitegromab, not only in the US, but in Europe, Asia Pacific and Latin America. We do believe should any elements of the executive order be implemented, be implementable, it would obviously be better to have not yet established pricing for a therapy versus, let's just say, products that are already out there with established pricing.

然而，這確實不會以任何方式改變我們將 apitegromab 商業化的計劃，不僅在美國，而且在歐洲、亞太地區和拉丁美洲。我們確實相信，如果行政命令中的任何內容得以實施，並且是可以實施的，那麼顯然尚未確定治療方法的定價會比已經存在並確定價格的產品更好。

In all countries, we would expect that the price of apitegromab will be reflective of the rarity of SMA, the severity of SMA despite the use of all sort of SMN-targeted therapies, as we noted, still a loss of motor function despite the use of those over time. And then, of course, the strong value proposition that apitegromab may be able to provide to patients and families with SMA.

在所有國家，我們預計 apitegromab 的價格將反映出 SMA 的罕見性，儘管使用了所有類型的 SMN 標靶療法，SMA 的嚴重程度仍然如此，正如我們所注意到的，儘管隨著時間的推移使用這些療法，但仍然會出現運動功能的喪失。當然，apitegromab 可能能夠為 SMA 患者及其家庭提供強大的價值主張。

And then as I also noted a bit earlier, we think that given the rarity of the disease, apitegromab would not really impact tremendously any real budget of any magnitude of any single payer, let's just say, in the US or in any country around the world.

正如我之前提到的，我們認為，鑑於這種疾病的罕見性，apitegromab 不會對任何單一付款人的實際預算產生巨大影響，比如說，在美國或世界任何國家。

So we think no matter what happens with the President's executive order for MFN, we think we're going to be in a position of strength when we think about the launch of apitegromab globally for the 35,000 patients in the world that have received an SMN-targeted therapy. For a closer look at sort of your first part of your question on launch dynamics and kinetics, I'll ask Keith to comment.

因此，我們認為，無論總統關於 MFN 的行政命令如何，當我們考慮在全球範圍內為全球 35,000 名接受 SMN 標靶治療的患者推出 apitegromab 時，我們將處於優勢地位。為了更仔細地了解您關於發射動力學和動力學的問題的第一部分，我將請 Keith 進行評論。

Yes. Kripa, thank you for the question. First of all, in regard to guidance, we are not going to be providing guidance at this time. I can give you some aspects that from working in rare disease for now two decades, one thing that I'm very excited about the SMA marketplace is that 100% of newborn screening in the US. And as we noted in the prepared statements that we know of the 2/3 of SMA patients of the 10,000 in the U.S.

是的。Kripa，謝謝你的提問。首先，關於指導，我們目前不會提供指導。我可以提供你一些方面，從我從事罕見疾病工作二十年來的經驗來看，我對 SMA 市場感到非常興奮的一件事是美國 100% 的新生兒篩檢。正如我們在準備好的聲明中指出的那樣，我們知道美國 10,000 名 SMA 患者中有 2/3 是 SMA 患者。

that have already had an SMN-targeted therapy. These are good aspects to begin in a launch. Also the fact that we have the centers of excellence with the -- it's highly concentrated because of the Cure SMA model. All of these things give me optimism. Now think about this, these centers of excellence are also going to be many at your academic hospitals.

已經接受過 SMN 標靶治療。這些都是啟動時的良好開端。事實上，我們擁有卓越中心——由於 Cure SMA 模型，它高度集中。所有這些事情都讓我充滿樂觀。現在想想，你們的學術醫院也會有很多這樣的卓越中心。

So we will be going through formulary processes and such and some of them are quite timely. They're not just set based on our launch date, but when the academic centers and other centers are going through it. So we expect that between that as well as applying for a J-code that we would receive some time six-plus months later that we'll prepare for a consistent and steady launch.

因此，我們將經歷處方流程等，其中一些流程非常及時。它們不僅僅是根據我們的發布日期來設定的，而且是學術中心和其他中心進行的時間。因此，我們預計，在此期間以及申請六個多月後收到的 J 代碼期間，我們將為持續穩定的發布做好準備。

Marc Frahm, TD Cowen.

馬克·弗拉姆（Marc Frahm），TD Cowen。

Maybe just following up a little bit on Kripa's question before, just on launch trajectory. As you mentioned, the SMA population now has 100% newborn screening in the US. They've gotten very concentrated into these centers of excellence to receive SMN therapy. Like those would seem to be kind of tailwinds to the launch relative to prior SMA launches. But then while there's certainly unmet need, maybe it's not quite as dramatic as it was before the original SMA correctors launched, which would maybe be a headwind.

