Insmed Inc (INSM) 2025 Q2 法說會逐字稿

Hello, and thank you for standing by. My name is Tiffany, and I will be your conference operator today. At this time, I would like to welcome everyone to the Insmed's second-quarter 2025 financial results conference call. (Operator Instructions)

您好，感謝您的支持。我叫蒂芬妮，今天我將擔任您的會議主持人。現在，我歡迎大家參加 Insmed 2025 年第二季財務業績電話會議。（操作員指示）

I would now like to turn the call over to Bryan Dunn, Head of Investor Relations. Bryan, please go ahead.

現在我想將電話轉給投資者關係主管布萊恩鄧恩 (Bryan Dunn)。布萊恩，請繼續。

Thank you, Tiffany. Good day, everyone, and welcome to today's conference call, in which we will discuss Insmed's second-quarter 2025 financial results and provide an update on our business. Before we start, please note that today's call will include forward-looking statements based on our current expectations.

謝謝你，蒂芙尼。大家好，歡迎參加今天的電話會議，我們將討論 Insmed 2025 年第二季的財務業績並提供我們業務的最新情況。在我們開始之前，請注意，今天的電話會議將包括基於我們當前預期的前瞻性陳述。

These statements represent our judgment as of today, and inherently involve risks and uncertainties that may cause actual results to differ materially from the projections discussed. Please refer to our filings with the Securities and Exchange Commission for more information.

這些聲明代表了我們今天的判斷，並且本身涉及風險和不確定性，可能導致實際結果與討論的預測有重大差異。請參閱我們向美國證券交易委員會提交的文件以了解更多資訊。

The information we will discuss on today's call is meant for the benefit of the investment community. It is not intended for promotional purposes, and it is not sufficient for prescribing decisions. Today's call will feature prepared comments by Will Lewis, Chair and Chief Executive Officer; Roger Adsett, Chief Operating Officer; and Sara Bonstein, Chief Financial Officer. After their comments, they will be joined by Martina Flammer, Chief Medical Officer, for the Q&A session.

我們在今天的電話會議上討論的資訊是為了投資界的利益。它不用於促銷目的，也不足以規定決策。今天的電話會議將由董事長兼首席執行官威爾·劉易斯 (Will Lewis)、首席營運官羅傑·阿德塞特 (Roger Adsett) 和首席財務官薩拉·邦斯坦 (Sara Bonstein) 發表準備好的評論。在他們發表評論後，首席醫療官 Martina Flammer 將加入他們的問答環節。

I will now turn the call over to Will.

現在我將把電話轉給威爾。

Thank you, Bryan, and welcome, everyone. As I reflect on the first half of 2025, I'm enormously pleased with where Insmed stands as a company and the potential impact we can have on the lives of the patients we serve.

謝謝你，布萊恩，歡迎大家。回顧 2025 年上半年，我對 Insmed 公司的發展現狀以及我們可能對所服務患者的生活產生的影響感到非常滿意。

Insmed is now three for three, all three of our late-stage assets, ARIKAYCE, brensocatib, and TPIP, appear to be clear winners with positive Phase 2 or Phase 3 clinical data having been produced by each, which is an extraordinary achievement for any company in this industry.

Insmed 現在是三連勝，我們所有三個後期資產 ARIKAYCE、brensocatib 和 TPIP 似乎都是明顯的贏家，每個資產都產生了積極的第 2 階段或第 3 階段臨床數據，這對於該行業的任何公司來說都是一項非凡的成就。

These successes have been made possible by the work we put in over the last 18 months across every aspect of our business, including commercial execution, pre-commercial launch readiness, regulatory interactions, clinical development activities, early-stage research, and enabling functions. I could not be prouder of our teams of dedicated colleagues at Insmed.

這些成功得益於我們過去 18 個月在業務各個方面所做的努力，包括商業執行、商業發布前準備、監管互動、臨床開發活動、早期研究和支援功能。我為 Insmed 敬業的同事團隊感到無比自豪。

As a result of this impressive operational performance and our solid financial position, flowing both from the performance of ARIKAYCE and our recent capital raise, we feel Insmed is in an incredible position of strength. I want to emphasize that this is just the beginning. The next 12 months for Insmed are shaping up to be extraordinarily impactful.

由於這一令人印象深刻的營運業績和我們穩固的財務狀況，源於 ARIKAYCE 的業績和我們最近的資本籌集，我們認為 Insmed 處於令人難以置信的優勢地位。我想強調的是，這只是一個開始。對於 Insmed 來說，未來 12 個月將會產生極其深遠的影響。

We expect a steady cadence of meaningful events, both commercially and clinically, that have the potential to significantly expand the company's impact on patients and establish Insmed's next wave of products and indications that will drive future growth. If successful, these catalysts could enable us to address more than 2 million patients with serious diseases across multiple products and indications in the coming years.

我們預計，無論是商業上還是臨床上，一系列有意義的事件都將穩步發生，這些事件有可能顯著擴大公司對患者的影響，並確定 Insmed 的下一波產品和適應症，從而推動未來的成長。如果成功的話，這些催化劑可以讓我們在未來幾年內透過多種產品和適應症治療超過 200 萬名患有嚴重疾病的患者。

To summarize the progress Insmed has made and highlight what still lies ahead, I'd like to divide our discussion into two sections: our late-stage portfolio and our early-stage portfolio. Our late-stage portfolio is made up of ARIKAYCE, brensocatib, and TPIP.

為了總結 Insmed 的進展並強調未來的發展方向，我想將我們的討論分為兩個部分：後期投資組合和早期投資組合。我們的後期投資組合由 ARIKAYCE、brensocatib 和 TPIP 組成。

ARIKAYCE continues to perform in its current indication, demonstrating consistent year-over-year growth in its seventh year of launch. We believe we are on track to achieve our full-year 2025 sales guidance, driven by continued growth in the US, Europe, and Japan. Our performance to date has been particularly impressive given that our US sales team has been simultaneously conducting disease state education on bronchiectasis.

ARIKAYCE 繼續在當前適應症下表現良好，在推出的第七年呈現出持續的同比增長。我們相信，在美國、歐洲和日本持續成長的推動下，我們預計將實現 2025 年全年銷售目標。鑑於我們的美國銷售團隊一直在同時進行支氣管擴張症的疾病狀態教育，我們迄今為止的表現尤其令人印象深刻。

In the first half of 2026, we anticipate the clinical readout of the Phase 3 ENCORE study in patients with newly diagnosed or recurrent MAC lung disease, who have not started antibiotics. If ENCORE is successful, as ARISE was, approximately 225,000 additional patients could gain access to ARIKAYCE, driving another leg of growth for the franchise.

我們預計在 2026 年上半年對尚未開始使用抗生素的新診斷或復發性 MAC 肺病患者進行 3 期 ENCORE 研究的臨床讀數。如果 ENCORE 能夠像 ARISE 一樣取得成功，那麼大約有 225,000 名額外的患者可以獲得 ARIKAYCE 的服務，從而推動該特許經營權的另一個增長階段。

Moving now to brensocatib, we are days away from potentially launching the first indication for brensocatib in the US, representing one of the most anticipated launches in our industry this year. Launches for brensocatib in non-cystic fibrosis bronchiectasis in Europe, the UK, and Japan are expected in 2026.

現在談談 brensocatib，我們距離在美國推出 brensocatib 的第一個適應症只有幾天的時間了，這是今年我們行業中最受期待的上市產品之一。預計 2026 年，歐洲、英國和日本將推出用於治療非囊性纖維化支氣管擴張症的 brensocatib。

We also expect top-line data from our BiRCh study of brensocatib in patients with CRS without nasal polyps by the end of 2025 and the interim futility analysis for our CEDAR study of brensocatib in patients with hidradenitis suppurativa in the first quarter of 2026. As we've indicated before, if successful, these studies could unlock a massive opportunity for brensocatib to potentially serve other large patient populations with very few treatment options.

我們也預計，到 2025 年底，我們將獲得針對無鼻息肉的慢性鼻竇炎患者使用 brensocatib 的 BiRCh 研究的頂線數據，並在 2026 年第一季度獲得針對化膿性汗腺炎患者使用 brensocatib 的 CEDAR 研究的中期無效性分析。正如我們之前指出的，如果成功，這些研究將為 brensocatib 帶來巨大的機會，使其有可能服務於其他治療選擇很少的龐大患者群體。

Lastly, TPIP. We have now produced positive results for TPIP in two Phase 2 studies. We anticipate entering Phase 3 for PH-ILD in 2025 and for PAH in early 2026. We believe TPIP has the potential to become the prostanoid of choice for the treatment of PAH and PH-ILD, pending positive results in these Phase 3 programs.

最後，TPIP。目前，我們在兩項第 2 階段研究中已取得 TPIP 的正面成果。我們預計將於 2025 年進入 PH-ILD 的第 3 階段，並於 2026 年初進入 PAH 的第 3 階段。我們相信，只要這些 3 期計畫取得正面成果，TPIP 就有潛力成為治療 P​​AH 和 PH-ILD 的首選前列腺素。

Turning now to our early-stage portfolio, this portfolio is made up of our gene therapy operation in San Diego; our de-immunized therapeutic protein operation in New Hampshire; our synthetic rescue research efforts in Cambridge, England; and our research work happening in our original labs based in New Jersey.

現在談談我們的早期投資組合，該投資組合由我們在聖地亞哥的基因治療業務、我們在新罕布什爾州的去免疫治療蛋白業務、我們在英國劍橋的合成救援研究工作以及我們在新澤西州的原始實驗室進行的研究工作組成。

Across all four of these operations, we have more than 30 preclinical programs in active development. We've historically highlighted that our preclinical research efforts are expected to stay below 20% of our overall spend, with the goal of producing one to two new INDs a year on average. To that end, the last several years have produced significant progress.

在這四個業務中，我們有超過 30 個臨床前專案正在積極開發中。我們一直強調，我們的臨床前研究工作預計將保持在總支出的 20% 以下，目標是平均每年產生一到兩個新的 IND。為此，過去幾年我們取得了重大進展。

Our San Diego research site, which was acquired four years ago, has published encouraging preclinical data in DMD, ALS, and Stargardt disease, with the latter representing the first application of our proprietary RNA end-joining technology. This research site recently initiated its first Phase 1 study in patients with DMD, with additional INDs expected in the coming years.

我們四年前收購的聖地牙哥研究基地已經發布了 DMD、ALS 和 Stargardt 病的令人鼓舞的臨床前數據，其中後者代表了我們專有的 RNA 末端連接技術的首次應用。該研究基地最近啟動了針對 DMD 患者的首個 1 期研究，預計未來幾年將進行更多 IND。

Our New Hampshire research site, which has been part of Insmed since early 2021, has produced exciting progress as well with its AI-based protein de-immunization platform, demonstrating promising results in preclinical models, setting up the possibility for de-immunized proteins to potentially address a variety of conditions, initially looking at uricase and IgG protease.

我們的新罕布夏州研究基地自 2021 年初以來一直是 Insmed 的一部分，其基於 AI 的蛋白質去免疫平台也取得了令人興奮的進展，在臨床前模型中展示了有希望的結果，為去免疫蛋白質潛在地解決各種情況奠定了可能性，最初研究的是尿酸酶和 IgG 蛋白酶。

Our Cambridge, England, site, which we acquired in 2023, continues to make steady progress on identifying targets for its synthetic rescue platform to potentially be employed against some of the world's most difficult-to-treat diseases, such as ataxia-telangiectasia. More recently, they have also advanced a potential treatment in ALS using a different approach from the SOD1 gene therapy being developed by our San Diego team.

我們於 2023 年收購的位於英國劍橋的工廠在確定其合成救援平台的目標方面繼續取得穩步進展，該平台有可能用於治療世界上一些最難治療的疾病，例如共濟失調毛細血管擴張症。最近，他們也採用了與我們聖地牙哥團隊正在開發的 SOD1 基因療法不同的方法，推進了 ALS 的潛在治療方法。

Finally, our original New Jersey-based research site continues to be a hub of innovation for Insmed. Not only were ARIKAYCE and TPIP produced from these labs, but they have also screened approximately 850 potential next-generation DPP1 inhibitors and are currently conducting pre-IND work for the first of these molecules that we hope will enter the clinic next year.

