Scholar Rock Holding Corp (SRRK) 2025 Q2 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Scholar Rock's second-quarter 2025 business update conference call. (Operator Instructions) This call is being recorded on Wednesday, August 6, 2025.

女士們、先生們，早安，歡迎參加 Scholar Rock 2025 年第二季業務更新電話會議。（操作員指示）此通話於 2025 年 8 月 6 日星期三錄製。

I would like to turn the conference over to Scholar Rock. Please go ahead.

我想將會議交給 Scholar Rock。請繼續。

Good morning. I'm Rashmi Nafsinger, Vice President of Corporate Affairs and Investor Relations at Scholar Rock. With me today are David Hallal, Chairman and Chief Executive Officer; Akshay Vaishnaw, President of R&D; Keith Woods, Chief Operating Officer; and Vikas Sinha, Chief Financial Officer. For those of you participating via conference call, the accompanying slides can be accessed by going to the event section of the investor's page on our website.

早安.我是 Scholar Rock 公司事務和投資者關係副總裁 Rashmi Nafsinger。今天與我一起出席的有董事長兼執行長 David Hallal、研發總裁 Akshay Vaishnaw、營運長 Keith Woods 和財務長 Vikas Sinha。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。

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 for apitegromab, and Vikas will provide commentary on our financials, and then we will open the call for questions.

在今天的電話會議中，如投影片 2 所示，David 將提供介紹性發言並提供一般業務更新。Akshay 將審查我們的臨床和監管進展。Keith 將提供有關 apitegromab 商業準備活動的最新情況，Vikas 將對我們的財務狀況發表評論，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 feller 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 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 Feller Rock 的預期、計劃和前景做出各種聲明，這些聲明構成《1995 年私人證券訴訟改革法案》安全港條款規定的前瞻性聲明。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, Rashmi, and good morning. Thanks to everyone for joining our Q2 update call today. This is an exciting time of great strength and opportunity at Scholar Rock. We are scaling for the next phase of growth as a commercial stage fully integrated global biopharmaceutical company.

謝謝，拉什米，早安。感謝大家今天參加我們的第二季更新電話會議。這是 Scholar Rock 充滿力量和機會的激動人心的時刻。作為一家商業階段完全整合的全球生物製藥公司，我們正在為下一階段的成長做準備。

Our three core priorities drive our vision of becoming a global biotech powerhouse. First, apitegromab regulatory approvals, and following those approvals, the US launch of apitegromab for children and adults with SMA. followed by a series of country launches in the coming years, starting in Europe with Germany next year. Second, expand apitegromab into additional rare, severe, and debilitating neuromuscular diseases. And third, disciplined capital allocation to support our high value commercial and development initiatives.

我們的三大核心優先事項推動著我們成為全球生物技術強國的願景。首先，apitegromab 獲得監管部門批准，隨後，美國將推出用於治療 SMA 兒童和成人的 apitegromab。接下來幾年，該藥物將在一系列國家推出，首先是歐洲，明年是德國。其次，將 apitegromab 擴展到其他罕見、嚴重和使人衰弱的神經肌肉疾病。第三，嚴格的資本配置，以支持我們的高價值商業和發展計劃。

With respect to our ongoing regulatory processes, we are working collaboratively with the FDA and European Medicines Agency. We are also urgently preparing for our US commercial launch as our BLA has been accepted under priority review with a target action date of September 22.

關於我們正在進行的監管流程，我們正在與 FDA 和歐洲藥品管理局合作。我們也在緊急準備美國的商業發布，因為我們的 BLA 已被優先審查，目標行動日期為 9 月 22 日。

As you are aware, GXP inspections are part of the standard FDA review process, including those relating to pre-approval inspections, clinical trial site inspections, and manufacturing site inspections. These inspections often result in observations requiring responses within the review cycle. The FDA has conducted a full set of inspections and as part of this process, noted observations at two of our CDMOs.

如您所知，GXP 檢查是標準 FDA 審查流程的一部分，包括與批准前檢查、臨床試驗現場檢查和製造現場檢查相關的檢查。這些檢查通常會導致需要在審查週期內回應的觀察結果。FDA 已進行了全套檢查，並作為此過程的一部分，對我們的兩個 CDMO 進行了記錄觀察。

On Friday, August 1, another pharmaceutical company disclosed observations as part of an FDA general site inspection at their filler, Catalent, Indiana, which was recently acquired by Novo Nordisk. Our fill finish for apitegromab is conducted at the same site. The general site inspection of the facility was not specific to apitegromab. Novo Nordisk submitted a robust and comprehensive response earlier this week to the observations noted by the FDA.

8 月 1 日星期五，另一家製藥公司在其位於印第安納州的灌裝廠 Catalent 進行 FDA 一般現場檢查時披露了觀察結果，該公司最近被 Novo Nordisk 收購。我們對 apitegromab 的填充完成是在同一地點進行的。對該設施的一般現場檢查並非針對 apitegromab。本週早些時候，諾和諾德針對 FDA 指出的意見提交了有力且全面的回應。

For the other CDMO observations were received at the conclusion of a pre-licensing inspection, and a comprehensive response will be submitted within the next week. We continue to work collaboratively with the agency. Importantly, the FDA recently completed our late cycle meeting following both site inspections. We are encouraged by the dialogue with the agency at the late cycle meeting where the FDA indicated that they are working towards completing the review of our BLA by our September 22nd PDUFA date.

對於其他 CDMO 的意見，在許可前檢查結束時已收到，並將在下週內提交全面的答复。我們將繼續與該機構合作。重要的是，FDA 最近在兩次現場檢查後完成了我們的後期週期會議。我們對在後期週期會議上與該機構的對話感到鼓舞，FDA 表示他們正在努力在 9 月 22 日 PDUFA 日期之前完成對我們的 BLA 的審查。

Earlier this year, we also filed our MAA for apitegromab in the EU, and we continue to work with the European Medicines Agency and expect a potential approval near mid-2026. We are planning for Germany to be our first European country launch with an ambition to reach patients with SMA across all of Europe, followed by additional countries in Asia Pacific and Latin America over time.

今年早些時候，我們也在歐盟提交了 apitegromab 的 MAA，我們將繼續與歐洲藥品管理局合作，預計該藥物可能在 2026 年中期獲得批准。我們計劃將德國作為我們在歐洲推出的第一個國家，目標是覆蓋整個歐洲的 SMA 患者，隨後逐步涵蓋亞太地區和拉丁美洲的其他國家。

The global opportunity with apitegromab and SMA alone offers the potential for many years of sustainable growth through the end of this decade and into the next. Along with Keith, Akshay, and Vikas, and the other leaders at the company, we have bolstered Scholar Rock's capabilities as we advance our mission to deliver apitegromab to children and adults with SMA. This is indeed what we know well and what we do well.

光是 Apitegromab 和 SMA 帶來的全球機會就有可能在本世紀末乃至下一個十年實現多年的永續成長。我們與 Keith、Akshay、Vikas 和公司其他領導者一起，增強了 Scholar Rock 的能力，推進我們的使命，為患有 SMA 的兒童和成人提供 apitegromab。這確實是我們熟知的、擅長的事。

In addition to the large opportunity to serve patients with SMA, we will continue to expand our pipeline by planning additional opportunities for apitegromab for children and adults suffering with additional rare, severe, and debilitating neuromuscular disorders, which Akshay will discuss in more detail shortly.

除了為 SMA 患者服務的巨大機會之外，我們還將繼續擴大我們的產品線，為患有其他罕見、嚴重和衰弱性神經肌肉疾病的兒童和成人規劃更多的 apitegromab 治療機會，Akshay 將很快對此進行更詳細的討論。

Importantly, to grow Scholar Rock, we are taking a thoughtful, deliberate approach to capital allocation by staging our investments along with our commercial progress in serving the SMA community. Q2 has been exceptionally productive.