也許只是稍微跟進一下克里帕之前提出的問題，關於發射軌跡。正如您所說，美國目前對 SMA 族群的新生兒篩檢率為 100%。他們集中到這些卓越中心接受 SMN 治療。與之前的 SMA 發布相比，這些似乎對此次發布來說是一種順風。但是，雖然肯定存在未滿足的需求，但可能並不像最初的 SMA 校正器推出之前那麼引人注目，這可能是一個阻力。

I mean, do you think those net out and this -- we should look at prior SMA launches as a good proxy for the trajectory that apitegromab might have? And I guess, to the extent that you don't think those are good proxies, is there another -- other launches out there in the rare disease space that you think maybe are more analogous to what we should expect with apitegromab?

我的意思是，您是否認為這些網路和這個 - 我們應該將先前的 SMA 發布視為 apitegromab 可能具有的軌蹟的良好代理？我想，如果您認為這些不是好的代理，那麼在罕見疾病領域是否還有其他產品推出，您認為可能與我們對 apitegromab 的期望更相似？

It's a great question, Marc. I think, first of all, one of the things that our team is always focused on as opposed to looking at other sort of proxies or other launches, we just kind of look in the mirror and try to compete with ourselves and think about the best way that we can serve patients immediately and then over time. And so you're right, there's probably some headwinds. There's probably some tailwinds. But I think a couple of things that I would just underscore.

這是一個很好的問題，馬克。我認為，首先，我們的團隊始終關注的事情之一，而不是關注其他代理或其他發布，我們只是照鏡子，試圖與自己競爭，思考我們可以立即為患者提供服務的最佳方式，然後隨著時間的推移。所以你說得對，可能會有一些阻力。可能存在一些順風。但我認為有幾件事我只想強調一下。

SMN-targeted therapies in and of themselves with the longer-term data that's been presented absent of Scholar Rock have shown that there can be a return to the progressive motor function loss of the disease despite what happens earlier when treatment is initiated.

SMN 標靶治療本身以及 Scholar Rock 所缺乏的長期數據顯示，無論在治療開始時發生什麼，疾病都可能復發，並導致進行性運動功能喪失。

And then we ourselves showed in the SAPPHIRE study, obviously, at the time in which we were capturing patients and enrolling them in the study, there was overall loss of motor function rather than what we demonstrated with our primary endpoint, the gold standard Hammersmith scale, a gain of motor function. So we do think that there's a lot of urgency still for patients.

然後，我們自己在 SAPPHIRE 研究中表明，顯然，在我們捕獲患者並讓他們參與研究時，他們總體上存在運動功能的喪失，而不是我們通過主要終點、黃金標準 Hammersmith 量表所證明的運動功能的獲得。所以我們確實認為患者的情況仍然很迫切。

And I think Keith even commented on how that was underscored at the last month's presentation by Cure SMA of what patients and families were looking for. At the same time, we really want to play the long game independent of sort of launch trajectory.

我認為 Keith 甚至評論說，上個月 Cure SMA 的演講中強調了病人和家屬所尋求的東西。同時，我們確實希望能夠進行一場長期的、不受發射軌跡影響的比賽。

We want to build a team and a model to serve patients immediately and then over time for sort of a steady, consistent growth of our business by serving patients in a very meaningful way. I don't know if Keith would like to add a little bit more on to that as well. Keith?

我們希望建立一支團隊和一種模式，立即為患者提供服務，然後隨著時間的推移，透過以非常有意義的方式為患者服務，實現我們業務的穩定、持續成長。我不知道 Keith 是否也願意對此做進一步的補充。基思？

Yes. I mean, you bring up the point of this -- the launch compared to other SMN-targeted therapies when there was nothing else available, okay? So they truly had no other treatment. So I think this sense to urgency to be able to get to that product was great. As we take a look at the information, we find that patients that are on SMN-targeted therapies, most of them see their doctor on average 2 times per year.

是的。我的意思是，您提出了這一點——與其他 SMN 標靶療法相比，在沒有其他可用療法的情況下推出這種療法，好嗎？所以他們確實沒有其他治療方法。所以我認為，這種獲得該產品的緊迫感非常棒。當我們查看資訊時，我們發現接受 SMN 標靶治療的患者大多數每年平均看醫生 2 次。

So it's not like September 22 happens and they have an appointment the next week. So I just want to guide you on that. I agree with your statement that the fact that we know where these patients are is an advantage. However, there are going to be some headwinds, as David mentioned.