最後，我們最初位於新澤西的研究基地繼續成為 Insmed 的創新中心。這些實驗室不僅生產了 ARIKAYCE 和 TPIP，而且還篩選了大約 850 種潛在的下一代 DPP1 抑制劑，目前正在為這些分子中的第一個進行 IND 前工作，我們希望這些分子能夠在明年進入臨床階段。

Consistent with Insmed's core values, a spirit of collaboration and mutual support exists between these sites. They are overseen by a research council, which is comprised of two representatives from each location.

與 Insmed 的核心價值一致，這些站點之間存在著合作和相互支持的精神。它們受到一個研究委員會的監督，該委員會由來自每個地方的兩名代表組成。

The council and select members from each of these research sites gather in person twice each year to provide progress updates, offer input, and explore ways to collaborate to potentially accelerate the development process. But there's a lot going on in our early-research engine. We will only provide regular updates on the programs that have cleared the IND hurdle.

該委員會和來自每個研究站點的選定成員每年聚會兩次，提供進展更新、提供意見並探索合作方式以潛在地加速開發進程。但我們的早期研究引擎還有很多事情要做。我們將僅定期更新已通過 IND 障礙的項目。

In general, we continue to see meaningful progress across each of our early-stage research platforms and are excited for what is to come. As one example of the progress being made, last month, our first patient with DMD was dosed with INS1201, our investigational intrathecally delivered gene therapy, as part of our Phase 1 ASCEND study.

總的來說，我們繼續看到每個早期研究平台都取得了有意義的進展，並對未來感到興奮。作為正在取得進展的一個例子，上個月，作為我們第一階段 ASCEND 研究的一部分，我們的第一位 DMD 患者接受了 INS1201（我們正在研究的鞘內注射基因療法）。

Moreover, we anticipate multiple INDs coming from our early-stage research engine over the next year, including our gene therapies for ALS and Stargardt disease, as well as our next generation of DPP1 inhibitors. In addition to the advancement of our internal research efforts, targeted business development remains a priority.

此外，我們預計明年我們的早期研究引擎將推出多個 IND，包括針對 ALS 和 Stargardt 病的基因療法，以及我們的下一代 DPP1 抑制劑。除了推進內部研究工作外，有針對性的業務發展仍然是我們的首要任務。

As always, we will aim to advance the best opportunities that are aligned with our strategy of bringing first and best-in-class therapies to patients facing serious diseases. With this architecture in mind, it is my hope that you can appreciate Insmed's significant progress while visualizing the exciting future ahead for both our late-stage and early-stage portfolios.

像往常一樣，我們將致力於推動符合我們策略的最佳機會，為面臨嚴重疾病的患者提供一流和最佳的治療方法。考慮到這種架構，我希望您能夠欣賞 Insmed 的重大進步，同時展望我們後期和早期投資組合令人興奮的未來。

Let's now take a few moments to walk through some updates from our late-stage programs, starting with brensocatib. The US launch of brensocatib in bronchiectasis is arguably the most important catalyst for us to get right in the near term.

現在讓我們花點時間來了解我們後期專案的一些更新，首先是 brensocatib。美國推出用於治療支氣管擴張症的 brensocatib 可以說是我們近期進展的最重要催化劑。

I'm pleased to report that we have submitted our agreement to the FDA about our label. And from our perspective, we remain on track for a decision on or before the PDUFA target action date next week.

我很高興地報告，我們已經向 FDA 提交了有關我們標籤的協議。從我們的角度來看，我們仍有望在下週的 PDUFA 目標行動日期或之前做出決定。

Given how close we are to launch, I've asked Roger, our Chief Operating Officer and former Chief Commercial Officer, to share some of his own thoughts on how our launch preparations compare to those he has seen throughout his distinguished career.

鑑於我們即將推出新產品，我請我們的首席營運長兼前首席商務官羅傑分享一些他自己的想法，比較一下我們的發布準備工作與他傑出職業生涯中所見過的發布準備工作。

Let me now turn it over to Roger.

現在讓我把它交給羅傑。

Thank you, Will. Good morning, everyone. It's a pleasure to be with you this morning. As I reflect on the resources invested in the preparation for brensocatib US launch, it's apparent to me that the team is well positioned to execute on this opportunity. A few things in particular stick out to me.

謝謝你，威爾。大家早安。我很高興今天早上能和你們在一起。當我回顧為 brensocatib 美國上市準備所投入的資源時，我發現團隊已經做好了充分的準備來抓住這個機會。有幾件事特別讓我印象深刻。

First, I've never seen a company prepare its customer-facing organization so far in advance of the launch. As we've shared previously, we had our sales force fully built out, trained, and in the field more than 10 months ahead of time.

首先，我從未見過一家公司在產品發布前如此提前做好面向客戶的準備。正如我們之前所分享的，我們的銷售團隊提前 10 個多月就已全面組建、培訓完畢並投入使用。

Many companies wait until approval to deploy these resources or elect to do so only a handful of months in advance. Our proactive decision to expand our commercial organization in this way is one that, I believe, will result in more patients gaining access to this important therapy and more physicians feeling prepared to prescribe it.

許多公司等到獲得批准後才部署這些資源，或選擇僅提前幾個月部署。我相信，我們主動決定以這種方式擴大我們的商業組織，將使更多的患者能夠獲得這種重要的治療方法，並使更多的醫生願意開立這種藥物。

Second, I often see companies overlook the importance of developing resources that support the experience of patients and prescribers. If attaining access proves too burdensome for patients or physicians' offices to navigate, providers may hesitate to prescribe and patients may fail to fill their scripts.

其次，我經常看到公司忽略開發支持患者和處方者體驗的資源的重要性。如果獲得藥物對患者或醫生辦公室來說太繁重，那麼醫療服務提供者可能會猶豫是否開處方，而患者也可能無法按時取藥。

It's for this reason that Insmed significantly built out its patient support function called inLighten, which is fully deployed and ready to assist patients and physicians to navigate the complexities of the healthcare system from day one. Additionally, while it's common for companies to conduct outreach with payers ahead of new product launches, payer feedback in our early discussions about brensocatib has been particularly supportive of our approach.

正是出於這個原因，Insmed 大力發展了名為 inLighten 的患者支援功能，該功能已全面部署，可以從第一天起就隨時幫助患者和醫生應對複雜的醫療保健系統。此外，雖然公司在新產品發布前與付款人接觸是很常見的，但在我們早期關於 brensocatib 的討論中，付款人的回饋特別支持我們的方法。

The importance of patient access can at times be underestimated in determining a launch's success, particularly when our product is entering a market with no clear competition. I'm pleased that our team has taken nothing for granted on that front. Our prioritization of patient access acknowledges its critical aspect of successful launches and fully aligns with our patient-focused culture.

在決定產品發布成功與否時，患者獲取的重要性有時會被低估，尤其是當我們的產品進入一個沒有明顯競爭的市場時。我很高興我們的團隊在這方面沒有掉以輕心。我們優先考慮患者的就診，承認其對於成功啟動至關重要，並且完全符合我們以患者為中心的文化。

Finally, I want to mention our current understanding of physician enthusiasm headed into this launch. Based on our interactions with key opinion leaders and our extensive survey work, it is clear to us that physicians have a very high intent to prescribe brensocatib to appropriate patients.

最後，我想提一下我們目前對醫生對此次發表會的熱情的理解。根據我們與關鍵意見領袖的互動以及廣泛的調查工作，我們清楚地看到，醫生非常願意為合適的患者開出布倫索卡蒂布。

And while we know the surveyed physicians often assume they will write more scripts than they actually will in practice, the fact that 90% of surveyed physicians indicate that they indicate to prescribe -- intend to prescribe brensocatib to their patients with two more pulmonary exacerbations over the last 12 months, is extremely encouraging.

雖然我們知道受訪的醫生通常認為他們開出的處方比實際開出的處方要多，但 90% 的受訪醫生表示，他們打算為過去 12 個月內肺部症狀加重兩次以上的患者開出布倫索卡提布，這一事實非常令人鼓舞。

Now as with every launch, not everything will go to plan. And while there's no way to fully anticipate what challenges may arise, I see our brensocatib team is being prepared to respond to whatever may come. They are equipped with a culture in which raising your hand at the first sign of a problem is championed. And they are nimble enough to make necessary adjustments quickly.

現在，就像每次發射一樣，並不是所有的事情都會按計劃進行。雖然我們無法完全預測可能出現的挑戰，但我看到我們的 brensocatib 團隊正在準備好應對可能出現的任何挑戰。他們擁有這樣一種文化：一發現問題就立即採取行動。而且他們夠靈活，能夠迅速做出必要的調整。

I also want to remind you that even the best of launches can take weeks from approval to get medicines into the hands of patients. This is primarily due to the time it takes to print final labels and packaging, guide the product through distribution channels, and navigate patient access. As a result, for brensocatib, you should continue to expect only a few weeks of sales for the third quarter, assuming approval by our PDUFA date next week.

我還想提醒大家，即使是最好的藥物，從批准到將藥物送到患者手中也可能需要數週時間。這主要是因為列印最終標籤和包裝、引導產品通過分銷管道以及引導患者訪問需要時間。因此，對於 brensocatib，假設我們下週的 PDUFA 日期之前批准，您應該繼續預計第三季只有幾週的銷售量。

Having said that, let me emphasize again that everything I've seen from this team's preparation and brensocatib's unique profile leads me to believe that this medicine has the potential to have one of the best launches in the specialty respiratory space.

話雖如此，讓我再次強調，從這個團隊的準備工作和 brensocatib 的獨特特性來看，我所看到的一切讓我相信這種藥物有可能成為專業呼吸領域最好的藥物之一。

Now let me turn it back to Will.

現在讓我把話題轉回給威爾。

Thanks for sharing those insights, Roger. I want to stay with brensocatib, but move to its second potential indication, CRS without nasal polyps.

感謝您分享這些見解，羅傑。我想繼續使用 brensocatib，但轉向它的第二個潛在適應症，即不伴隨鼻息肉的慢性鼻竇炎 (CRS)。

As we mentioned on our last call, the Phase 2 BiRCh study was fully enrolled in April and continues to steadily advance towards its completion. Encouragingly, the Data Safety Monitoring Committee held its second meeting last month to review blinded safety information. The committee found no safety signals and unanimously recommended that the study continue unmodified.

正如我們在上次電話會議上提到的，第二階段 BiRCh 研究已於 4 月全面招募，並繼續穩步推進直至完成。令人鼓舞的是，資料安全監測委員會上個月召開了第二次會議，審查了盲法安全資訊。委員會沒有發現任何安全訊號，並一致建議繼續進行研究，不做任何修改。

This represents the best possible outcome from this meeting. Recall that the BiRCh trial is testing 10- and 40-milligram doses of brensocatib which is different from the 10- and 25-milligram doses that were studied in our bronchiectasis trials. So it is reassuring that there are no safety signals that have emerged even at a higher dose.

這是本次會議可能取得的最佳成果。回想一下，BiRCh 試驗正在測試 10 毫克和 40 毫克劑量的 brensocatib，這與我們在支氣管擴張試驗中研究的 10 毫克和 25 毫克劑量不同。因此，令人放心的是，即使劑量較高，也沒有出現安全訊號。

While we continue to expect the data from the BiRCh trial to become available before the end of the year, the exact timing of the top-line readout is still being determined, given our usual practice of taking whatever time is necessary to ensure the data are clean to submission-level quality. We remain eager to see those data and look forward to what those results could mean for patients.

雖然我們仍然預計 BiRCh 試驗的數據將在年底前公佈，但考慮到我們通常的做法是花一切必要時間來確保數據乾淨且達到提交級別的質量，頂線讀數的確切時間仍有待確定。我們仍然渴望看到這些數據，並期待這些結果對患者意味著什麼。

Our Phase 2 CEDAR study in patients with hidradenitis suppurativa is also progressing nicely, with more than 50% of the target enrollment completed. Given the strong enrollment to date, we now expect to be in a position to share the outcome of the interim futility analysis of the first 100 patients in the first quarter of next year.