重要的是，為了發展 Scholar Rock，我們採取了深思熟慮、謹慎的資本配置方式，將投資與為 SMA 社群提供服務的商業進展結合起來。第二季的成果非常顯著。

In the quarter when Keith joined our team as our Chief Operating Officer, he brought a proven track record of building and leading teams to deliver highly successful rare disease global launches in the neuromuscular therapeutic area, including most recently with [vivgar]. Under Keith's leadership, we have assembled an exceptionally experienced, talented, and patient-centric field team committed to the SMA community. Impressively, over just a few months, the team is on board, trained, and deployed, and are ready to deliver a apitegromab to the SMA community pending approval in September.

在 Keith 加入我們的團隊擔任營運長的這個季度，他帶來了在組建和領導團隊方面的成功經驗，在神經肌肉治療領域成功實現了罕見疾病的全球上市，包括最近與[活力]。在 Keith 的領導下，我們組建了一支經驗豐富、才華橫溢、以患者為中心的現場團隊，致力於服務 SMA 社群。令人印象深刻的是，僅用了幾個月的時間，該團隊就已加入、培訓和部署完畢，並準備在 9 月份獲得批准後向 SMA 社區提供 apitegromab。

Despite currently available treatments that have been approved over the past 10 years, we are acutely aware that muscle strength and motor function are among the top unmet needs in SMA, which we believe can be addressed with the potential approval of apitegromab, the world's first and only muscle targeted therapy to deliver statistically significant and clinically meaningful improvements in motor function in a pivotal Phase 3 trial.

儘管目前已有的治療方法在過去 10 年內獲得批准，但我們敏銳地意識到，肌肉力量和運動功能是 SMA 中最大的未滿足需求之一，我們相信，隨著 apitegromab 的潛在批准，這一問題可以得到解決。 apitegromab 是世界上第一個也是唯一一個在關鍵的 3 期試驗中在運動功能方面實現統計學上顯著和臨床上有意義的改善的肌肉靶向治療藥物。

I would like to now turn briefly to the readout of the positive Phase 2 EMBRAZE proof-of-concept study in Q2. The goal of EMBRAZE was to understand the role of targeting myostatin in the treatment of patients with obesity. We are pleased that the EMRAZE study met the primary entry point with patients on tirzepatide. Apitegromab increased lean mass preservation by greater than 54% compared to tirzepatide alone, with AP value equal to 0.001, with an encouraging safety profile.

現在我想簡要介紹第二季積極的第二階段 EMBRAZE 概念驗證研究的結果。EMBRAZE 的目標是了解針對肌肉生長抑制素在肥胖症患者治療中的作用。我們很高興 EMRAZE 研究滿足了使用 tirzepatide 的患者的主要切入點。與單獨使用 tirzepatide 相比，Apitegromab 使瘦體重保存率提高了 54% 以上，AP 值等於 0.001，且安全性令人鼓舞。

We are very pleased that the highly selective anti-myostatin approach from our innovative platform continues to deliver. While we remain focused on advancing apitegromab in clinical development for additional rare, severe, and debilitating neuromuscular disorders, EMBRAZE raises the exciting possibility to partner our potent and selective approach to targeting myostatin.

我們非常高興，我們創新平台的高選擇性抗肌生長抑制素方法能夠繼續發揮作用。雖然我們仍然專注於推進 apitegromab 在臨床開發中用於治療其他罕見、嚴重和使人衰弱的神經肌肉疾病，但 EMBRAZE 提出了令人興奮的可能性，可以與我們針對肌肉生長抑制素的強效和選擇性方法相結合。

As we communicated at EMBRAZE data readout, in addition to SRK-439, we have a number of earlier stage research assets, both anti-myostatin antibodies and the fusion of those with GLPs, which we think have the potential to be meaningful therapeutic candidates in the future. As we look forward, we remain very focused on the nearly 35,000 patients with SMA globally that have received SMN-targeted therapies.

正如我們在 EMBRAZE 數據讀取中所說的那樣，除了 SRK-439 之外，我們還有許多早期階段的研究資產，包括抗肌肉生長抑制素抗體以及與 GLP 的融合，我們認為它們有可能成為未來有意義的治療候選藥物。展望未來，我們仍將高度關注全球近 35,000 名接受 SMN 標靶治療的 SMA 患者。

While we anticipate the global launch will commence in the US and Q3, pending regulatory approvals, we are also making preparations to serve children and adults with SMA in Europe, Asia Pacific, and Latin America. Our ambition at Scholar Rock is that globally, any patient with SMA who can benefit from apitegromab should have access to apitegromab.

雖然我們預計全球發布將在美國和第三季開始，但等待監管部門的批准，但我們也在為歐洲、亞太地區和拉丁美洲的 SMA 兒童和成人提供服務做準備。Scholar Rock 的目標是，在全球範圍內，任何能夠從 apitegromab 中受益的 SMA 患者都應該能夠使用 apitegromab。

At this point, I'll turn the call over to Akshay to provide a more detailed update on our R&D progress. Akshay?

現在，我將把電話轉給 Akshay，以提供有關我們研發進展的更詳細的更新。阿克謝？

Thanks, David, and good morning, everyone. SMA is a rare severe neuromuscular disease, resulting in irreversible loss of motor neurons and progressive muscle wasting that causes continuous motor function decline throughout life, diminishing the independence of both children and adults.

謝謝，大衛，大家早安。SMA 是一種罕見的嚴重神經肌肉疾病，導致運動神經元不可逆的損失和進行性肌肉萎縮，引起終生持續的運動功能衰退，從而降低兒童和成人的獨立性。

There's been progress over the last decade with new therapies for SMA. However, despite the chronic use of these SMN correctors, SMA remains a devastating disease for children, adults, and their families living with the disorder. Patients experience muscle wasting that impacts all aspects of mobility, basic activities of daily living like eating, washing, and dressing, and the ability to live independently.

過去十年，SMA 的新療法取得了進展。然而，儘管長期使用這些 SMN 矯正器，SMA 仍然對患有該疾病的兒童、成人及其家人來說是一種毀滅性的疾病。患者會出現肌肉萎縮，影響到各方面的活動能力、進食、洗漱、穿衣等日常生活的基本活動以及獨立生活的能力。

The motor unit has two key components: the motor neuron itself and muscle. SMN-targeted therapies are aimed at preventing motor neuron loss, but muscle, the principal organ effect in SMA, has not been directly addressed. Given that motor function depends not only on neuronal signaling, but also on muscle responsiveness, approaches that target muscle from the start are urgently needed.

運動單位有兩個關鍵組成部分：運動神經元本身和肌肉。SMN 標靶治療旨在防止運動神經元流失，但肌肉（SMA 的主要器官效應）尚未直接解決。鑑於運動功能不僅取決於神經訊號，還取決於肌肉反應，因此迫切需要從一開始就針對肌肉的方法。

Our SAPPHIRE trials showed that in those receiving chronic ongoing SMN-targeted therapies, 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 motor function as measured by the gold standard Hammersmith motor function scale, while patients on placebo worsened.

我們的 SAPPHIRE 試驗表明，對於接受長期持續 SMN 標靶治療的患者，apitegromab 有可能逆轉 SMA 從運動功能喪失到運動功能恢復的進展。具體而言，研究表明，以黃金標準哈默史密斯運動功能量表衡量，患者的運動功能有顯著改善，而服用安慰劑的患者則惡化。

Importantly, patients treated with apitegromab had an approximately three-fold higher chance of a 3 point or greater increase in Hammersmith versus those on placebo. In addition, there was a consistent 1.8% improvement in Hammersmith across all ages in our Phase 3 trial. Along with the encouraging safety profile, the SAPPHIRE data suggests that apitegromab has great potential to provide clinically significant benefit to patients with SMA despite the chronic use of 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 3 分或更多的可能性大約高出三倍。此外，在我們的第 3 階段試驗中，Hammersmith 各年齡層患者的病情均持續改善了 1.8%。除了令人鼓舞的安全性之外，SAPPHIRE 數據還表明，儘管長期使用 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。

As David mentioned, a BLA was accepted under prior review, which recognizes the potential of apitegromab to be a treatment for a serious or life-threatening condition or to provide a significant improvement in safety or effectiveness over existing treatments. I'm excited that our team continues to work collaboratively with regulators towards the September 22 PDUFA date. With respect to Europe, the [MA] was validated by EMA, and we look forward to further review and the approval of apitegromab in Europe in 2026.