所以，這並不意味著 9 月 22 日就會發生這樣的事情，而他們下週就會有預約。所以我只是想在這方面指導你。我同意你的說法，我們知道這些病人在哪裡是一個優勢。然而，正如大衛所提到的，將會面臨一些阻力。

Evan Seigerman, BMO Capital.

埃文·西格曼（Evan Seigerman），BMO Capital。

Malcolm Hoffman on for Evan. Recently, we had noted some stronger rebound in Spinraza sales to start 2025. And we're hoping to get your updated thoughts on long-term changes that may occur in the SMA market, specifically with apitegromab being used in conjunction with Spinraza. Are you internally expecting any longer term growth from Spinraza that may benefit apitegromab upon launch?

馬爾科姆·霍夫曼替換埃文。最近，我們注意到 Spinraza 的銷量在 2025 年開始出現強勁反彈。我們希望了解您對 SMA 市場可能發生的長期變化的最新看法，特別是 apitegromab 與 Spinraza 聯合使用的情況。您是否在內部預期 Spinraza 的長期成長可能會使 apitegromab 上市後受益？

No, it's a great question. I think one of the things that we would note is that as Akshay shared earlier, in the SAPPHIRE study really in a prespecified way depending upon which SMN-targeted therapy a patient will receive, we feel like we can help all patients independent of whether or not they receive Spinraza or risdiplam.

不，這是一個很好的問題。我認為我們要注意的一件事是，正如 Akshay 之前分享的那樣，在 SAPPHIRE 研究中，我們確實以預先指定的方式根據患者將接受哪種 SMN 靶向治療，我們覺得我們可以幫助所有患者，無論他們是否接受 Spinraza 或 risdiplam。

We'll continue to sort of assess the nearly $5 billion annual market across the three different SMN-targeted therapies, whether or not it's the highly innovative gene therapy, Zolgensma or the other highly innovative SMN-targeted therapies like Spinraza and risdiplam. And we would just expect to follow those dynamics, but recognize with the SAPPHIRE data. And then as Akshay noted earlier in today's call, the upcoming under two study, the OPAL study, where we would expect more experience for apitegromab for patients who have received Zolgensma.

我們將繼續評估三種不同的 SMN 標靶療法的近 50 億美元年度市場，無論是高度創新的基因療法 Zolgensma 還是其他高度創新的 SMN 標靶療法，如 Spinraza 和 risdiplam。我們只是希望遵循這些動態，但要透過 SAPPHIRE 資料來識別。正如 Akshay 在今天的電話會議中早些時候指出的那樣，即將進行的兩項研究，即 OPAL 研究，我們期望在該研究中，能夠為接受過 Zolgensma 治療的患者提供更多關於 apitegromab 的經驗。

We think we're going to be in a position of strength to really help and provide potential transformational benefits for all patients that have received SMN-targeted therapies over time. Thank you for your question.

我們認為，我們將處於有利地位，真正為所有接受過 SMN 標靶治療的患者提供幫助，並帶來潛在的轉化益處。感謝您的提問。

Andres Maldonado, H.C. Wainwright.

安德烈斯·馬爾多納多、H.C. 溫賴特。

Just a quick one for me. Given progress towards US launch and your ongoing readiness in Europe, I guess, how are you evaluating the potential to secure a commercial partner for Europe? And in this context, obviously, you want to fire on all cylinders across the pipeline, but how would you prioritize the additional indications for apitegromab in this situation?

對我來說只是一個快速的步驟。鑑於美國發布的進展以及您在歐洲的持續準備，我想，您如何評估為歐洲找到商業夥伴的潛力？在這種情況下，顯然您希望全力以赴，但在這種情況下，您將如何優先考慮 Apitegromab 的其他適應症？

Yes. Thank you. I think we noted this just a few weeks ago on our April 28 call. Given the experience that this collective team has had between Alexion, Alnylam, argenx, we feel like there is nobody better suited to serve patients globally than us directly. So it is not a priority of ours to think about a partner outside of the US.

是的。謝謝。我想我們在幾週前的 4 月 28 日電話會議上就提到過這一點。鑑於這個團隊在 Alexion、Alnylam、argenx 之間累積的經驗，我們覺得沒有人比我們更適合直接為全球患者提供服務。因此，考慮美國以外的合作夥伴並不是我們的首要任務。

We feel like this is something that we know well, and in fact, do well. And we'll continue to run a playbook that not only do we know the playbook, we feel like we wrote that playbook. As it relates to other indications, as Akshay noted, will be data-driven. The team has been doing some wonderful work in looking preclinically at additional rare, severe and debilitating neuromuscular diseases. And Akshay will be providing further guidance on that towards the end of this year and into next.