我們針對化膿性汗腺炎患者進行的 2 期 CEDAR 研究也進展順利，目標入組人數已完成 50% 以上。鑑於迄今為止的入組人數眾多，我們現在預計將能夠在明年第一季分享前 100 名患者的中期無效性分析結果。

These two follow-on programs for brensocatib hold the potential to establish DPP1 inhibition as a mechanism that can offer benefits to patients across multiple neutrophil-mediated diseases. Success in either of these indications would add to our confidence both in brensocatib and in the likelihood that our next-generation DPP1 molecules could also serve patients with a variety of other conditions.

這兩個針對 brensocatib 的後續項目有可能將 DPP1 抑制確立為一種機制，為多種中性粒細胞介導疾病的患者帶來益處。上述任何一種適應症的成功都會增強我們對 brensocatib 的信心，也增強我們對下一代 DPP1 分子也能為患有其他多種疾病的患者提供服務的可能性的信心。

Turning now to our TPIP program, the clinical highlight of Insmed's second quarter was the top-line data release from our Phase 2b trial of TPIP in patients with pulmonary arterial hypertension. The results exceeded even our most optimistic expectations and established, in our view, the potential for TPIP to become the prostanoid of choice in the treatment of PAH.

現在談談我們的 TPIP 計劃，Insmed 第二季度的臨床亮點是我們對肺動脈高壓患者進行的 TPIP 2b 期試驗的頂線數據發布。結果甚至超出了我們最樂觀的預期，在我們看來，TPIP 有可能成為治療 P​​AH 的首選前列腺素。

To recap those results, the 35% placebo-adjusted reduction in PVR represented the largest treatment effect ever shown in a well-controlled trial, of which we are aware. Additionally, the 35.5-meter placebo-adjusted improvement in six-minute walk distance produced a p-value well below 0.05, which, despite not being adjusted for multiplicity, was especially striking because the trial was not powered to show a statistical outcome on this measure.

總結這些結果，經安慰劑調整後，PVR 降低了 35%，這是我們所知的一項嚴格控制的試驗中顯示的最大治療效果。此外，經安慰劑調整後，六分鐘步行距離改善 35.5 米，其 p 值遠低於 0.05，儘管沒有進行多重性調整，但這一結果仍然特別引人注目，因為該試驗無法顯示該指標的統計結果。

Even more impressive was the fact that these endpoints were measured approximately 24 hours after the latest dose, demonstrating the sustained clinical benefit of the treatment over a 24-hour timeframe. With these data, our focus now turns to our Phase 3 ambitions. We have made significant strides on that front and are on track to kick off the Phase 3 in PH-ILD in the second half of this year.

更令人印象深刻的是，這些終點是在最後一次服藥後約 24 小時測量的，證明了該治療在 24 小時內持續的臨床益處。有了這些數據，我們現在將重點轉向第三階段的目標。我們在這方面取得了重大進展，並預計在今年下半年啟動 PH-ILD 第三階段。

The work we have done to update the capsule strengths so that doses up to 600 micrograms can be delivered in a single capsule, is now complete. And we have engaged with regulators on our plans for trial design, which will allow for dosing up to a maximum of 1,280 micrograms. We look forward to sharing the details of the PH-ILD Phase 3 trial design later this year.

我們所做的更新膠囊強度的工作現已完成，以便單一膠囊可以提供高達 600 微克的劑量。我們已經與監管機構就試驗設計計劃進行了溝通，該計劃允許的最大劑量為 1,280 微克。我們期待在今年稍後分享 PH-ILD 第三階段試驗設計的細節。

In addition, our program in PAH is also advancing on schedule. With our final clinical study report of the Phase 2 trial now complete, we can approach the agency for a meeting to discuss those results and align on a Phase 3 trial design that will meet the regulator's expectations for approval. We expect that meeting to take place in October, setting up the potential Phase 3 start in early 2026.

此外，我們在PAH的專案也按計劃推進。隨著我們第二階段試驗的最終臨床研究報告的完成，我們可以與該機構聯繫開會討論這些結果，並確定符合監管機構批准期望的第三階段試驗設計。我們預計會議將於 10 月舉行，為 2026 年初啟動第三階段做好準備。

Let me conclude my remarks by saying that Insmed is ready. We have been preparing for years to execute on the enormous clinical and commercial opportunities that lie ahead of us over the next 12 months. If we achieve this, we hope to produce a real and profound difference in the lives of patients living with serious diseases, while also potentially creating value for those who have supported us in our evolution to this position.

最後，我想說，Insmed 已經準備好了。多年來，我們一直在為未來 12 個月內面臨的巨大臨床和商業機會做準備。如果我們實現了這一目標，我們希望能夠為身患嚴重疾病的患者的生活帶來真正而深刻的變化，同時也可能為那些在我們發展到這一階段的過程中支持我們的人創造價值。

Central to our ability to achieve these ambitions is a culture that supports and empowers our people to do their best work. That is why I'm so proud that Insmed was recently certified as a Great Place To Work for the fifth year in a row. This is an incredible honor, and it is reflective of how our employees feel about working at Insmed.

我們實現這些目標的核心是一種支持和鼓勵員工盡最大努力工作的文化。這就是為什麼我為 Insmed 最近連續第五年被認證為「最佳工作場所」而感到自豪。這是一個令人難以置信的榮譽，它反映了我們的員工對在 Insmed 工作的感受。

Our people are responsible for all of our successes to date. And similarly, our people will be the ones who will determine our future. This recognition serves as external validation of what I see internally every day, that the special culture we have built at Insmed is being preserved even as our team expands. As a company, we have never been stronger or more motivated to deliver on our mission.

我們迄今為止的所有成功都歸功於我們的員工。同樣，我們的人民也將決定我們的未來。這種認可是對我每天在內部所見所聞的外部驗證，即，即使我們的團隊不斷擴大，我們在 Insmed 建立的特殊文化仍得以保留。作為一家公司，我們從未像現在這樣強大和有動力去完成我們的使命。

I'll now turn the call over to Sara.

我現在將電話轉給薩拉。

Thank you, Will, and good morning, everyone. Let me begin my discussion of second-quarter 2025 results by highlighting the strong commercial performance of ARIKAYCE, which is illustrated here on slide 16. In what may be our final quarter as a single-product company, we were pleased to once again deliver double-digit year-over-year revenue growth globally.

謝謝你，威爾，大家早安。在討論 2025 年第二季業績時，我首先要強調的是 ARIKAYCE 強勁的商業表現，如投影片 16 所示。作為一家單一產品公司，這可能是我們的最後一個季度，但我們很高興再次在全球範圍內實現了兩位數的同比增長。

These impressive results were driven by the highest quarterly revenue figure ever achieved in the United States, along with yet another quarter of extremely impressive performances in both Japan and Europe, all of which was driven by strong volume trends.

這些令人印象深刻的業績得益於美國有史以來最高的季度收入數字，以及日本和歐洲又一個季度極其令人印象深刻的業績，所有這些都是由強勁的銷售趨勢推動的。

In Japan, the 45% growth this quarter resulted from the implementation of new targeting strategies and initiatives to improve the patient experience. For Europe, the 48% growth was driven primarily by strong demand in Germany, Switzerland, and Austria.

在日本，本季 45% 的成長得益於實施新的目標策略和措施以改善患者體驗。對歐洲而言，48% 的成長主要得益於德國、瑞士和奧地利的強勁需求。

Due to the strength of this performance, we remain on track to achieve our 2025 full-year ARIKAYCE net revenue guidance of $405 million to $425 million. As a reminder, this guidance range is specific to ARIKAYCE only and does not include any future revenue contributions from brensocatib, if approved.

由於業績強勁，我們仍有望實現 2025 年全年 ARIKAYCE 淨收入預期 4.05 億美元至 4.25 億美元。提醒一下，此指導範圍僅適用於 ARIKAYCE，不包括 brensocatib（如果獲得批准）的任何未來收入貢獻。

On slide 17, you can see our updated cash balance as of the end of the quarter. This reflects the equity offering that was completed in the second quarter and includes the exercise in full of the underwriter's option to purchase additional shares, which, in total, resulted in the sale of approximately 9 million shares of our common stock at $96 per share, resulting in approximately $823 million in net proceeds to the company.

在第 17 張投影片上，您可以看到截至本季末的最新現金餘額。這反映了第二季完成的股票發行，包括承銷商購買額外股份的選擇權的全面行使，總共以每股 96 美元的價格出售了約 900 萬股普通股，為公司帶來了約 8.23 億美元的淨收益。

At approximately $1.9 billion in cash, cash equivalents, and marketable securities as of the end of the quarter, we believe we are extremely well capitalized. Excluding option exercises and proceeds from our recent equity offering, our underlying cash burn for the quarter was consistent with the underlying burn levels that we have seen for the past several quarters, which is remarkable given the additional investments we've made in launch preparations over that period.

截至本季末，我們持有約 19 億美元的現金、現金等價物和有價證券，我們相信我們的資本非常充足。不包括選擇權行使和我們最近股票發行的收益，我們本季的基本現金消耗與過去幾季的基本現金消耗水準一致，考慮到我們在此期間在發布準備工作中所做的額外投資，這是非常了不起的。

Although we don't guide to cash burn levels, in general, we expect our burn will begin to decrease in the coming quarters, as the expected revenue growth from brensocatib's US launch has the potential to more than offset the expected increases in spending.

雖然我們沒有對現金消耗水準進行指導，但總體而言，我們預計未來幾季我們的現金消耗將開始減少，因為 brensocatib 在美國上市帶來的預期收入成長有可能超過預期的支出成長。

Moving to slide 18, you can see our operating expenses for the quarter. Cost of product revenues in the second quarter of 2025 was $28.1 million or 26.1% of revenues, which is slightly higher on a percentage basis than our historical performance and reflects the higher proportionate of revenues, which came from outside the US this quarter.

移至第 18 張投影片，您可以看到我們本季的營運費用。2025 年第二季的產品收入成本為 2,810 萬美元，佔營收的 26.1%，按百分比計算略高於我們的歷史業績，反映了本季來自美國以外地區的收入比例較高。

Additionally, research and development and SG&A expenses increased this quarter compared to the prior- year period. This increase was primarily driven by investments supporting our commercial readiness initiatives ahead of the expected US launch of brensocatib, enhancements in our international commercial operations, and continued funding across our early- and late-stage pipelines.

此外，本季研發及銷售、一般及行政費用與去年同期相比有所增加。這一增長主要得益於我們在預期的美國推出 brensocatib 之前對商業準備計劃的支持投資、我們國際商業運營的增強以及對我們早期和後期研發管線的持續資助。

In closing, I want to comment briefly on where we are positioned financially as a company and what still lies ahead. We have had a remarkable run of clinical successes over the past 18 months that has transformed Insmed and given us one of the most exciting portfolios of commercial and late-stage assets in all of biotech.

最後，我想簡單評論一下我們公司的財務狀況以及未來的發展方向。在過去的 18 個月中，我們取得了一系列令人矚目的臨床成功，這不僅改變了 Insmed，也為我們帶來了整個生技領域最令人興奮的商業和後期資產組合之一。

Over the next 12 months, we anticipate up to 10 additional commercial, clinical development, and regulatory milestones, which we believe have the potential to create incremental value. With our recent equity financing, we believe we are well positioned to lean in and deliver on each of those catalysts.

在接下來的 12 個月裡，我們預計將有多達 10 個額外的商業、臨床開發和監管里程碑，我們相信這些里程碑有可能創造增量價值。透過最近的股權融資，我們相信我們已做好準備，充分利用每一個催化劑。

While we never give guidance on our expected cash runway or timing for achieving profitability for purposes of maintaining financial flexibility, I can say without hesitation that Insmed is in the best financial position in its history. We remain committed to thoughtfully and efficiently deploying our capital to maximize the opportunities ahead of us on behalf of patients.

雖然為了保持財務靈活性，我們從未對預期現金流量或實現盈利的時間做出指導，但我可以毫不猶豫地說，Insmed 正處於其歷史上最好的財務狀況。我們始終致力於周到而有效地部署我們的資本，以最大限度地為患者創造機會。

We would now like to open the call to questions. Operator, may we take the first question, please?

我們現在開始提問。接線員，我們可以回答第一個問題嗎？

(Operator Instructions) Jason Zemansky, Bank of America.