正如 David 所提到的，BLA 已在先前的審查中被接受，這承認了 apitegromab 具有治療嚴重或危及生命的疾病的潛力，或者在安全性或有效性方面比現有治療方法有顯著的提高。我很高興我們的團隊繼續與監管機構合作，爭取在 9 月 22 日的 PDUFA 日期之前完成。就歐洲而言，[MA] 已獲得 EMA 的驗證，我們期待 2026 年歐洲對 apitegromab 進行進一步審查並獲得批准。

Turning to the next slide, I'm pleased to report that we're on track to initiate the Phase 2 OPAL trial in children under the age of 2. The study is evaluating two different doses over the course of 48 weeks and will assess PK, PD, efficacy, and safety. The enrollment criteria abroad in infants and toddler toddlers may be enrolled with any approved SMN-targeted therapy, including gene therapy.

翻到下一張投影片，我很高興地報告，我們正按計畫啟動 2 歲以下兒童的第 2 階段 OPAL 試驗。該研究正在 48 週內評估兩種不同劑量，並將評估 PK、PD、功效和安全性。國外嬰幼兒的入組標準 嬰幼兒可以接受任何已核准的SMN標靶治療，包括基因治療。

Early intervention with apitegromab in the OPAL study could support muscle during a critical early developmental phase, complementing SMN-targeted therapies that aim to preserve most neurons. By promoting muscle growth, when both motor neurons and muscles are still forming, Apitegromab has a unique opportunity to improve motor outcomes in babies and toddlers with SMA.

OPAL 研究中對 apitegromab 進行早期幹預可以在關鍵的早期發育階段支持肌肉，補充旨在保留大多數神經元的 SMN 靶向療法。透過促進肌肉生長，當運動神經元和肌肉仍在形成時，Apitegromab 具有改善 SMA 嬰兒和幼兒運動結果的獨特機會。

Turning to our plans for the study of apitegromab in additional rare and severe neuromuscular disease, at the outset, let me state that the potential to prevent muscle loss and enhance muscle growth by blocking myostatin holds great potential across a wide array of diseases. Here you see just two examples of that potential in mouse models of the severe debilitating disorders, Duchenne muscular dystrophy or DMD, and facioscapulohumeral muscular dystrophy or FSHD.

談到我們對 Apitegromab 在其他罕見和嚴重神經肌肉疾病中的研究計劃，首先我要指出的是，透過阻斷肌生長抑制素來防止肌肉損失和增強肌肉生長的潛力在多種疾病中都具有巨大的潛力。這裡您看到的只是嚴重衰弱性疾病小鼠模型中這種潛力的兩個例子，即杜氏肌肉營養不良症或 DMD 和麵肩肱型肌肉營養不良症或 FSHD。

In the DMD model on the left, the inclusion of an anti-myostatin antibody in mice receiving an exon skipping oligo is associated with a dramatic increase in the level of dystrophin and a resulting increase in muscle force. FSHD is a neuromuscular disease resulting in patchy changes with affected and unaffected motor fibers.

在左側的 DMD 模型中，接受外顯子跳躍寡核苷酸的小鼠體內加入抗肌生長抑制素抗體，與肌營養不良蛋白水平的急劇增加以及隨之而來的肌肉力量的增加有關。FSHD 是一種神經肌肉疾病，會導致受影響和不受影響的運動纖維出現斑塊狀變化。

In the FSHD model on the right, treatment with an anti-myostatin antibody results in hypertrophy of unaffected motor units and once again an impressive gain in motor function. We continue our evaluations of an anti-myostatin approach in DMD and FSHD as well as in other models of disease, and we'll initiate the study of apitegromab in an additional neuromuscular indication by the end of 2025.

在右側的 FSHD 模型中，使用抗肌生長抑制素抗體治療會導致未受影響的運動單位肥大，並再次顯著提高運動功能。我們將繼續評估 DMD 和 FSHD 以及其他疾病模型中的抗肌生長抑制素方法，並將在 2025 年底之前啟動 apitegromab 在其他神經肌肉適應症的研究。

In June, we were gratified to announce the exciting results from our EMBRAZE proof-of-concept study. David has covered those findings, including that the study met the primary endpoint with an encouraging safety profile. These findings are important as preservation of lean mass during GLP-1 mediated weight loss has the potential to enhance both cardio metabolic and musculoskeletal health.

6 月，我們很高興地宣布了 EMBRAZE 概念驗證研究的令人興奮的結果。David 已經報導了這些發現，包括研究達到了主要終點並具有令人鼓舞的安全性。這些發現很重要，因為在 GLP-1 介導的減肥期間保持瘦體重有可能增強心臟代謝和肌肉骨骼健康。

Next, we continue to advance our world leading anti-myostatin platform beyond apitegromab. Further to our commitment to neuromuscular disease, SRK-439 builds on the validated approach that delivered apitegromab. There's great potential for SRK-439 to be an infrequent, potent, subcutaneous anti-myostatin antibody, and we look forward to exploring its potential as another innovative Scholar Rock therapy for patients suffering with severe neuromuscular disorders.

接下來，我們將繼續推進我們世界領先的抗肌生長抑制素平台，超越apitegromab。為了進一步履行我們對神經肌肉疾病的承諾，SRK-439 以已驗證的 apitegromab 方法為基礎。SRK-439 具有成為一種罕見、強效、皮下抗肌生長抑制素抗體的巨大潛力，我們期待探索其作為另一種創新 Scholar Rock 療法治療嚴重神經肌肉疾病患者的潛力。

We remain on track to file the I&D application for SRK-439 to support the first in human study later this year. I'd like to conclude by reiterating our key priorities. Number one, drive the US approval of a apitegromab in Q3025 and advance the EU toward approval in 2026. Number two, initiate a study of apitegromab for infants and toddlers with SMA under the age of 2 in Q3 '25. Number three, initiate clinical development of apitegromab in at least one additional neuromuscular indication by the end of '25. And finally, file an R&D for SRK-439 in the second half of '25.

我們將繼續按計劃提交 SRK-439 的 I&D 申請，以支持今年稍後進行的首次人體研究。最後，我想重申我們的主要優先事項。第一，推動美國在 2025 年第三季批准 Apitegromab，並推動歐盟在 2026 年批准。第二，在 2025 年第三季啟動 2 歲以下 SMA 嬰幼兒的 apitegromab 研究。第三，到 25 年底，啟動 Apitegromab 在至少一種額外神經肌肉適應症的臨床發展。最後，在 25 年下半年提交 SRK-439 的研發申請。

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

說完這些，我將把電話轉給 Keith 提供商業更新。基思？

Thanks, Akshay, and good morning, everyone. With apitegromab advancing through the regulatory processes in the US and Europe, we are preparing to usher in a new era for the treatment of children and adults with SMA. This is a progressive and devastating disease that leads to loss of mobility, limited activities of daily living, and a lack of independence. If muscle is left untreated, it can result in irreversible atrophy.

謝謝，Akshay，大家早安。隨著apitegromab在美國和歐洲的監管程序不斷推進，我們正準備迎來兒童和成人SMA治療的新時代。這是一種進行性、破壞性的疾病，會導致行動能力喪失、日常生活活動受限、缺乏獨立性。如果不治療肌肉，可能會導致不可逆的萎縮。

We're excited about apitegromab's potential as the first and only muscle targeted treatment to show clinically meaningful and statistically significant motor function improvements in children and adults living with SMA.

我們很高興看到 apitegromab 具有潛力成為第一個也是唯一一個針對肌肉的治療方法，能夠為患有 SMA 的兒童和成人帶來具有臨床意義和統計意義的運動功能改善。

The SMA community is calling for a treatment to address progressive muscle degeneration and motor function loss. To underscore this, a 2025 Cure SMA survey showed that 90% of patients report that their greatest unmet need is to gain muscle strength. 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.