我們覺得這是我們很了解的事情，而且事實上我們做得很好。我們將繼續執行劇本，我們不僅了解劇本，而且感覺是我們編寫了劇本。正如 Akshay 所指出的，它與其他適應症有關，將由數據驅動。該團隊在臨床前研究其他罕見、嚴重和使人衰弱的神經肌肉疾病方面做了一些出色的工作。Akshay 將在今年年底和明年就此提供進一步的指引。

Thank you.

謝謝。

Dennis Kennedy, LifeSci Capital.

丹尼斯·肯尼迪，LifeSci Capital。

As we look towards the EMBRAZE data in June, can you just help frame expectations for the tirzepatide monotherapy arm? Specifically, how much of the lean mass loss could we expect at one year with tirzepatide do you think typically occurs by week 24? And related to that, do you think eight weeks of follow-up post-treatment is sufficient time to demonstrate a weight regain in patients in the tirzepatide monotherapy arm?

當我們展望 6 月的 EMBRAZE 數據時，您能否幫助我們制定對 tirzepatide 單藥治療組的預期？具體來說，您認為使用 tirzepatide 一年後，我們預計第 24 週時瘦體重會減少多少？與此相關，您是否認為治療後八週的追蹤時間足以證明 tirzepatide 單藥治療組患者的體重恢復？

Yes, Dennis, these are great questions. And in fact, I think within your questions, you sort of highlight some of the limitations for us in sort of a 24-week endpoint and then eight weeks following. But nonetheless, as Akshay and I have noted, we feel like it's important to understand for the first time if there is a role that we can play. Akshay?

是的，丹尼斯，這些都是很好的問題。事實上，我認為在您的問題中，您強調了我們在 24 週終點和隨後 8 週的一些限制。但儘管如此，正如阿克沙伊和我所指出的，我們覺得第一次了解我們是否可以發揮一定作用是很重要的。阿克謝？

Yes, thanks. So Dennis, I mean, tirzepatide consistently has shown loss of lean mass as of the other GLP-1. That mass is symmetrical to the overall loss in body mass. And so you can expect that at week 24, about 25% to 30% of the weight loss that will have occurred in the tirzepatide alone arm will be due to loss of muscle. We're projecting that based on historical data.

是的，謝謝。所以丹尼斯，我的意思是，與其他 GLP-1 一樣，tirzepatide 一直表現出瘦體重的損失。此質量與整體體重損失是對稱的。因此，你可以預期，在第 24 週，單獨使用 tirzepatide 的組別中大約 25% 到 30% 的體重減輕將是由於肌肉損失造成的。我們根據歷史資料進行預測。

There's no reason to believe that it will be any different in the context of this study. Now will that be the maximal amount of lean mass loss at week 24? I don't think so, because in the pivotal studies, tirzepatide was studied for much longer. And overall, the impact on muscle mass is even greater, obviously, as therapy continues and patients lose more weight. But within the context of EMBRAZE to 1/3 of weight loss at week 24 will be mean mass loss we expect.

沒有理由相信在本研究的背景下情況會有所不同。那麼這會是第 24 週瘦體重損失的最大量嗎？我不這麼認為，因為在關鍵研究中，tirzepatide 的研究時間更長。總體而言，隨著治療的持續和患者體重的減輕，對肌肉質量的影響顯然會更大。但在 EMBRAZE 的背景下，我們預計第 24 週減重將達到平均質量損失的 1/3。

Your other point about is 8 weeks of follow-up sufficient? Well, look, this study was an exploratory study to understand the potential of apitegromab in a pure clean, safe potent anti-myostatin approach in the context of obesity. I don't think the 8-week follow-up answers the whole question, but you can anticipate that there will be some weight regain during that period and the trajectory of that will be quite important to monitor between the two arms.

您另一個問題是，8 週的跟進是否足夠？嗯，看，這項研究是一項探索性研究，旨在了解 apitegromab 在肥胖症背景下作為純淨、安全、強效的抗肌生長抑制素方法的潛力。我認為 8 週的追蹤並不能回答整個問題，但你可以預見在此期間體重會有所恢復，並且監測兩組之間的變化軌跡非常重要。

At this time, I am showing no further questions in the queue.

目前，隊列中沒有其他問題。

Thank you, operator. And thanks for everybody joining the call today and we'll look forward to continuing to update you and keeping you apprised of our progress as an organization. Thank you.

謝謝您，接線生。感謝大家今天參加電話會議，我們期待繼續向你們通報最新情況，並讓你們了解我們作為一個組織的進展。謝謝。

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

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。