（操作員指示）美國銀行 Jason Zemansky。

Good morning. Congrats on the progress and really appreciate you taking our question. In conversations with investors of late, there have been some questions over the patient journey given that NCFB and brenso is a new indication.

早安.恭喜您的進展，非常感謝您回答我們的問題。最近在與投資者的對話中，由於 NCFB 和 brenso 是一個新的適應症，因此對患者的治療歷程提出了一些問題。

So ahead of next week, I was hoping you could provide some color into what you're doing on a practical level to capture patients. Obviously, interest from the stakeholders are a huge positive. But what are some of the mechanics you're doing to practically move a patient onto treatment?

因此，在下週之前，我希望您能夠提供一些關於您在實際層面上為吸引患者所做的事情的詳細資訊。顯然，利害關係人的興趣是一個巨大的利好。但是，您實際上採取了哪些措施來讓患者接受治療呢？

What are some of the key systems you put in place? And ultimately, what gives you confidence the team can succeed, again, given the challenges that this is essentially a new market that you're building on your own? Thanks.

您實施了哪些關鍵系統？最後，考慮到這本質上是一個您獨自打造的新市場所面臨的挑戰，是什麼讓您對團隊能夠成功充滿信心？謝謝。

Yeah, I appreciate the question. I think the first thing to remember is that we've been here before. We did the same exact rollout with ARIKAYCE as the first-ever approved product for the treatment of refractory MAC lung disease.

是的，我很感謝你的提問。我認為首先要記住的是，我們以前來過這裡。我們對 ARIKAYCE 進行了完全相同的推廣，這是第一個獲準用於治療難治性 MAC 肺病的產品。

And just to remind everybody, because it's a point we like to remember and try to learn from and also celebrate, when we first came out with ARIKAYCE, I think the average estimate for revenue was $40 million to $60 million in the first year. And we ended up doing, I think, a little over $130 million, so triple what most people thought we were going to be able to accomplish.

只是為了提醒大家，因為這是我們想要記住、嘗試從中學習並慶祝的一點，當我們第一次推出 ARIKAYCE 時，我認為第一年的平均收入估計為 4000 萬至 6000 萬美元。我認為，我們最終籌集的資金略高於 1.3 億美元，是大多數人認為我們能夠完成的金額的三倍。

And I think there's always a reticence that -- taking on a new indication requires more effort, more work, and is more uncertain. But that's why we started as early as we did. And that's why we got our teams out into the field, as Roger mentioned, starting in October 1 of last year.

我認為人們總是持保留態度——接受新的適應症需要付出更多努力、做更多工作，而且更不確定。但這就是我們這麼早就開始的原因。正如羅傑所提到的，這就是我們從去年 10 月 1 日開始派遣團隊前往實地的原因。

So the first answer to your question, practically, is to get people out into the field to do disease state awareness and to build the relationships that enable physicians to reflect on if there is a new medicine that is approved. They know the patient profile that would respond, and they can have already thought about that.

因此，實際上，對你的問題的第一個回答是讓人們走進實地了解疾病狀況，並建立關係，讓醫生能夠思考是否有新藥獲得批准。他們知道會有反應的患者特徵，而且他們可能已經考慮過了。

And so I think we've heard from KOLs and actually community-level physicians that many of them have, if you will, a list of patients that they want to turn to, that they think are suitable for this right out of the gate. That information conforms to what we had seen in our research when we went out and sort of sized this market initially, which we've told you is roughly in the US about 500,000 patients that are diagnosed today with bronchiectasis and have an ICD-10 code and all the rest.

因此，我認為我們已經從關鍵意見領袖和社區醫生那裡聽說，他們中的許多人都有一份他們想要求助的患者名單，他們認為這些患者一開始就適合接受這種治療。這些資訊與我們最初進行研究並確定該市場規模時所看到的情況相符，我們告訴您，目前在美國大約有 500,000 名患者被診斷患有支氣管擴張症，並擁有 ICD-10 代碼等。

Of that, roughly half, we think, have had two or more exacerbations in the last 12 months. Down to the physician level, we have now profiled every physician in the United States. And we have information on their expected patient numbers, if you will.

其中，我們認為大約有一半的患者在過去 12 個月內曾病情加重過兩次或兩次以上。細化到醫生層面，我們現在已經對美國的每一位醫生進行了分析。如果您願意的話，我們也掌握了有關預計患者人數的資訊。

So I think we have a very good idea of where all these patients are and how to go about gaining access to them. We've been putting that in place since we kicked off our disease state awareness campaign literally two years ago at ATS.

所以我認為我們非常清楚這些病人在哪裡以及如何接觸他們。自從兩年前我們在 ATS 啟動疾病狀態意識運動以來，我們就一直在實施這項計畫。

More practically, as the patients come in, whether the physician calls them over the phone or needs to see them in person, either way, once that script recommendation and writing takes place, there's an entire front-end of the funnel that will grab the patient and make it available to them to join the inLighten program, that Roger made reference to, which is a patient support program, that will help guide them through that process in a compliant and appropriate way.

更實際的是，當患者進來時，無論醫生是通過電話聯繫他們還是需要親自見他們，無論哪種方式，一旦處方推薦和編寫完成，就會有一個完整的漏斗前端來吸引患者並讓他們加入 Roger 提到的 inLighten 計劃，這是一個患者支持計劃，它將幫助他們以合規和適當的方式完成整個過程。

And then there's also all the efforts that the specialty pharmacies will be prepared to make. We have, at a tactical level across the engagement with patients and physicians and the physicians' offices in a very compliant way, support systems available to ensure that this process is what we refer to as a frictionless launch.

此外，專業藥局也將做好充分準備，做出一切努力。在戰術層面上，我們以非常合規的方式與患者、醫生和醫生辦公室互動，並提供支援系統，以確保這一過程是我們所謂的無摩擦啟動。

And it's our hope that we'll be able to deliver on that. So I hope that gives you a little bit more insight. But I would say, out of the gate, we feel cautiously optimistic that we are ready to engage with this opportunity.

我們希望能夠實現這一目標。我希望這能帶給你更多的了解。但我想說，我們一開始就謹慎樂觀地認為我們已經準備好抓住這個機會。

And just one other piece I would just highlight, Jason, is the creation of the COPD Foundation and then creating the 150 care center networks around the United States. And as of last -- the first cohort, I believe, there was about 33 sites identified to be centers of excellence for both NTM and bronchiectasis. And sort of the next wave is going to be happening and be put into place very soon. So I think that is also another very tangible piece that's going to help on the patient journey side.

傑森，我還要強調的一點是創立 COPD 基金會，然後在美國各地建立 150 個護理中心網絡。截至去年，我相信第一批大約有 33 個站點被確定為 NTM 和支氣管擴張的卓越中心。下一波浪潮即將到來並很快到來。所以我認為這也是另一個非常切實的方面，將有助於患者的旅程。

Got it. So is there optimism you can capture these additional asthma COPD patients as well?

知道了。那麼，您是否有信心能夠治癒這些額外的氣喘 COPD 患者呢？

So I think at this stage, what we've said is we're initially targeting the patients we know that have been diagnosed. As disease state awareness efforts take hold, I think physicians will be asking the question, do I have more patients than I realize?

所以我認為在現階段，我們所說的是，我們最初的目標是那些我們知道已經被診斷出來的患者。隨著疾病狀態意識工作的開展，我認為醫生會問這樣的問題：我的病人是否比我意識到的要多？

And that's -- we like to say that if you have asthma or COPD and you're in max-dose available therapy and you're still experiencing exacerbations, that should trigger a question in the physician's mind as to perhaps there's something more going on with the patient. And with the CT scan, they can get the answer to that question.

那就是——我們想說的是，如果您患有氣喘或慢性阻塞性肺病，並且正在接受最大劑量的治療，但病情仍然惡化，那麼醫生應該會懷疑患者是否還有其他問題。透過 CT 掃描，他們可以得到這個問題的答案。

So we're encouraging that reflection so that physicians, when they think it's appropriate, will follow that path. And that would gain access to those patients who are comorbid with COPD or asthma, if those CT scans were to show definitively that they had bronchiectasis and had experienced two or more exacerbations in the last year.

因此，我們鼓勵這種反思，以便醫生在認為合適的時候遵循這條道路。如果 CT 掃描結果明確顯示患有支氣管擴張症，並且在過去一年中病情發作兩次或兩次以上，那麼就可以接觸到那些同時患有 COPD 或氣喘的患者。

If that is the patient profile, then they would be -- what we would expect to be on label, if things go as we expect they will, next week. And I think that is a big opportunity, right? We've -- as I said before, 500,000, half of which are two or more exacerbations that are identified right now. Behind that are multiples of that in size of potential patients, and we'll have to see how that unfolds. We'll be tracking that one very carefully.

如果這是患者的概況，那麼他們就會——我們期望在標籤上顯示的內容，如果事情按照我們預期的那樣發展，那麼下週就會出現。我認為這是一個很大的機會，對嗎？正如我之前所說，我們已經有 50 萬例，其中一半是目前已發現的兩次或兩次以上加重症狀。在這背後，潛在患者的數量是這個數字的數倍，我們將拭​​目以待。我們將非常仔細地跟踪這一點。

Great. Thanks for the color.

偉大的。謝謝你的顏色。

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

Hi, guys, thanks for taking the question. Mine is just a follow-up to the previous question. Well, you used an interesting phrase when you talked about payer feedback. You said that the feedback has been positive on the Insmed approach to these patients.

大家好，感謝你們回答這個問題。我的問題只是對上一個問題的後續。嗯，當您談到付款人回饋時，您使用了一個有趣的短語。您說 Insmed 對這些患者的治療方法得到了積極的回饋。

And it sounds like it is patients who have a CT diagnosis, who have documented two-plus exacerbations. Are there other aspects to that Insmed approach or Insmed profile that you can elaborate on? Like, for instance, do you have an idea at this point about what sort of prior authorizations outside diagnosis or two exacerbations might be?

聽起來，這些患者都有 CT 診斷，並且記錄了兩次以上的病情惡化。您能詳細說明一下 Insmed 方法或 Insmed 概況的其他方面嗎？例如，您現在是否知道診斷以外的事先授權或兩次加重的情況可能是什麼樣的？

But do you think there might be prescriber restrictions or like other diagnostic requirements outside CT to define that appropriate population? And can you also tell us if you plan on providing free drug with launch?

但是您是否認為可能會有處方限製或類似 CT 以外的其他診斷要求來定義適當的人群？您能否告訴我們您是否計劃在發佈時提供免費藥物？

Sure. So I'm actually going to ask Roger to address those questions.

當然。所以我其實要請羅傑來回答這些問題。

Yeah. Thanks, Ritu, for the question. I think what we anticipate -- and Will alluded to this as well -- is just a frictionless launch for brensocatib. And so as we think about that, that is to make the prior authorization process as smooth as possible, as easy as possible, for the physicians and the offices that actually usually the ones who process the paperwork and submit that.

是的。謝謝 Ritu 提出這個問題。我認為我們所預期的——威爾也提到了這一點——只是 brensocatib 的無摩擦發布。因此，當我們考慮這一點時，就是要讓事先授權流程盡可能順利、盡可能簡單，以便醫生和辦公室（通常是處理和提交文書工作的人）能夠順利完成。

And so as we engage with payers, we find some very strong alignment on thinking about the patients who are appropriate for using brensocatib. And so those are the patients with a bronchiectasis diagnosis through a CT scan. Our goal is to have an attestation for the physician that that's the case. That should be -- and I think that that's a very reasonable position that the payers are also understanding as a reasonable position.

因此，當我們與付款人接觸時，我們發現在考慮哪些患者適合使用 brensocatib 方面存在非常強烈的一致性。這些是透過 CT 掃描診斷為支氣管擴張的患者。我們的目標是讓醫生證明情況確實如此。那應該是——而且我認為這是一個非常合理的立場，付款人也理解為合理的立場。

And then the two more exacerbations over the past 12 months -- because that's the patient population that we studied in the clinical trials. And so we also think that that's an appropriate patient population. So there's a lot of alignment on that.

過去 12 個月內又出現了兩次病情惡化的情況——因為這是我們在臨床試驗中研究的患者群體。因此我們也認為這是一個合適的患者群。因此，在這方面有許多共識。

And so I think that part of the alignment is just -- this is a first-in-disease product and something that there's some excitement about, having a solution for these patients that are continuing to exacerbate. And so it's about aligning on the prior authorization and getting that criteria smooth as possible.