SMA 社群正在呼籲採取治療方法來解決進行性肌肉退化和運動功能喪失的問題。為了強調這一點，2025 年治癒 SMA 調查顯示，90% 的患者報告他們最大的未滿足需求是增強肌肉力量。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。

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. We are on track with the preparation of the global launch of apitegromab, starting with the US.

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。我們正在按計劃推進 Apitegromab 的全球上市準備工作，首先在美國上市。

Based on our September 22 PDUFA date, we will execute our commercial launch of apitegromab immediately following our FDA approval. In Europe, our MAA is under review by the European Medicines Agency, and we are preparing to launch upon approval in 2026.

根據我們 9 月 22 日的 PDUFA 日期，我們將在獲得 FDA 批准後立即進行 apitegromab 的商業發布。在歐洲，我們的 MAA 正在接受歐洲藥品管理局的審查，我們準備在 2026 年獲得批准後上市。

I'm excited to announce that as of today, under the leadership of our US General Manager and Chief Brand Officer, Rebecca McLeod, our US customer facing team is fully on board, trained, and now deployed in the field. Our team is currently engaging with the SMA treatment centers, key opinion leaders, and both public and private payers.

我很高興地宣布，從今天起，在我們美國總經理兼首席品牌長 Rebecca McLeod 的領導下，我們面向美國的客戶服務團隊已全面加入、接受培訓並部署到現場。我們的團隊目前正在與 SMA 治療中心、關鍵意見領袖以及公共和私人付款人合作。

We are impressed by the talent, the extensive rare disease experience, and the passion to serve patients that our new team members bring. The team is comprised of many professionals that have substantial experience in serving the SMA community for the broader neuromuscular disease community, and we are united by a commitment to serving these patients.

我們新團隊成員的才華、豐富的罕見疾病經驗以及為患者服務的熱情給我們留下了深刻的印象。該團隊由許多專業人士組成，他們在為 SMA 社群和更廣泛的神經肌肉疾病社群服務方面擁有豐富的經驗，我們團結一致，致力於為這些患者提供服務。

Today in the US there are approximately 10,000 patients living with SMA and roughly two-thirds of them have received an SMN-targeted therapy. These investments we are making position us to reach these patients with apitegromab and we'll provide a blueprint for our global rollout.

目前，美國約有 1 萬名 SMA 患者，其中約三分之二接受了針對 SMN 的治療。我們正在進行的這些投資使我們能夠為這些患者提供 apitegromab，並且我們將為我們的全球推廣提供藍圖。

Globally, there are approximately 35 patients with SMA that have already received an SMN-targeted therapy, and we have an enormous opportunity to make a meaningful difference with apitegromab with the potential to reverse progression of SMA from a loss of motor function to a gain of motor function. The entire Scholar Rock team is ready to serve the SMA community, and we will move with a sense of urgency to deliver apitegromab to them following approval.

在全球範圍內，大約有 35 名 SMA 患者已經接受了 SMN 標靶治療，我們有巨大的機會透過 apitegromab 發揮有意義的作用，有可能逆轉 SMA 從運動功能喪失到運動功能恢復的進程。整個 Scholar Rock 團隊已準備好為 SMA 社區提供服務，我們將在獲得批准後儘快向他們提供 apitegromab。

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 Q2 business update and provide insights into how we are thinking about resource allocation in the future. The opportunity with apitegromab and 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.

謝謝你，基思，大家早安。我很高興提供我們第二季的業務更新，並提供有關我們如何考慮未來資源分配的見解。光是 apitegromab 和 SMA 這一機會就提供了多年可持續成長的潛力，並將使我們能夠對我們的產品線進行策略性深思熟慮的投資，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。

We ended the quarter with $295 million. During the quarter, we continued to increase our investment in infrastructure to support commercial readiness and our supply of apitegromab to support the launch. As we look ahead, we are prioritizing the commercial launch and our ongoing clinical programs. We have an additional $50 million under our debt facility that we can draw down this year, and we also anticipate receiving approximately $16 million from exercise of outstanding common warrants by year end, bringing our anticipated runway into 2027.

本季結束時我們的營收為 2.95 億美元。在本季度，我們繼續增加對基礎設施的投資以支持商業準備，並增加對 apitegromab 的供應以支援產品發布。展望未來，我們將優先考慮商業發布和正在進行的臨床項目。我們還有 5,000 萬美元的債務融資可供今年提取，我們也預計到年底將透過行使未償還的普通股認股權證獲得約 1,600 萬美元，使我們的預期跑道能夠持續到 2027 年。

Additionally, $50 million is available under our debt facility post approval to support the upcoming launch. We also anticipate monetizing our priority if you voucher following approval. We continue to operate with a tight financial plan, and we'll share more details over the next few quarters. As a reminder, we will continue to focus on driving strong performance with financial discipline. Next, investing in capital efficient commercial build out and thoughtful capital allocation to advance our pipeline.

此外，我們的債務融資工具獲批後將提供 5,000 萬美元，以支持即將推出的產品。如果您在批准後提供憑證，我們也希望將我們的優先權貨幣化。我們將繼續執行嚴格的財務計劃，並將在接下來的幾個季度分享更多細節。提醒一下，我們將繼續致力於透過財務紀律來推動強勁的業績。接下來，投資資本高效的商業建設和周到的資本配置來推進我們的管道。

With that, I will turn it back to David. David?

說完這些，我就把話題轉回給大衛。戴維？

Thanks, Vikas. In closing, we are committed to successfully executing on these key priorities which position us to transform Scholar Rock into a premiere global biotech leader. First, apitegromab regulatory approvals, and following those approvals, the US launch of apitegromab for children and adults with SMA, followed by a series of country launches in the coming years, starting in Europe with Germany next year.

謝謝，維卡斯。最後，我們致力於成功執行這些關鍵優先事項，這將使我們能夠將 Scholar Rock 轉變為全球首屈一指的生物技術領導者。首先，apitegromab 獲得監管部門批准，隨後，美國將推出用於治療 SMA 兒童和成人的 apitegromab，隨後幾年將在一系列國家推出，首先是明年在歐洲的德國。

Second, expand apitegromab into additional rare, severe, and debilitating neuromuscular diseases; and finally, disciplined capital allocation to support our high value commercial and development initiatives. On behalf of every member of the Scholar Rock team, I want to emphasize our unwavering commitment to more than 35,000 patients and their families.

其次，將 apitegromab 擴展到其他罕見、嚴重和使人衰弱的神經肌肉疾病；最後，進行嚴格的資本配置，以支持我們高價值的商業和發展計劃。我謹代表 Scholar Rock 團隊的每一位成員強調我們對 35,000 多名患者及其家人的堅定承諾。

Our mission is to move with urgency to ensure that no patient with SMA is left behind. With that, we'll now open the line for questions. Operator?

我們的使命是採取緊急行動，確保不落下任何一位 SMA 患者。現在，我們將開放提問熱線。操作員？

(Operator Instructions) Eric Schmidt, Cantor.

（操作員指令）埃里克·施密特，康托爾。

I appreciate the transparency around your CDMO issues. Can you tell us a little bit more about the specific observation at those two sites, whether you expect that a reinspection is going to be required prior to apitegromab approval and whether the two facilities right now are currently able to release other pharmaceutical products?

我很欣賞你們在 CDMO 問題上的透明度。您能否向我們詳細介紹這兩個地點的具體觀察情況，您是否預計在批准 Apitegromab 之前需要重新檢查，以及這兩個設施目前是否能夠發布其他藥品？

Yeah, thanks very much, Eric, and it's great to be working with you. First, I think as you know, Eric, GMP inspections are super standard as part of the FDA review process. And in fact, in 2024, based on FDA's inspection data dashboard, actually, more than 70% of drug quality assurance inspections resulted in observations noted by the FDA.