因此，我認為部分原因在於——這是一種首創的疾病產品，而且令人興奮，因為它為這些病情持續惡化的患者提供了解決方案。因此，這是為了與事先授權保持一致並儘可能順利地實現該標準。

And then the second question was around free product, I think it was. And so we aren't planning to do any sampling of brensocatib at this time. But we are making patient support available. We're helping with copays for the commercial patients, et cetera. And -- but no direct sampling to physicians.

我認為第二個問題是關於免費產品的。因此我們目前不打算對 brensocatib 進行任何採樣。但我們正在為患者提供支持。我們正在幫助商業患者支付共付額等等。並且——但沒有直接向醫生進行採樣。

Great. Thank you.

偉大的。謝謝。

Andrea Newkirk, Goldman Sachs.

高盛的安德里亞紐柯克 (Andrea Newkirk)。

Good morning. Thanks for taking the question. I'm looking forward to next week. Maybe I could ask you here with respect to TPIP, as you look to a competitor trial in IPF reading out next month, how are you thinking about the potential for treprostinil to demonstrate an antifibrotic effect there? And what could that then imply for TPIP?

早安.感謝您回答這個問題。我期待著下週。也許我可以在這裡問您關於 TPIP 的問題，當您期待下個月在 IPF 中讀出的競爭對手的試驗時，您如何看待曲前列尼爾在那裡表現出抗纖維化作用的潛力？那麼這對 TPIP 又意味著什麼呢？

And if that study were to be positive, can you just speak to how quickly you could move to advanced TPIP into an IPF study? Could you move directly to a Phase 3, or would some other dose finding work need to be completed first? Thanks so much.

如果這項研究是正面的，您能否說說您能多快將 TPIP 推進到 IPF 研究？您能直接進入第 3 階段嗎，還是需要先完成一些其他劑量探索工作？非常感謝。

Sure. I'm going to ask Martina to fill that.

當然。我要請 Martina 來填寫這個。

Yeah. Thanks for the question, Andrea. So with regards to the study, the TETON study that we anticipate reading out, certainly, we will look with great interest to this study, if we see positive results or even trends.

是的。謝謝你的提問，安德里亞。因此，關於這項研究，我們期待宣讀的 TETON 研究，如果我們看到積極的結果甚至趨勢，我們當然會非常感興趣地關注這項研究。

Given TPIP's profile, we would expect that we even have the opportunity to have stronger effects. And so we would be in a position to start off a Phase 3 study in a very short notice. But we all look forward to these results.

鑑於TPIP的概況，我們預期我們甚至有機會產生更強的影響。因此，我們可以在很短的時間內開始第三階段的研究。但我們都期待這些結果。

Jessica Fye, JPMorgan.

潔西卡費伊，摩根大通。

Hey, guys, good morning. Thanks for taking my question. So we're just around the corner from brenso's launch. And I wanted to revisit the analogs you provided a few quarters ago, where you looked at first-in-class, best-in-class respiratory launches.

嘿，大家早安。感謝您回答我的問題。因此，我們距離 Brenso 的發布僅一步之遙。我想重新審視您在幾個季度前提供的類似物，其中您研究了同類首創、同類最佳的呼吸系統產品發布。

I think at the time, you said those were analogs that any company would strive to even come close to. So I'm just curious, with all the preparation over the past year-plus, can you speak to your confidence in brenso achieving a ramp like that? Thank you.

我認為當時您說過，這些都是任何公司都會努力去接近的類似物。所以我很好奇，經過過去一年多的準備，您能否談談您對布倫索實現這樣的進步的信心？謝謝。

Sure. So while we're not providing formal guidance as to what we think we'll end up doing, I do have an ambition that we will fall within reach of those ranges. That's certainly what I would expect to hope to achieve. And the consequence of that would be what I think everyone would observe as a successful launch.

當然。因此，雖然我們沒有提供關於最終目標的正式指導，但我確實希望我們能夠達到這些範圍。這當然是我希望實現的目標。我認為，這樣做的結果就是每個人都會認為這是一次成功的發射。

We've done a lot to get ready. But as somebody observed earlier, this is a first-in-disease launch. And so there's always going to be something that goes bump in the night. And that may influence what we see in terms of performance. It's just impossible at this stage to give any greater clarity or know what the future will hold.

我們已經做了很多準備。但正如之前有人指出的那樣，這是首次針對該疾病的藥物上市。所以晚上總是會有一些意外發生。這可能會影響我們所看到的表現。目前，我們不可能給出更清晰的答案，也不可能知道未來會發生什麼事。

One of the things I did as preparation or grounding exercise is that I spoke to a lot of chief commercial officers at other companies that have been involved in launches recently. And almost to a person, they said that whatever their base case scenario was, their ultimate result was wildly off.

作為準備或基礎練習，我所做的事情之一是與最近參與發布的其他公司的許多首席商務官進行了交談。幾乎所有人都表示，無論他們的基本情況如何，最終結果都大不相同。

So it was either much higher or much lower, and I can tell you where I hope we end up. But certainly, we've done the preparation to accomplish that. But I think the key to that is making sure that we keep in mind the patient experience from day one.

所以它要么高得多，要么低得多，我可以告訴你我希望我們最終達到什麼水平。但可以肯定的是，我們已經做好了實現這一目標的準備。但我認為關鍵在於確保我們從第一天起就牢記患者的體驗。

We want the script to be written for the appropriate patient, of course, and support all that. But we really want the patient pull-through because we know that the drug from the Phase 3 trial and the Phase 2 trial make patients feel better.

當然，我們希望該腳本是為合適的患者編寫的，並支援所有這些。但我們確實希望患者能堅持下去，因為我們知道，第三階段和第二階段試驗的藥物會讓患者感覺更好。

And when we saw that data, we were encouraged by that. And we hope that that will be an experience that they have on the drug and that will reinforce the launch process. And I think not insubstantial amount of the future performance of the drug will be determined by that experience. So we look forward to be watching that carefully. It's just one example.

當我們看到這些數據時，我們受到了鼓舞。我們希望這將成為他們使用該藥物的一次經驗，並能加強藥物的上市。我認為，這種藥物的未來表現很大程度取決於這種經驗。因此我們期待仔細觀察這一點。這只是一個例子。

And just one other thing just to remind folks of -- as we saw with ARIKAYCE and with all products, it takes a couple of weeks from approval to when you actually start booking revenue. So assuming August 12, PDUFA data took about a month from approval of ARIKAYCE to when we actually started booking revenue. So just reminder to be mindful of that during projections.

還有一件事需要提醒大家——正如我們在 ARIKAYCE 和所有產品中看到的那樣，從批准到實際開始預訂收入需要幾週的時間。因此假設 8 月 12 日，PDUFA 資料從 ARIKAYCE 獲得批准到我們實際開始預訂收入大約需要一個月的時間。因此，提醒大家在預測期間要注意這一點。

Look, our ambition here and our preparation is for this to be a strong launch. And I'll be disappointed if we don't demonstrate that.

瞧，我們的目標和準備就是為了實現一次強勁的發布。如果我們做不到這一點，我會很失望。

Thank you.

謝謝。

Joe Schwartz, Leerink Partners.

Leerink Partners 的 Joe Schwartz。

Great. Thanks very much for taking my question. Since your reads on blended blinded data have been pretty accurate heading into past data sets, I wanted to ask if you could expand on the qualitative statements you've made about the BiRCh trial showing positive signs before you unblind it.

偉大的。非常感謝您回答我的問題。由於您對混合盲法資料的讀取在過去的資料集中非常準確，我想問您是否可以在揭盲之前擴展您對 BiRCh 試驗顯示出積極跡象的定性陳述。

Is there anything in particular that you're seeing in that data which makes you optimistic? And then on a related note, can you talk about what factors are included in your statement that you expect to unblind BiRCh this year, but reporting the data is dependent on taking whatever time is necessary to achieve submission-level quality? Is there anything in particular which could delay that readout?

您在這些數據中看到什麼特別的東西讓您感到樂觀嗎？然後，在相關說明中，您能否談談您的聲明中包含哪些因素，您預計今年將揭開 BiRCh 的神秘面紗，但報告數據取決於花費必要的時間來實現提交級別的品質？有什麼特別的事情可能會延遲讀數嗎？

Yeah. So let me take the second question first. There's nothing that we anticipate would delay. It's just people often say, well, the trial -- if you're going to have the data by the end of the year, can we then expect it on date X? And all we're trying to frame out here is that there'll be the generation of the top-line results. But that process is longer than simply adding the final days.

是的。那我先來回答第二個問題。我們預計不會發生任何延誤。人們經常說，好吧，試驗——如果你要在年底前獲得數據，那麼我們可以在 X 日期期待它嗎？我們在這裡試圖闡明的是，將會產生最重要的結果。但這個過程比簡單地添加最後幾天要長。

It can take a couple of weeks depending on what is going on and what frankly is in the database. But we don't know of anything right now that would suggest that there'd be any kind of delay or impediment to that data being available.

這可能需要幾週的時間，具體取決於發生的情況以及資料庫中的內容。但我們目前還不知道有任何跡象表明這些數據的取得會受到任何延遲或阻礙。

But we just want to caution people that we are saying it will be there by the end of the year. We expect that that will be the case. But depending on how long it takes to sort of clean the database and get it submission ready would dictate when we would ultimately be able to release it.

但我們只是想提醒大家，我們說它將在今年年底前實現。我們預計情況將會如此。但是，清理資料庫和準備提交所需的時間將決定我們最終何時能夠發布它。

I think your other question was why -- what's the confidence in the blended blinded data. I want to be clear, there's not confidence that we see positive outcomes here. We don't -- you can't determine that from blended blinded data. And you always have to be cautious in looking at it.

我認為您的另一個問題是為什麼——混合盲數據的可信度是多少。我想明確指出的是，我們並不確信我們會看到正面的成果。我們不知道——你無法從混合盲數據中確定這一點。而你總是必須小心地觀察它。

What we have seen in the blended blinded data is that the pattern in that blended blinded data would comport with what you would expect to see if the drug were working. That does not indicate that the drug is working. It just means that the profile of patients fits that. So let me give you an example.

我們在混合盲法資料中看到的是，混合盲法資料中的模式與您期望看到的藥物是否有效相符。這並不表示該藥物有效。這僅僅意味著患者的狀況符合這一點。讓我給你舉個例子。

If you're going to see a separation in treatment arms, you would expect to see concentrations of patients having certain response measures. While we can't unblind the data to know who's in which arm, we have seen distinctions between groups of patients which would be consistent with different doses providing different results. And it's occurring at a time in the trial when you would expect that to happen.

如果您要觀察治療組的分離情況，您會看到具有某些反應措施的患者集中。雖然我們無法揭開數據以了解誰在哪一組，但我們已經看到患者組之間存在差異，這與不同劑量提供不同結果的現像一致。而這件事發生在審判過程中，正如你所預料的。

But once again, I want to emphasize not to overinterpret these results. Our confidence in this being effective in CRS without nasal pulps comes from the fact that, really, that condition is almost -- one can think of it like bronchiectasis in the nasal passage. And so it's not dissimilar from bronchiectasis in that regard.

但我再次強調不要過度解讀這些結果。我們相信這種方法對沒有鼻塞的慢性鼻竇炎 (CRS) 有效，因為事實上，這種情況幾乎可以想像成鼻腔支氣管擴張。從這一點來看，它與支氣管擴張並沒有什麼不同。

Now that's a pretty rudimentary biological description. But I think it is appropriate to combine those two pieces of information and at least say we are encouraged that this is directionally going the right way. We'll have to see what the results show. And of course, we all know what the experience can be with clinical trial results. So a word of caution, but I would say we are cautiously optimistic.

這是一個相當基本的生物學描述。但我認為將這兩個訊息結合起來是合適的，至少我們可以說，這在方向上是朝著正確的方向發展的。我們必須看看結果如何。當然，我們都知道臨床試驗結果會帶來什麼樣的體驗。所以需要提醒的是，我們還是謹慎樂觀的。

Very helpful. Thank you.

非常有幫助。謝謝。

Kelly Shi, Jefferies.

Kelly Shi，傑富瑞集團。

Congrats on the progress. For bronchiectasis launch, do you think the eligible patients have exacerbations properly recorded in medical record for all? And any physician feedback on this front? And maybe the strategy implemented in the future help identify all the eligible patients, if not yet. Thanks.

恭喜你取得進展。對於支氣管擴張症的啟動，您是否認為符合條件的患者的病情惡化已正確記錄在所有病歷中？對此有任何醫生的回饋嗎？也許未來實施的策略有助於識別所有符合條件的患者，如果目前還不能的話。謝謝。

Sure. Yeah. I mean, when we size the market at launch at 250,000 roughly, that is consistent with the data cross examinations and correlations that we've done looking at ICD-10 codes, surveying physicians, doing market research. So we feel pretty good about that number as patients that have documented two or more exacerbations within the last 12 months.

當然。是的。我的意思是，當我們在推出時將市場規模定為大約 250,000 時，這與我們查看 ICD-10 代碼、調查醫生、進行市場研究所做的數據交叉檢查和相關性是一致的。因此，作為過去 12 個月內記錄過兩次或兩次以上病情加重的患者，我們對這個數字感到非常滿意。

The unknown is the opportunity that lies beyond that and how proximate it is, how many of those patients that are out there that are perhaps comorbid with COPD or asthma and are tracking exacerbations, but have not yet had the CT scan to determine whether or not there is bronchiectasis present. And that's the gold standard that's needed for those patients.

未知的是，除此之外，還存在著什麼機會，以及這種機會有多近，有多少患者可能同時患有 COPD 或氣喘，並且正在追蹤病情惡化，但尚未進行 CT 掃描以確定是否存在支氣管擴張。這就是這些患者所需要的黃金標準。

So a lot of those patients, I think, are going to get channeled through a CT scan. And I know there are some physicians who are doing that in a very deliberate way because they do believe that there are patients out there.

所以我認為很多患者都會接受 CT 掃描。我知道有些醫生正在非常謹慎地這樣做，因為他們確實相信那裡有病人。

Perhaps a way to ground this for everyone is to return to our WILLOW and ASPEN Phase 2 and 3 study results, where we had between 15% and 20% of patients in those trials that were comorbid with COPD or asthma. And we saw a response from those patients as well.

也許讓每個人都明白這一點的方法是回顧我們的 WILLOW 和 ASPEN 第 2 和第 3 階段研究結果，在這些試驗中，我們有 15% 到 20% 的患者同時患有 COPD 或氣喘。我們也看到了這些患者的反應。

That's what gives us confidence that if we can access that undiagnosed or misdiagnosed patient population, that they'll not only be able to be identified as bronchiectatic but will be responsive to the medication, which is, of course, the goal.

這使我們有信心，如果我們能夠接觸到未確診或誤診的患者群體，他們不僅能夠被確診為支氣管擴張症，而且會對藥物產生反應，這當然是我們的目標。

Thank you.

謝謝。

Graig Suvannavejh, Mizuho.

瑞穗的 Graig Suvannavejh。

Hey, good morning. Thank you for taking my question. I wanted to ask about your interim futility analysis that you're expecting next year in HS. And if you could remind us what the bar for success will be in that interim? And then maybe a follow-up, as you think about next indications for brensocatib, is the view that you will similarly look to do interim futility analyses? Thanks.

嘿，早安。感謝您回答我的問題。我想詢問一下您明年在高中預計進行的中期無效性分析。您能否提醒我們一下，在此期間成功的標準是什麼？然後也許接下來，當您考慮 brensocatib 的下一個適應症時，您是否認為同樣會進行中期無效性分析？謝謝。

Sure. So I think in response to the second question, we don't anticipate taking brenso into any additional indications beyond bronchiectasis, CRS without nasal polyps, and HS. But, Martina, maybe you want to comment on the first question relating to the futility analysis?

當然。因此，我認為在回答第二個問題時，我們預計除了支氣管擴張、無鼻息肉的慢性鼻竇炎和 HS 之外，布倫索不會用於任何其他適應症。但是，瑪蒂娜，也許你想對與無效性分析有關的第一個問題發表評論？

Yeah. So the planning of futility analysis based on the first 100 patients. Just as a reminder, this is an analysis that is -- we're looking for a signal of efficacy, not for a p-value. And that will give us the indication is, are we moving forward? Will we reach a level of efficacy that gives us the confidence that this is a good indication? And -- but you shouldn't be looking for a p-value, but a signal of efficacy.

是的。因此，無效性分析的規劃是基於前 100 名患者。提醒一下，這是一個分析——我們正在尋找功效訊號，而不是 p 值。這將向我們表明，我們是否正在前進？我們能否達到一定的療效水平，讓我們有信心這是一個好的指標？而且——但你不應該尋找 p 值，而應該尋找功效的訊號。

And the way that's going to work is we're going to -- they're going to actually unblind the data to an expert third-party group of physicians who will look at the data in an unblinded fashion to see if there's something going on there.

我們要做的工作是——他們實際上會將數據公開給第三方專家醫生小組，這些醫生將以非盲的方式查看數據，看看是否有問題。

To your earlier question, really the intersection of the two questions, in HS, it's less obvious and there are fewer gold-standard animal models that can inform whether or not any particular medicine is going to be effective. So we've gone into patients in Phase 2. But because of that caution and wanting to make sure we're deploying our capital efficiently, we've done this futility analysis, which won't hit the ultimate p-value.

對於您之前的問題，實際上這兩個問題的交集在 HS 中不太明顯，並且能夠判斷任何特定藥物是否有效的黃金標準動物模型也較少。因此，我們已經進入第二階段的患者治療階段。但出於謹慎，並希望確保我們有效地部署資本，我們進行了無效性分析，這不會達到最終的 p 值。

It's not going -- we're not going to take an alpha hit on this by doing this because we won't see the results. It's only the expert panel, and they're going to essentially give us a thumbs up or down; the trial should continue, or the trial should be stopped. And that's the information we're going to get in the first quarter of next year.

這不會發生——我們不會通過這樣做來對此進行 alpha 打擊，因為我們看不到結果。這只是專家小組，他們基本上會給我們贊成或反對的意見；審判應該繼續，或審判應該停止。這就是我們將在明年第一季獲得的資訊。

While we're not going after other indications with brensocatib, I do want to highlight that we will be entering the clinic next year with our next generation of DPP1 molecules we've been working on since the WILLOW results came out and were so positive. And those will unlock additional indications.

雖然我們不會嘗試使用 brensocatib 來治療其他適應症，但我想強調的是，我們將於明年將下一代 DPP1 分子帶入臨床，自從 WILLOW 結果出來並且非常積極以來，我們一直在研究該分子。這些將會解鎖額外的指示。

We haven't decided what the first one is going to be yet. But we're looking very carefully at things like COPD, like asthma, rheumatoid arthritis, and even IBD. So there's a lot where we can go with this class of molecule. Our confidence will grow with each additional indication that is positive in terms of brenso data.

我們還沒決定第一個是什麼。但我們正在非常仔細地研究慢性阻塞性肺病、氣喘、類風濕性關節炎甚至發炎性腸道疾病等疾病。因此，我們可以利用這類分子做很多事情。隨著布倫索數據中每一個正面的跡像出現，我們的信心就會增強。

So for example, if CRS and HS were to both work, that would be, I think, a stunning revelation from our point of view. And we would really press the pedal down on the next generation of DPP1 for these other indications. Because at that point, we believe we would have validated that we're holding something of a biological skeleton key for neutrophil-mediated diseases.

例如，如果 CRS 和 HS 都能發揮作用，從我們的角度來看，那將是一個驚人的發現。我們將大力開發下一代 DPP1 以用於其他適應症。因為到那時，我們相信我們已經證實我們掌握了中性粒細胞介導疾病的生物學萬能鑰匙。

Will, if I could just quickly follow up, just so on your next-generation DPP1, so what then would be an ideal TPP for your next DPP?

威爾，如果我可以快速跟進一下您的下一代 DPP1，那麼對於您的下一代 DPP 來說，理想的 TPP 是什麼？

Fair enough. We'll have to come up with some new shorthand. I think what we're doing right now -- and this is where our confidence comes in that next generation. With the subsequent indications and really the strength of the brenso results in bronchiectasis, we think there is opportunity for this mechanism to apply in other disease states.

很公平。我們必須想出一些新的速記方法。我認為我們現在所做的事——也是我們對下一代充滿信心的地方。隨著後續適應症的出現以及布倫索在支氣管擴張方面所表現出的強度，我們認為這種機制有機會應用於其他疾病狀態。

And that is not entirely neutrophil-mediated disease speculation. We've done animal models, both with brenso and with the successor molecules. That's why they're basically ready to go into the clinic next year. With that work in hand, we know what each of the different molecules can do in terms of performance in those animal models.

這並不完全是中性粒細胞介導的疾病的推測。我們已經用布倫索和後續分子建立了動物模型。這就是為什麼他們基本上準備在明年進入臨床階段。透過這項工作，我們知道每種不同的分子在這些動物模型中能扮演什麼角色。

And I can tell you that some of those are pretty reliable in terms of their translatability into the clinic. So I think we're excited by the enormous potential that that represents. Because these diseases we're talking about, rheumatoid arthritis, COPD, asthma, IBD, these are very significant indications.

我可以告訴你，其中一些在臨床上的可轉化性是相當可靠的。所以我認為我們對它所代表的巨大潛力感到興奮。因為我們正在談論的這些疾病，類風濕性關節炎、慢性阻塞性肺病、氣喘、發炎性腸道疾病，這些都是非常重要的適應症。

And while they may have a number of other approved or competitive products, we still hold by the standard of first or best-in-class. And so if our drug has a meaningful role to play in those settings, you can expect us to be bringing those subsequent molecules forward.

儘管他們可能有許多其他已獲批准或具有競爭力的產品，但我們仍然堅持一流或最佳的標準。因此，如果我們的藥物在這些環境中發揮重要作用，那麼您可以期待我們將這些後續分子向前推進。

And each -- it's our plan right now that each molecule would have its own dedicated disease it would be targeting, which is somewhat unique and an unintended byproduct of the operation of IRA, where we are constrained down to nine years to get the return on any investment we make on the molecule. As a consequence of that, we actually have to go after the other disease indications using new molecules. And that's why we are where we are.

我們現在的計劃是，每個分子都有其針對的專門疾病，這在某種程度上是獨一無二的，也是 IRA 運作的一個意外副產品，我們被限制在九年內才能獲得對分子的任何投資的回報。因此，我們實際上必須使用新的分子來治療其他疾病。這就是我們目前處境的原因。

Thank you.

謝謝。

Andy Chen, Wolfe Research.

安迪陳，沃爾夫研究公司。

Hey, thank you for taking the question. Another question about CRS without nasal polyps. Our understanding here is that it's both driven by eosinophils and neutrophils.

嘿，謝謝你回答這個問題。另一個問題是關於沒有鼻息肉的慢性鼻竇炎 (CRS)。我們的理解是，它是由嗜酸性粒細胞和中性粒細胞共同驅動的。

Just wondering, in your understanding of the disease, is it heterogeneous on a population level as in that there are separate endotypes of different patients driven differently by different cells? Or is it on an individual patient level as in each patient is heterogeneous and has contribution from both sides? Thank you.

只是想知道，根據您對這種疾病的理解，它在人群層面上是否具有異質性，即不同患者有不同的內型，由不同的細胞驅動？還是在個別患者層面，因為每個患者都是異質的並且有來自雙方的貢獻？謝謝。

It's really interesting. We saw in our ASPEN data that there was not much of a distinction at -- looking at eosinophil levels up to -- I think it was 750. And we had originally stratified the study to accommodate for the potential differential performance in the very phenotypes you're describing or endotypes you're describing, where it's a mix of eosinophil- and neutrophil-driven disease.

這真的很有趣。我們在 ASPEN 數據中看到，嗜酸性粒細胞水平最高時沒有太大區別——我認為是 750。我們最初對研究進行了分層，以適應您所描述的表型或內型中的潛在差異表現，其中混合了嗜酸性粒細胞和中性粒細胞驅動的疾病。

That is quite, we felt, a regulatory discovery. And it means that we don't have to worry as much about that, at least up to that threshold of eosinophil counts. And those mixed-profile patients, we expect to be responsive because they were in the ASPEN study.