是的，非常感謝，艾瑞克，很高興能和你一起工作。首先，我認為正如你所知，Eric，GMP 檢查作為 FDA 審查流程的一部分是極其標準的。事實上，根據 FDA 的檢查數據儀表板，2024 年，超過 70% 的藥品品質保證檢查都引起了 FDA 的關注。

So as I noted in the call, we -- look, we're disappointed, but we weren't surprised to learn that two of our sites received observations. I think the benefit for us is those observations were presented well within our review cycle that allow for a response and obviously, a green light.

因此，正如我在電話中提到的那樣，我們 - 看起來，我們很失望，但我們並不驚訝地得知我們的兩個站點收到了觀察。我認為對我們有利的是，這些觀察結果在我們的審查週期內得到很好的呈現，從而可以做出回應，顯然，可以獲得綠燈。

It's always like very difficult to sort of read the tea leaves and try to understand what the FDA with those observations may want to do. Would they want a reinspection or not? At this moment in time, given the very constructive late cycle meeting that again was held after these site inspections and after these observations were provided, again, the tone and tenor and collaborative nature of that late cycle meeting certainly indicated to us that the agency is very much working toward completing their review of our BLA by the September 22 PDUFA date.

總是很難讀懂茶葉中的成分，也很難理解 FDA 根據這些觀察想要做什麼。他們是否想重新檢查？此時此刻，鑑於在這些現場檢查和提供這些意見之後再次舉行的非常建設性的後期週期會議，該後期週期會議的基調和基調以及協作性質再次向我們表明，該機構正在非常努力地在 9 月 22 日 PDUFA 日期之前完成對我們的 BLA 的審查。

I would also just note that we're obviously working on multiple levels with our CDMO partners. We're a skilled team, we're an experienced team. We understand how best to work through situations like this, which we are prepared to do.

我還要指出的是，我們顯然正在與 CDMO 合作夥伴進行多層次的合作。我們是一支技術嫻熟、經驗豐富的團隊。我們知道如何最好地解決這種情況，並且我們已經準備好了。

And David, do you know whether the two facilities are releasing any product currently?

大衛，您知道這兩個工廠目前是否正在發布任何產品嗎？

Very good question. The two facilities continue to operate, of course, the one that -- given the disclosure on August 1, it's not common practice in the industry, nor our common practice to name facilities, but in the case of Catalent, Indiana, now owned and operated by Novo Nordisk.

非常好的問題。當然，這兩家工廠仍在繼續運營，鑑於 8 月 1 日的披露，給工廠命名並不是行業慣例，也不是我們的慣例，但就印第安納州 Catalent 而言，現在由 Novo Nordisk 擁有和運營。

Certainly as you know Eric, that's an important filler across the board for a number of very important products across the industry and we know they continue to be very active, and the other facility continues to manufacture products as well. I think I would also note, and I think this is probably important for our entire audience, our supply chain has produced the apitegromab drug supply that has now accumulated over 600 patient years of experience through multiple years of clinical trials, including our pivotal trial, and the most recent EMBRAZE trial.

當然，正如你所知，埃里克，這是整個行業中許多非常重要的產品的重要填充物，我們知道他們繼續非常活躍，其他工廠也繼續生產產品。我想我還要指出的是，我認為這對我們所有觀眾來說可能都很重要，我們的供應鏈已經生產了 apitegromab 藥物，透過多年的臨床試驗，包括我們的關鍵試驗和最近的 EMBRAZE 試驗，現在已經積累了超過 600 名患者年的經驗。

And I think importantly, I'd like to note that our launch supply and beyond is manufactured, wild, and ready to go.

我認為重要的是，我想指出的是，我們的發射供應及其他供應已經製造完畢、準備就緒並投入使用。

Thank you very much.

非常感謝。

Allison Bratzel, Piper Sandler

艾莉森‧布拉澤爾，派珀‧桑德勒

Thanks for taking the questions. First, could you just further characterize any interactions with FDA, I mean, apitegromab review, outside of the observations that CDMOs you just discussed, any feedback on your overall confidence in receiving a broad label would be particularly helpful.

感謝您回答這些問題。首先，您能否進一步描述與 FDA 的任何互動，我的意思是，除了您剛才討論的 CDMO 的觀察結果之外，apitegromab 審查，任何關於您對獲得廣泛標籤的總體信心的反饋都將特別有幫助。

And then I think you talked about expansion of payer outreach. So could you just frame for us how your discussions with US payers are going and just overall receptiveness to coverage of apitegromab on top of SMN-targeting therapy.

然後我想您談到了擴大付款人範圍。那麼，您能否向我們簡單介紹一下您與美國付款人的討論進展如何，以及在 SMN 靶向治療的基礎上對 Apitegromab 的總體接受程度。

Yeah, no, thanks, Allison, and yes, as we noted, we were very encouraged by our late cycle meeting that we recently had, and Akshay can provide a little bit more context on that. And then as I noted, and Keith did as well, he's just recently deployed a sensational team and he can comment on some of those payer interactions related to the label and the interactions with the FDA. Akshay?

是的，不，謝謝，艾莉森，是的，正如我們所指出的，我們對最近舉行的後期週期會議感到非常鼓舞，阿克沙伊可以提供更多有關這方面的背景信息。然後，正如我和 Keith 所指出的，他最近剛剛部署了一支出色的團隊，他可以對與標籤相關的一些付款人互動以及與 FDA 的互動發表評論。阿克謝？

Yeah, thanks, David. We had an exceptionally constructive late cycle meeting recently with the FDA, all the different disciplines that needed to be there were there. We talked through the different aspects of the BLA. I think we were very pleased with the feedback we had. And so, we're working with them, as David said in his prepared statement towards September 22, and look forward to the rest of the BLA review being completed and we appear to be doing just that right now.

是的，謝謝，大衛。我們最近與 FDA 進行了一次非常有建設性的後期週期會議，所有需要參加的不同學科的人員都出席了會議。我們討論了 BLA 的不同面向。我認為我們對收到的回饋感到非常滿意。因此，正如戴維在 9 月 22 日的準備好的聲明中所說的那樣，我們正在與他們合作，並期待 BLA 審查的其餘部分能夠完成，而我們現在似乎正在這樣做。

Yeah, Allison, and as far as the payers, as you -- as we've noted before, we have a fully staffed payer team. Our outreach has been progressing to be able to be ready for our September 22 PDUFA date. The meetings have been going positive as we've been going through some of the apitegromab data and overall response, but importantly, the durability of response is something that payers have found quite impressive.

是的，艾莉森，就付款人而言，正如你之前提到的，我們有一個人員齊全的付款人團隊。我們的外展工作一直在進行，以便為 9 月 22 日的 PDUFA 日期做好準備。會議進展順利，因為我們一直在研究一些 apitegromab 數據和整體反應，但重要的是，反應的持久性是付款人非常印象深刻的。

Lastly, to your other question about paying for another therapy for SMA, I would say that you already have better than 20% of patients that are receiving more than one SMA therapy that is being paid for by payers at this time. So although the question has come up, the unmet medical need is there, and therefore all I can say is that discussions are going positive.

最後，關於您關於支付 SMA 另一種療法費用的另一個問題，我想說，目前已經有超過 20% 的患者正在接受一種以上的 SMA 療法，這些療法的費用由付款人支付。因此，儘管問題已經出現，但未滿足的醫療需求仍然存在，因此我只能說討論正在取得積極進展。

Thank you.

謝謝。

David Nierengarten, Wedbush Securities.

大衛‧尼倫加滕 (David Nierengarten)，韋德布希證券公司 (Wedbush Securities)。

Thanks for taking the questions. I just had -- it's one on the labeling, have you had labeling discussions with FDA and able to discuss possible labels with payers or is that to be discussed with the PDUFA date or as we approach the date.

感謝您回答這些問題。我剛剛問了——這是關於標籤的問題，您是否與 FDA 討論過標籤問題，並且能夠與付款人討論可能的標籤，或者是否要與 PDUFA 日期或接近該日期時進行討論。

And then the second one is if there is unfortunately a delay in the PDUFA, does that possibly put the PRV at risk, if there are different changes in the budget that starts on October 1, the fiscal year.

然後第二個問題是，如果不幸出現 PDUFA 延遲，如果從 10 月 1 日開始的財政年度的預算發生不同的變化，這是否會使 PRV 面臨風險。

Yeah, maybe I'll take that second or last question, David. First, there would be no change in PRV and I think you've all come to know us, this group of management team, we're we think about everything. We're a measured twice, cut once, type of crowd, and we would think through any scenarios even before. As we mentioned, we weren't totally surprised by observations only because three quarters of the time they happen.

是的，也許我會回答第二個或最後一個問題，大衛。首先，PRV 不會有任何變化，我想大家都已經了解我們，這群管理團隊，我們會考慮一切。我們是那種三思而後行的人，我們會事先考慮所有可能發生的情況。正如我們所提到的，我們對觀察結果並不完全感到驚訝，因為四分之三的時間它們都會發生。

And so we would have been thinking through all of this and there'd be no impact on the PRV at all, which is important and very good news. Regarding just the constructive nature of the dialogue and the label, I'll have Akshay common.

因此，我們會仔細考慮所有這些因素，而這些因素根本不會對 PRV 產生影響，這是非常重要且非常好的消息。就對話和標籤的建設性而言，我會讓 Akshay 變得常見。

Yeah, so with respect to that topic, again, we had a very good late cycle meeting and as you can expect at the late cycle meeting all the different aspects of the BLA leading to the potential approval are discussed, including labeling and the timings around who can expect what. We've had those types of interactions. I can't get into more details than that right now, but we were reassured that everyone is working towards September 22.

是的，關於這個主題，我們再次舉行了一次非常好的後期週期會議，正如你所預料的那樣，在後期週期會議上，我們將討論 BLA 獲得潛在批准的所有不同方面，包括標籤和誰可以期待什麼的時間。我們有過這類互動。我現在無法透露更多細節，但我們確信每個人都在為 9 月 22 日的目標而努力。

Great. Thank you.

偉大的。謝謝。

Tessa Romero, JPMorgan.

摩根大通的 Tessa Romero。

So just double clicking back on some of the earlier comments you've made, what is the right way to think about the next step following these observations given proximity to your goal date and how likely do you think that the outcome of the review will be positive in light of these findings and remain on time?

因此，只需雙擊您之前所做的一些評論，考慮到距離目標日期的接近程度，根據這些觀察結果，如何正確思考下一步？根據這些發現，您認為審查結果有多大可能是正面的，並且會準時完成？

And then my second question is what does an ideal label look like for apitegromab and at this point, what do you believe the indication statement should be?

我的第二個問題是，apitegromab 的理想標籤是什麼樣的，目前，您認為適應症說明應該是什麼？

Thank you, Tess. Great questions. So just kind of letting you into our kitchen a little bit, what you might expect us to be doing is working very closely with our CDMO partners. So in other words, like being well aware of the observations, having input on the responses to those observations, and then having levels of transparency both with the CDMOs and their communication with the agency, as well as our own continued dialogue with the agency through the final stages of our review process.

謝謝你，苔絲。很好的問題。因此，只是讓您稍微了解一下我們的廚房，您可能希望我們做的是與我們的 CDMO 合作夥伴密切合作。換句話說，就像充分了解觀察結果、對這些觀察結果的回應提供意見、然後與 CDMO 及其與該機構的溝通保持一定程度的透明度，以及在審查過程的最後階段我們自己與該機構的持續對話。

And so I would just say that, we have substantial talent internally. We would always take a no stone left unturned approach to external experts to help us and help our CDMO partners think through the very best way to respond observations. As I noted, we're confident that Novo submitted, and we actually have access to those responses that they made earlier this week. And the same will hold true for the responses that are going in within the week related to the other CDMO.

所以我只想說，我們內部擁有大量人才。我們始終會不遺餘力地尋求外部專家的幫助，並幫助我們的 CDMO 合作夥伴思考應對觀察的最佳方法。正如我所指出的，我們相信 Novo 已經提交了申請，而且我們實際上可以看到他們本週早些時候做出的回應。對於一周內收到的與其他 CDMO 相關的回复，情況也是如此。

So we'll have a great visibility into this and then multiple lines of communication through our CDMO partners as well as the FDA directly. Related to the ideal label, I'd turn it over to Akshay and Keith, that one of the things we've worked very hard on by taking a no shortcut approach to the development program is the robustness of our Phase 2 and then Phase 3 trial.

因此，我們將對此有很好的了解，然後透過我們的 CDMO 合作夥伴以及 FDA 直接進行多個溝通管道。關於理想的標籤，我想把它交給 Akshay 和 Keith，我們採取不走捷徑的開發計劃而努力工作的事情之一就是我們的第 2 階段和第 3 階段試驗的穩健性。

And so obviously, when we think about children and adults with SMA, we think about aligning with our partners at Cure SMA, really for the best interests of the community, a broad label is quite important so that all patients who can benefit from apitegromab will have access to apitegromab.

因此，顯然，當我們考慮患有 SMA 的兒童和成人時，我們會考慮與 Cure SMA 的合作夥伴保持一致，真正為了社區的最大利益，廣泛的標籤非常重要，以便所有可以從 apitegromab 中受益的患者都能獲得 apitegromab。

For more comments on the label, I'll hand it over to Akshay.

有關標籤的更多評論，我將把它交給 Akshay。

Yeah, thanks, David. So with respect to that topic, [Kappa] itself studied individuals 2 years and older to the age of 21. The primary endpoint was for the group that was 2 to 12 year old. We obviously hit that primary endpoint. We relayed the data again today. The important thing is that the data in the 13 to 21 were also entirely consistent with what we saw in the 2 to 12 group. And so, I think we can expect that those on the 2 that were not studied may not be in the label, but certainly above 2, we would like to see those in the label, given the very exciting findings from SAPPHIRE, all the way up into adulthood.

是的，謝謝，大衛。因此，就該主題而言，[Kappa] 本身研究了 2 歲及以上至 21 歲的個體。主要終點是 2 至 12 歲的族群。我們顯然達到了那個主要終點。今天我們再次轉發了資料。重要的是，13 至 21 歲組的數據也與我們在 2 至 12 歲組看到的數據完全一致。因此，我認為我們可以預期，那些未經研究的 2 歲以下兒童可能不會出現在標籤中，但肯定的是，考慮到 SAPPHIRE 的令人興奮的發現，我們希望在標籤中看到那些 2 歲以上的兒童，一直到成年期。

And if a patient in SAPPHIRE is 21 years old and is experiencing benefit, they're not going to suddenly stop getting benefit when they're 22. So I think, from a logic perspective, 2 years and older is a way to think about the group that would be eligible. But again, we cannot give any final information on that until the FDA has finished their deliberations. But --

如果 SAPPHIRE 中的患者 21 歲並且正在享受福利，那麼他們不會在 22 歲時突然停止享受福利。因此，我認為，從邏輯角度來看，2 歲及以上是考慮符合條件的群體的一種方式。但同樣，在 FDA 完成審議之前，我們無法提供任何最終資訊。但--

And one last thing I'd come on in our very strong partnership with CurSMA, they've actually advocated with the FDA for many years, the importance of sometimes a narrower clinical trial, but a broader label, recognizing the biology of the disease isn't necessarily different as patients get older.

最後我想說的是，我們與 CurSMA 建立了非常牢固的合作關係，他們實際上多年來一直向 FDA 倡導有時進行更窄的臨床試驗但使用更廣泛的標籤的重要性，認識到疾病的生物學特性並不一定會隨著患者年齡的增長而改變。

We were gratified that our most recent study in adults, over 100 adults showed the biology of myostatin again held up. That of course was with the EMBRAZE trial, but it has been common practice that there can be a slightly narrower patient population in a pivotal trial, but then in acceptance of a broader label, and that's what we're working toward. The ideal label, as Akshay said, would be the patients at 2 years of age and older would have access to the therapy.