我們認為，這確實是一個監管上的發現。這意味著我們不必太擔心，至少在嗜酸性粒細胞計數的閾值以下。我們預期那些混合型患者會有反應，因為他們參與了 ASPEN 研究。

As we look forward, that also does open the door to thinking about CRS with nasal polyps, which may be more eosinophil-driven but where we may also be able to have a beneficial effect. So that's something we're reflecting. I don't know, Martina, if you want to add anything to that.

展望未來，這也確實為思考伴隨鼻息肉的慢性鼻竇炎打開了大門，這種疾病可能更多地由嗜酸性粒細胞驅動，但我們也可能產生有益的影響。這就是我們正在反思的事情。我不知道，瑪蒂娜，你是否想補充一些內容。

Yeah. Maybe just with regards to the endotypes, you're right; similar like what you've seen now in bronchiectasis, endotypes are more defined of what is the biologic driver behind it. So is it neutrophils? Is it eosinophils?

是的。也許僅就內型而言，您是對的；類似於您現在在支氣管擴張中看到的，內型更明確地說明了其背後的生物學驅動因素。那麼它是中性粒細胞嗎？是嗜酸性粒細胞嗎？

And we don't only look at the two big groups. There are subgroup, and neutrophils play a role in all of the endotypes. There are -- there is one endotype that is really more driven or largely driven that's eosinophilic. But the largest proportion of patients in CRS is driven by a mixed endotype or strongly neutrophil-driven endotype.

我們不僅僅關注這兩大群體。有亞群，中性粒細胞在所有內型中都發揮作用。有一種內型實際上更具驅動力或主要受嗜酸性粒細胞驅動。但 CRS 患者中絕大多數是由混合內型或強中性白血球驅動的內型所致。

Thank you.

謝謝。

Vamil Divan, Guggenheim Partners.

瓦米爾·迪萬，古根漢合夥人。

Hi, this is Daniel, on for Vamil. Thanks for taking our question. Just another one on the already diagnosed bronchiectasis population. So yeah, you described this as being around 500,000 patients, half of which have had two-plus exacerbations in the last year.

大家好，我是丹尼爾，代表 Vamil。感謝您回答我們的問題。這只是已確診的支氣管擴張症族群中的另一個病例。是的，您描述的是大約有 50 萬名患者，其中一半在去年病情加重了兩次以上。

So can you maybe discuss if there's any variability between doctors and patients on what they define exactly as an exacerbation in their real-world practice? I guess, kind of getting to the idea that once the drug is available, is it possible that the number of exacerbations that are being identified potentially goes up? Or maybe they're being under-represented right now there's no drug available for this indication? Thank you.

那麼，您能否討論一下，在現實實踐中，醫生和患者對於病情加重的具體定義是否存在差異？我想，一旦這種藥物上市，是否有可能發現病情加重的次數增加？或者他們目前代表性不足，沒有藥物可以治療這種症狀？謝謝。

Yeah. So I think, look, whenever you're talking about a new treatment for a disease that has nothing to treat it, there is a whole cascade of a greater awareness that kicks off. And that almost always results in more patients being identified, more of the symptoms that help identify those patients being tracked and being looked for.

是的。所以我認為，每當你談論一種針對一種尚無治療方法的疾病的新療法時，就會引發一系列更深刻的認識。這幾乎總是會導致更多的病人被識別，更多有助於識別病人的症狀被追蹤和尋找。

You're just raising the index of suspicion among physicians and patients. And that's really the key objective of any disease state awareness campaign, is to ask the question, what is causing the symptoms that I have? That's also a question that gets engaged with a lot of extra energy now in a world where our drug is approved as we expect next week.

你只是增加了醫生和病人的懷疑程度。這確實是任何疾病狀態意識運動的關鍵目標，即提出這樣的問題：是什麼導致了我出現的症狀？在我們的藥物預計下週獲得批准的情況下，這個問題現在也引起了廣泛的關注。

That opens the door to an answer to the question of what to do if you have it. Whereas right now, a physician who determines that this patient has exacerbations as a byproduct of bronchiectasis, there's nothing they have to offer them other than some basic airway clearance.

這為我們解答「如果感染了這種病毒該怎麼辦」這個問題打開了大門。而現在，醫生確定該患者的病情惡化是支氣管擴張的副作用，除了一些基本的呼吸道清理之外，他們沒有什麼可以提供的。

So I think this is a dynamic that we're very interested to see how it will play out. Because we are aware of that other significant bolus of patients behind the ones we've identified today, that could be eligible for treatment.

所以我認為這是一個動態，我們非常感興趣看看它將如何發揮作用。因為我們知道，除了今天確定的患者之外，還有大量患者可能有資格接受治療。

And I think the ability for physicians and patients to recognize those exacerbations and document them lays the groundwork for them becoming -- patients who would be potentially appropriate and, therefore, potentially benefit from the medicine if it's approved, as we expect, next week.

我認為，醫生和患者能夠識別這些病情惡化並記錄下來，為他們成為可能適合的患者奠定了基礎，因此，如果該藥物如我們預期的那樣在下週獲得批准，他們就有可能從中受益。

I couldn't be more excited about the possibility to make a dent in this disease space. It's important to remember that this disease has been around since the early 19th century when it was first identified. And it has yet to have anything approved to treat it. So I can't overstate, I think, how significant the arrival of this medicine will be if and when it's approved.

我對能夠在這一疾病領域取得進展的可能性感到無比興奮。重要的是要記住，這種疾病自 19 世紀初首次被發現以來就已經存在。目前還沒有任何藥物核准用於治療此病。因此，我認為，如果這種藥物獲得批准，它的到來將具有多麼重要的意義。

Jennifer Kim, Cantor Fitzgerald.

珍妮佛金 (Jennifer Kim)，費茲傑羅領唱。

Thank you for taking my questions, and congrats on the progress. Maybe to touch on market access again, I know you said that a simple attestation seems reasonable in terms of upfront ease of access. I wanted to ask about the reauthorization process and how those conversations have been going? Are there any expectations in terms of requirements on that end?

感謝您回答我的問題，並祝賀您的進展。也許再次談到市場准入，我知道您說過，從前期的准入便利性來看，簡單的證明似乎是合理的。我想詢問重新授權流程以及這些對話的進展？這方面有什麼要求嗎？

Yeah. So our strategy here, as the first-ever approved medicine in disease, we absolutely do not need to contract if we don't want to in terms of how we're approaching the market access world. We're choosing to do so because our objective with that modest give, if you will, upfront, to create that frictionless launch and reauthorization process.

是的。因此，我們的策略是，作為首個獲得批准的疾病治療藥物，如果我們不想在市場准入方面簽訂合同，我們絕對不需要簽訂合約。我們選擇這樣做是因為我們的目標是透過預先提供適度的幫助來創建無摩擦的啟動和重新授權流程。

And reauthorization is absolutely a contemplated part of our discussion and negotiation with the market access world. As Roger said, we've observed that these discussions have been going very well. I think it's fair to say that everybody recognizes the need for a medicine.

重新授權絕對是我們與市場准入領域討論和談判中考慮的一部分。正如羅傑所說，我們觀察到這些討論進展非常順利。我認為可以公平地說，每個人都認識到藥物的必要性。

This medicine's safety and efficacy profile is particularly compelling. So it is not a contentious interaction when we talk about how do we facilitate appropriate patients to get on the drug, how do we ensure that they can remain on the drug and receive benefit. And I think we're in extremely good state as it relates to that.

這種藥物的安全性和有效性尤其引人注目。因此，當我們談論如何幫助合適的患者服用藥物，如何確保他們能夠繼續服用藥物並獲得益處時，這並不是一個有爭議的互動。我認為就此而言，我們的狀態非常好。

And that's helpful. If I could ask one more. Just a question on launch analogs and the dynamics over the next couple of quarters. How should we think about, I guess, the launch in the fourth quarter with out-of-pocket max for Medicare patients? And then how that then, I guess, proceeds into 2026 once it resets?

這很有幫助。如果我可以再問一個。這只是關於發布類似物和未來幾季的動態的一個問題。我想，我們應該如何看待第四季推出的針對醫療保險病患的最高自付費用政策？那麼，我猜，一旦重置，它將如何持續到 2026 年？

Yeah. That's a new feature, obviously. I'll ask Roger to address that.

是的。顯然，這是一個新功能。我會請羅傑來解決這個問題。

Yeah. So I think that as you think about the smoothing and you think about the Medicare over -- where you can spread out the payments over the full months, I think in the fourth quarter, we probably come in where we're actually in a pretty advantaged position where most patients have probably worked through their copay burden for the full year.

是的。因此，我認為，當您考慮平滑度並考慮醫療保險時 - 您可以將付款分攤到整個月份，我認為在第四季度，我們可能會處於非常有利的位置，大多數患者可能已經解決了全年的共同支付負擔。

We'll see as we go into 2026 and the first quarter. That's a reset that's always historically been a challenge. I'm hopeful that as this will be the second year that this is implemented, that perhaps it's a more smooth process this year, as patients and payers and so forth and pharmacies get used to that.

我們將在 2026 年第一季看到結果。從歷史上看，這是一個一直充滿挑戰的重置。我希望，由於這是實施該政策的第二年，隨著患者、付款人等以及藥房逐漸習慣這一點，今年的進程可能會更加順利。

But we'll see. So -- and we stand ready to support as we can our patients in any kind of out-of-pocket burden that we can address directly.

但我們會看到。因此，我們隨時準備為我們的患者提供力所能及的支持，幫助他們解決任何我們可以直接解決的自付費用負擔。

Thank you.

謝謝。

Leonid Timashev, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Leonid Timashev。

Hey, thanks for taking my question. I wanted to ask on the launch or maybe more specifically, how you're thinking about what the shape might be of a launch in Europe, and your commitment to Europe and ex-US geographies given both the MFN dynamics. And just if there's any differences in how physicians are thinking about their level of excitement for the drug in Europe versus the US as well? Thanks.

嘿，謝謝你回答我的問題。我想問一下關於發布的問題，或者更具體地說，您如何考慮在歐洲推出該產品的形式，以及考慮到最惠國待遇的動態，您對歐洲和美國以外地區的承諾。那麼歐洲和美國的醫生對於這種藥物的興奮程度是否有差異呢？謝謝。

So I would say that the enthusiasm is sort of universal or uniform. Most of the congresses that we go to are international in their scope and engagement.

所以我想說這種熱情是普遍的或統一的。我們參加的大多數會議在範圍和參與度上都是國際性的。

And as a consequence, we have relationships by virtue of ARIKAYCE's approval in the US, Europe, and Japan, with all of those physicians. And so we've had the benefit of their perspective as we've traveled this journey in the development of a bronchiectasis medicine.

因此，憑藉 ARIKAYCE 在美國、歐洲和日本的批准，我們與所有這些醫生建立了關係。因此，我們在開發支氣管擴張藥物的過程中受益於他們的觀點。

And I would say it's equal there as it is here. And so that creates a hopeful opportunity. I think that's echoed by the fact that the regulatory interactions to date in Europe, the UK, have been extremely positive as they have been with the US. And that sets us on a trajectory where we'll be able to launch in Europe and then Japan next year.

我想說那裡的情況和這裡的情況是一樣的。這創造了一個充滿希望的機會。我認為，迄今為止，歐洲、英國與美國的監管互動一直非常積極，這與此相呼應。這為我們奠定了基礎，我們將能夠在明年在歐洲和日本推出產品。

On the discussion of the issue of how we're going to approach those territories, we have that infrastructure. We've been very successful with ARIKAYCE in those regions as is so clearly demonstrated this quarter, were both outperformed. And I think that's extremely encouraging because that experience in that dynamic, that's positive with those physicians in the ARIKAYCE setting, we believe, will translate over into bronchiectasis.