我們感到欣慰的是，我們最近對超過 100 名成年人進行的研究再次證明了肌肉生長抑制素的生物學特性。這當然是在 EMBRAZE 試驗中，但通常的做法是，在關鍵試驗中患者群體可能會稍微縮小一些，但隨後會接受更廣泛的標籤，這就是我們正在努力的方向。正如 Akshay 所說，理想的標籤是 2 歲及以上的患者可以接受治療。

Thank you.

謝謝。

Marc Frahm, TD Cowen.

馬克‧弗拉姆 (Marc Frahm)，TD Cowen。

Thanks for taking my questions. First, can you push a little bit on the pricing discussion that you're having with payers. Just, I think we are encouraged that 20%-plus of patients are getting clinical combination therapy today, even without Phase 3 data supporting that. But maybe the ask on the payers is a little bit different with that, right? Because most of that is one-time gene therapy costs that may have already occurred and then on an annual budget basis just one therapy, just -- can you talk through how they're kind of thinking through the budget impact of maybe two SMA type pricing drugs in individual patients happening on a concurrent and ongoing basis.

感謝您回答我的問題。首先，您能否稍微談談與付款人進行的定價討論。只是，我認為，即使沒有 3 期數據支持，今天仍有 20% 以上的患者接受臨床聯合治療，這讓我們感到鼓舞。但也許對付款人的要求有點不同，對嗎？因為其中大部分是一次性基因治療費用，可能已經發生，然後在年度預算基礎上僅進行一種治療，只是 - 您能否談談他們如何考慮兩種 SMA 類型定價藥物同時並持續發生在個別患者身上對預算的影響。

And then maybe from the R&D side, starting a new indication later this year, should we view that as like one pilot outside of SMA or is that just the first of many we should expect as we go into '26, additional indications to continue to be added to the pipeline.

然後也許從研發方面來看，今年稍後開始一項新的適應症，我們是否應該將其視為 SMA 之外的試點，或者這只是我們進入 26 年後應該期待的眾多試點中的第一個，其他適應症將繼續添加到管道中。

Marc, thanks, very thoughtful questions. On the pricing side, I would note, of course, as I have in the past, that we'll consider a number of things when establishing the price. Certainly the rarity of SMA and you talk about budget impact as an individual patient, we obviously think about just how rare SMA is.

馬克，謝謝，這個問題非常有想法。在定價方面，我當然要指出，就像我過去一樣，我們在確定價格時會考慮很多因素。當然，SMA 很罕見，而且您談到對個別患者的預算影響，我們顯然會考慮 SMA 有多罕見。

The severity of the disease despite the use of over the past 10 years of SMN-targeted therapies where they have shown in some of their long-term data and we then again underscored in our Phase 3 trial that patients eventually moved to a progressive state of motor function loss, and how severe SMA is despite the use of best-known standard of care.

儘管過去 10 年來一直使用 SMN 標靶療法，但病情仍然嚴重，一些長期數據顯示，患者最終會進入進行性運動功能喪失狀態，我們在第 3 階段試驗中再次強調，儘管使用了最著名的標準治療方法，SMA 仍然很嚴重。

And then of course the compelling clinical benefits that we can provide and some of those were underscored by Akshay earlier. And so, we'll think about those things, we'll think about the budget impact. And one of the things we also have a lot of experience with this looking at even sort of pricing corridors for rare disease therapies, monotherapies in different settings and sort of thinking about sort of where the starting point is today.

當然，我們可以提供令人信服的臨床益處，其中一些 Akshay 之前已經強調過了。因此，我們會考慮這些事情，我們會考慮預算的影響。我們在這方面也擁有豐富的經驗，我們甚至研究過罕見疾病治療的定價區間、不同環境下的單一療法，並思考過今天的起點在哪裡。

We definitely do not think the air is then, in terms of payers of willingness to support both physician interest as well as patient interest and accessing and people comment in a moment on the importance of dual modality therapy for this devastating disorder. Keith?

我們絕對不認為付款人願意同時支持醫生的利益和患者的利益，並且人們會立即評論雙重治療對這種毀滅性疾病的重要性。基思？

Yeah, thanks, David. Marc, one of the things is -- you mentioned that this is -- using two agents who's just post (inaudible), and I just want to call out that we actually have met with patients and physicians that have tried both (inaudible) and spinraza simultaneous, so they're paying for two current agents at the same time.

是的，謝謝，大衛。馬克，其中一件事是 - 你提到這是 - 使用兩種剛發布的藥物（聽不清楚），我只想說，我們實際上已經見過同時嘗試過（聽不清）和 spinraza 的患者和醫生，所以他們同時支付兩種現有藥物的費用。

So it's not just post gene therapy. The bottom line is that over time, these patients on these SMN-targeted therapies, many of them plateau and then they begin to decline, and payers are realizing that there is a great deal of unmet medical need that's left.

所以它不僅僅是基因治療後。最重要的是，隨著時間的推移，在這些接受 SMN 標靶治療的患者中，許多患者的病情會達到穩定狀態，然後開始惡化，而付款人意識到還有大量未滿足的醫療需求。

If I think about the fact, as David mentioned, treating with dual modality and targeting the muscle directly as well as the motor neuron, it gives you an opportunity to potentially not only increase your response as we've shown from the SAPPHIRE data, but then also have a durability of response over time. And so that is a meaningful impact that is valuable to payers.

如果我考慮到這個事實，正如大衛提到的那樣，採用雙重模式治療並直接針對肌肉和運動神經元，它不僅給你一個機會來潛在地增加你的反應，正如我們從 SAPPHIRE 數據中顯示的那樣，而且還可以隨著時間的推移保持反應的持久性。因此，這對付款人來說是一個有意義的、有價值的影響。

And then Marc, regarding the other sort of a pipeline and a product strategy that Akshay is so skillfully leading, I'll have him comment.

然後，馬克，關於阿克沙伊如此巧妙地領導的另一種管道和產品策略，我會請他發表評論。

Yeah, thanks, Marc. So we see enormous opportunities for antagonizing myostatin in a whole array of neuromuscular disorders. And so, yes, there will be many opportunities that you'll see us studying. We'll begin with one by the end of the year, but I think it will add that in quick succession over time. So much more to come on that.

是的，謝謝，馬克。因此，我們看到了在一系列神經肌肉疾病中拮抗肌肉生長抑制素的巨大機會。所以，是的，你會看到我們有很多學習的機會。我們將在今年年底開始推出一款，但我認為隨著時間的推移，我們會陸續推出其他產品。關於這一點，還有更多內容。

Okay, thank you.

好的，謝謝。

Martin Auster, Raymond James.

馬丁奧斯特、雷蒙詹姆斯。

This is Thomas on for Marty. Thanks for taking our question. Maybe just went on the OPAL trial here. Anything you can say about expected enrollment timelines there, and maybe just frame for us how to think about the significance of that expansion opportunity if we envision an initial label for apitegromab in patients 2 years and older.

這是托馬斯代替馬蒂上場。感謝您回答我們的問題。也許只是在這裡參加了 OPAL 試驗。能否透露一下預期的招募時間表？如果我們設想為 2 歲及以上的患者提供 apitegromab 的初始標籤，您可以為我們闡述如何看待這一擴展機會的重要性。

Yeah, thank you very much, and consistent with our ambition and mission of the company that no patient would ever be left behind, including babies and toddlers, this is an important study for us and as Akshay noted, so I'll have him comment a little bit further on the study and expected timelines.

是的，非常感謝，這與我們公司的抱負和使命一致，即不會拋棄任何患者，包括嬰兒和幼兒，這對我們來說是一項重要的研究，正如 Akshay 所說，所以我會讓他進一步評論一下這項研究和預期的時間表。

Yeah, thanks. So with respect to timelines, we're going to start enrollment in Q3 as I said on the prepared remarks. My usual practice is let's get that going and then in the coming quarter or two as we see momentum build, we'll be able to guide further on the exact completion date of the study.

是的，謝謝。因此，就時間表而言，正如我在準備好的發言中所說的那樣，我們將在第三季開始招生。我通常的做法是先開始，然後在接下來的一兩個季度裡，隨著勢頭的增強，我們將能夠進一步指導研究的具體完成日期。

And with respect to 0 to 2 year old children with SMA and the label, we didn't study under the age of 2 in the SAPPHIRE study. We've initiated this study to understand the impact of the drug in that population safety PK/PD efficacy. And as David said, no child should be left behind with this disease, and we think apitegromab can have an impact across the entire age range here.