在討論我們將如何處理這些領土的問題時，我們已經擁有了相應的基礎設施。正如本季所清楚表明的那樣，我們在這些地區的 ARIKAYCE 取得了巨大成功，均表現出色。我認為這非常令人鼓舞，因為我們相信，在這種動態中的經驗，對於 ARIKAYCE 環境中的那些醫生來說是積極的經驗，將轉化為支氣管擴張。

So I think it's a very positive picture. We'll see. The launches will be next year. I'll remind everybody that when we priced ARIKAYCE, we set the list price at the same level in the US, Europe, and Japan. We thought that was the right thing to do.

所以我認為這是一幅非常正面的畫面。我們拭目以待。發射將於明年進行。我要提醒大家的是，當我們為ARIKAYCE定價時，我們將標價設定在美國、歐洲和日本的同一水平。我們認為這是正確的做法。

That's our best effort to make sure that everybody is investing in the innovation that we're bringing after all these years of development. And so we'll see how this all plays out as we move forward. Hopefully, that addresses your question.

這是我們最大的努力，以確保每個人都投資於我們經過多年發展所帶來的創新。因此，我們將拭​​目以待，看看這一切在未來會如何發展。希望這能解答您的問題。

Trung Huynh, UBS.

Trung Huynh，瑞銀。

Hi, guys, This is [Noah], on for Trung. Thanks for taking our question. Just -- for us, we're wondering, is there any potential read-through from the BiRCh trial to CEDAR if BiRCh reads out positive?

大家好，我是 [Noah]，代表 Trung 發言。感謝您回答我們的問題。只是——我們想知道，如果 BiRCh 的讀數呈陽性，BiRCh 試驗是否有可能對 CEDAR 產生影響？

And then also just looking for a clarification on the futility analysis in CEDAR. We're just wondering, is that focused primarily on the primary endpoint of change in abscesses and nodules? Or do clinical response also play a role in the futility analysis?

然後也只是想尋求對 CEDAR 中的無效性分析的澄清。我們只是想知道，這是否主要關注膿瘍和結節變化的主要終點？或者臨床反應在無效性分析中也發揮了作用？

I think as you go from BiRCh to CEDAR, I'm just going to say -- I've said this publicly many times. I'm excited by the possibility of BiRCh because CRS without nasal polyps, again, as I said, rudimentally -- in a rudimentary sense is kind of bronchiectasis in the nasal passage. So I'm hopeful that we'll see some positive results or trends in that study that would encourage us to go into Phase 3.

我認為，當你從 BiRCh 轉到 CEDAR 時，我只想說——我已經公開說過很多次了。我對 BiRCh 的可能性感到興奮，因為沒有鼻息肉的 CRS，正如我所說，從根本上講 - 從根本上講是一種鼻腔支氣管擴張。因此，我希望我們能夠在該研究中看到一些積極的結果或趨勢，從而鼓勵我們進入第三階段。

HS is a much trickier disease. And I think there are a number of variables that surround that, which include the patient profile that you're targeting. So we've gone from moderate to severe patients. We could have targeted mild to moderate. There's -- in that patient selection process, you introduce some uncertainties about the ability of your drug to have an impact. There aren't great animal models.

HS 是一種更為棘手的疾病。我認為這其中涉及許多變量，包括您所針對的患者概況。因此，我們的患者已從中度轉為重度。我們本可以將目標鎖定在輕度至中度。在患者選擇過程中，您會對藥物產生影響的能力產生一些不確定性。沒有很好的動物模型。

So I would put the uncertainty around CEDAR much, much higher than I would have been around CRS at least as far as the logic goes. And that's why we built the futility analysis. So they could go in and look at all the data and make their conclusion about whether this study should proceed. Because we certainly don't want patients experimenting with the medicine if it's not going to be a benefit.

因此，至少從邏輯上講，我認為 CEDAR 的不確定性比 CRS 的不確定性要高得多。這就是我們建立無用性分析的原因。因此他們可以查看所有數據並得出是否應該繼續進行這項研究的結論。因為如果藥物沒有益處，我們當然不希望病人嘗試這種藥物。

I don't know, Martina, if you had anything you want to add about that.

我不知道，瑪蒂娜，您是否還有什麼要補充的。

Yeah. And the futility analysis will be focusing on the primary endpoint. So it will be the percentage change of a nodule count to week 16. And the reason that is the focus because this is where you see the immediate change as secondary endpoints. And by the end of week 52, that we will also look, of course, at high scores 50 or high score 75. So -- but the interim will focus on the primary endpoint.

是的。無效性分析將集中於主要終點。因此這將是第 16 週結節計數的百分比變化。之所以將其作為焦點，是因為您可以在這裡看到作為次要終點的直接變化。到第 52 週結束時，我們當然也會關注高分 50 或高分 75。所以——但中期將重點放在主要終點。

Stephen Willey, Stifel.

史蒂芬威利（Stephen Willey），Stifel。

Yeah, good morning. Thanks for taking the question. Should we expect registration of TPIP development in PAH to be limited to a single Phase 3 trial? Or do you think a broader sotatercept-like development program may be in different functional class, and risk subgroups make more sense here just given the strength of the Phase 2 data?

是的，早安。感謝您回答這個問題。我們是否應該預期 PAH 中 TPIP 開發的註冊僅限於單一的 3 期試驗？或者您認為更廣泛的類似 Sotatercept 的開發計劃可能屬於不同的功能類別，並且僅考慮到第 2 階段資料的強度，風險亞組在這裡更有意義？

Yeah. I think we'll know more once we've had the October meeting with FDA, to be candid. And I think our enthusiasm for this program as we have dug into the data and the aftermath of the top-line results, I would say, has grown and accelerated to the point where -- as Martina mentioned a moment ago, the result of the TETON study are going to be something we watch very carefully.

是的。坦白說，我認為一旦我們十月與 FDA 舉行會議，我們就會知道更多。我認為，隨著我們深入研究數據和頂線結果，我們對這個項目的熱情已經增長並加速到一定程度——正如 Martina 剛才提到的，我們將非常密切地關注 TETON 研究的結果。

We know how sotatercept is perceived and what a positive contribution that is to the disease state. Remind you that that can only be operative in PAH. So it doesn't have a role to play in PH-ILD. We're sitting with what we believe to be the best clinical profile based on the Phase 2 data for PAH, for PH-ILD, and now possibly for IPF, depending on how the TETON study reads out.

我們知道索他西普是如何被感知的，以及它對疾病狀態有何正面貢獻。提醒您，這只能在 PAH 中起作用。因此它在 PH-ILD 中不起作用。根據 TETON 研究的結果，我們認為根據 PAH、PH-ILD 和現在可能 IPF 的第 2 階段數據，我們得出了最佳的臨床概況。

With that set of opportunities, we would then obviously pursue our own data in IPF. But that's a really significant profile to be in possession of. And so I think we're going to move aggressively after every opportunity. I don't know, Martina, do you want to comment on any of the sub approaches that sotatercept has taken in our approach to that?

有了這些機會，我們顯然會在 IPF 中尋找我們自己的數據。但擁有這樣的個人資料確實非常重要。因此我認為我們會抓住每一個機會積極行動。我不知道，瑪蒂娜，您是否想評論 Sotatercept 在我們的方法中採取的任何子方法？

Yeah. So I think we have to have the discussions with the agency on the number of trials or also how trial designs will look like. We will, of course, take into account that sotatercept is on the market and how we will design the trial, reflecting sotatercept.

是的。因此我認為我們必須與該機構討論試驗的次數或試驗設計。當然，我們會考慮到 Sotatercept 是否已上市，以及我們將如何設計試驗以反映 Sotatercept。

At this point, we can't speculate of what will be the effect size on top of it. But we know that with the Phase 2 data, the profile, both on the efficacy and on the safety, is the strongest one that we think in the prostanoid group. So we have very strong confidence level on TPIP. And then we'll see what, on top of it, sotatercept, how that would look like.

目前，我們無法推測其影響大小。但我們知道，根據第 2 階段的數據，我們認為前列腺素類藥物的療效和安全性都是最強的。因此，我們對TPIP抱持非常強烈的信心。然後，我們將看看索他西普 (sotatercept) 會是什麼樣子。

We are also able -- and you've seen this in the Phase 2 study -- to reach higher doses and therefore, have the opportunity to deliver significant efficacy impact that may sometimes be an opportunity to also go to lower doses on sotatercept, which is a very good drug. But you always look at it in context of what is your overall benefit risk, what is your safety profile. So I think that remains to be seen, but we will design the trial to make sure we can answer these questions.

我們也能夠——正如您在第二階段研究中看到的——達到更高的劑量，因此有機會產生顯著的療效影響，有時這也可能是一個機會，讓我們可以降低索他西普的劑量，這是一種非常好的藥物。但您總是會從您的整體利益風險、您的安全狀況的角度來看待它。所以我認為這還有待觀察，但我們將設計試驗以確保我們能夠回答這些問題。

All right. Thanks.

好的。謝謝。

Maxwell Skor, Morgan Stanley.

摩根士丹利的馬克斯韋爾·斯科爾。

Great. Thank you for squeezing me in, and congrats on dosing the first DMD patient in the ASCEND trial. I was just hoping you could share any early operational and clinical insights into that experience. And how does your intrathecal delivery differentiate 1201 from other gene therapy approaches in DMD? Thank you.

偉大的。感謝您抽出時間讓我加入，並祝賀您在 ASCEND 試驗中為第一位 DMD 患者進行給藥。我只是希望您能分享有關該經驗的任何早期操作和臨床見解。鞘內給藥如何將 1201 與 DMD 中的其他基因治療方法區分開來？謝謝。

So I will just say so far, so good. Caution is the watchword around anything to do with gene therapy these days. And we have, I would say, a belt-and-suspenders approach to each and every patient that we are bringing into this. It must be enormously unsettling for parents with kids who suffer from this disease to have experienced what is going on recently in this space.

所以我只想說，到目前為止一切都很好。如今，謹慎是有關基因治療的一切的口號。我想說的是，我們對每一位接受治療的患者都採取了雙重保險的治療方法。對於孩子患有這種疾病的父母來說，經歷最近這種疾病的發生一定讓他們非常不安。

We set out four years ago when we bought Motus to give support to Bryan's vision that an intrathecal delivery route would improve safety and efficacy. And the early animal data work that was conducted validated those ideas.

四年前，我們收購了 Motus，以支持 Bryan 的願景，即鞘內給藥途徑可以提高安全性和有效性。早期進行的動物數據研究證實了這些想法。

I think we're anxious to see what the human data, obviously, will show. But we're going to be going very cautiously and slowly given the experience. Recall that part of the reason for intrathecal delivery as an exciting innovation is you don't have that first-pass liver effect.

我認為我們急切地想看看人類數據顯然會顯示什麼。但鑑於以往的經驗，我們將非常謹慎和緩慢地前進。回想一下，鞘內給藥作為一項令人興奮的創新的部分原因是您沒有首過肝臟效應。

And the consequence of that is you can dose less virus to the patient. And notwithstanding all of that, the transduction efficiency that we saw in muscle and even cardiac tissue was remarkable. And so it is for those reasons that we think a lower dose, greater efficacy, potentially greater safety may be the profile of this treatment when it's -- when all is said and done.

這樣做的結果是，你可以減少患者所感染的病毒數量。儘管如此，我們在肌肉甚至心臟組織中看到的傳導效率還是非常驚人的。因此，基於這些原因，我們認為，當一切都塵埃落定時，較低的劑量、更高的療效、潛在的更高的安全性可能是這種治療方法的特徵。

Great. Thank you.

偉大的。謝謝。

I want to make one other comment. Actually, Martina, do you want to address that one other issue that we want to make sure people are aware of, that is distinct and important for us versus others in the gene therapy space in DMD?

我想再說一點。實際上，Martina，您是否想談談我們希望人們意識到的另一個問題，這個問題對於我們與 DMD 基因治療領域的其他機構相比具有獨特性和重要性？

Yeah. One of the advantages right now on the IT delivery that we can -- that we have is we do not have weight-based dosing in our study. And I think that is a different approach also.

是的。目前我們在 IT 交付方面的優勢之一是，我們的研究中沒有基於體重的劑量。我認為這也是一種不同的方法。

We have now reached the end of our question-and-answer session. Ladies and gentlemen, this concludes today's call. Thank you, all, for joining. You may now disconnect.

我們的問答環節現已結束。女士們、先生們，今天的電話會議到此結束。謝謝大家的參與。您現在可以斷開連線。