而關於0至2歲SMA兒童及標籤，我們在SAPPHIRE研究中並沒有研究2歲以下的患童。我們發起這項研究是為了了解該藥物對人群安全 PK/PD 功效的影響。正如大衛所說，任何孩子都不應該被拋棄，因為患有這種疾病，我們認為 apitegromab 可以對整個年齡層的人產生影響。

I think in terms of trying to do good with this drug and helping as many kids as possible, one thing I would know is that the prevalent population is much, much larger than the insulin population. And so the 0 to 2 are the new children being born with SMA, that's dwarfed by the 35,000 or greater who currently have SMA are on treatments, and we believe could be helped by a drug like apitegromab.

我認為，就嘗試利用這種藥物做好事並幫助盡可能多的孩子而言，我知道的一件事是，患病人群比胰島素人群要多得多。因此，0 至 2 名新生兒患有 SMA，與目前接受治療的 35,000 名或更多 SMA 患者相比，這個數字相形見絀，我們相信像 apitegromab 這樣的藥物可以對他們有所幫助。

So there's a lot for us to do whilst we get OPAL done and start helping under 2, and we'll begin with 2 years and older.

因此，在完成 OPAL 並開始幫助 2 歲以下兒童的同時，我們還有很多工作要做，我們將從 2 歲及以上的兒童開始。

Thank you.

謝謝。

Srikripa Devarakonda, Truist Securities.

Sriripa Devarakonda，Truist 證券公司。

Thank you so much for taking my question. I just want to go back to the CDMO site inspections. Now, if there is a need for another inspection, do you have a sense of timelines as to when you will get to know that by? And now, given the CRLs that we've seen with one of the peers involved, what are typical timelines for potential resolution of these issues?

非常感謝您回答我的問題。我只是想回到 CDMO 現場檢查。現在，如果需要進行另一次檢查，您是否知道何時可以知道？現在，考慮到我們在其中一個同行那裡看到的 CRL，解決這些問題的潛在時間表通常是什麼？

Yeah, thanks, Kripa. Again, it's hard to predict what the FDA will do. I mean, I think -- you all do this for a living, and as do we, and the best we can do like you, is assess what has happened from time to time in the industry and what could be some of the different scenarios, but I can tell you that from all of our experience and that of our expert advisors that we are working with along with our CDMOs, the very best thing to do initially is have a robust response to those observations, and that is what we've been spending a lot of time on.

是的，謝謝，克里帕。再一次，很難預測 FDA 會採取什麼行動。我的意思是，我認為——你們都以此為生，我們也是，我們能做的最好的事情就是評估行業中不時發生的事情以及可能出現的一些不同情況，但我可以告訴你們，根據我們所有的經驗以及我們與 CDMO 合作的專家顧問的經驗，最初最好的事情就是對這些觀察結果做出強有力的回應，這就是我們花費大量時間去做的事情。

The robustness of those of those responses obviously can have an impact on whether or not any reinspection would be required. And so that's where our effort is being placed and then again, I think -- as I noted, we would be gathering information both through our CDMO partners but then also directly with the review division and we'll keep you apprised at that.

這些回應的穩健性顯然會影響是否需要重新檢視。這就是我們努力的方向，而且我認為——正如我所指出的，我們將透過我們的 CDMO 合作夥伴收集信息，同時也直接與審查部門收集信息，我們會隨時向您通報情況。

But right now, given the fact that following these site inspections and following the presentation of those observations, we held our late cycle meeting. The FDA completed that late cycle meeting. The dialogue, the tone, the content of the discussion was very encouraging, with a commitment to move forward toward our PDUFA date under priority review of September 22, and we will certainly keep you and all of our stakeholders apprised on that progress.

但現在，考慮到這些現場檢查和這些觀察結果的提出，我們召開了後期週期會議。FDA 完成了此後期週期會議。對話、基調和討論內容都非常令人鼓舞，我們承諾在 9 月 22 日的優先審查下繼續推進我們的 PDUFA 日期，我們一定會讓您和所有利益相關者了解這一進展。

Great. Thank you so much.

偉大的。太感謝了。

Evan Seigerman, BMO Capital Markets.

埃文·塞格曼 (Evan Seigerman)，BMO 資本市場。

I have two questions for me. Can you provide more color characterize the interactions from your late cycle review meetings. Today, it all talked about just the difference in efficacy we saw between the 20 milligram and the 10 milligram doses and also the cost one for you, if we think about kind of modeling, the asset post launch, how should we think about the cadence in the back half of this year and into next year?

我有兩個問題。您能否提供更多細節來描述後期週期審查會議的互動。今天，我們討論的只是 20 毫克劑量和 10 毫克劑量之間的功效差異，以及成本差異，如果我們考慮建模類型、資產發布後，我們應該如何考慮今年下半年和明年的節奏？

Yeah, Evan, great question. Regarding the combined dose analysis, I'll have Akshay comment on that, which obviously, as you know, there's been extensive clinical work done with the [10 m] and 20 most recently EMBRAZE was 10. Akshay?

是的，埃文，這個問題問得好。關於聯合劑量分析，我將讓 Akshay 對此發表評論，顯然，如您所知，已經對 [10 m] 和 20 進行了廣泛的臨床研究，最近的 EMBRAZE 是 10。阿克謝？

Yeah, so the life cycle interaction was indeed very constructive and positive. So we have discussed the file fully including the combined dose analysis with all of you before, and we've had a very constructive discussions with regulators around that as well. As you know, we hit the primary endpoint. The important thing is both 10 and 20 have an almost identical dynamic effect, and so it's unsurprising that both showed a positive outcome with efficacy.

是的，所以生命週期互動確實非常有建設性和積極性。因此，我們之前已經與大家全面討論過該文件，包括聯合劑量分析，我們也就此與監管機構進行了非常建設性的討論。如您所知，我們達到了主要終點。重要的是，10 和 20 都具有幾乎相同的動態效果，因此兩者都顯示出積極的療效也就不足為奇了。

And combining the two groups increased statistical power to be able to see the difference versus placebo and obviously we saw gain in most function with apitegromab versus the decline. And our expectation is that given that the regulatory practice is to approve the lowest dose that's efficacious and given that both have equivalent pharmacodynamic impact. We would request that 10 milligram per kilogram is the approved dose. I'll leave it that.

將兩組結合起來可以提高統計能力，能夠看到與安慰劑相比的差異，顯然，我們看到使用 apitegromab 後大多數功能都有所提高，而使用安慰劑後則有所下降。我們的期望是，鑑於監管實踐是批准有效的最低劑量，並且兩者俱有相同的藥效學影響。我們要求每公斤 10 毫克作為核准劑量。我就不說了。

And on the financial side, we still to do the 2026 budget planning session, but as I mentioned in my call, I'm going to be very thoughtful about how we go into the next year. Some of the expenses in the clinical side is going to drop out next year and then we'll replace it with the prioritization as Akshay was laying out in his section with moving 439 and some of the pipeline forward.

在財務方面，我們仍需進行 2026 年預算規劃會議，但正如我在電話中提到的那樣，我將非常認真地考慮如何進入明年。臨床方面的一些費用明年將會取消，然後我們將按照 Akshay 在其部門中列出的優先順序來代替，推動 439 和一些管道向前發展。

So that's other indications for us. So that's our key priority in keeping our overall spending in check. We do expect it to be in similar lines like what we spent this year.

這對我們來說是其他跡象。因此，這是我們控制整體支出的首要任務。我們確實希望它與我們今年的支出類似。

Thank you, ladies and gentlemen. This concludes the Q&A session and concludes today's call. Thank you all for joining. You may now disconnect.

謝謝各位，女士們、先生們。問答環節到此結束，今天的電話會議也結束了。感謝大家的加入。您現在可以斷開連線。