Insmed Inc (INSM) 2024 Q3 法說會逐字稿

Thank you for standing by. My name is [Jeannie] and I will be your conference operator today. At this time I would like to welcome everyone to the Insmed third quarter, 2024 financial results conference call.

感謝您的支持。我的名字是 [Jeannie]，今天我將擔任您的會議主持人。現在，我歡迎大家參加 Insmed 2024 年第三季財務業績電話會議。

(Operator Instructions)

（操作員指令）

Thank you. I would now like to turn the conference over to Brian Dunn, Head of Investor Relations. You may begin.

謝謝。現在，我想將會議交給投資者關係主管 Brian Dunn。你可以開始了。

Thank you, Jeannie. Good day, everyone and welcome to today's conference call to discuss Insmed's third quarter, 2024 financial results and provide a business update. I am joined today by Will Lewis Chair and Chief Executive Officer; and Sarah Bonstein, Chief Financial Officer, who will each provide prepared remarks after which they will be joined by Martina Flammer, Chief Medical Officer, for the Q&A session.

謝謝你，珍妮。大家好，歡迎參加今天的電話會議，討論 Insmed 2024 年第三季的財務業績並提供業務更新。今天與我一起出席的還有董事長兼執行長威爾劉易斯 (Will Lewis)；以及財務長 Sarah Bonstein 將會發表準備好的講話，之後首席醫療官 Martina Flammer 將會加入她們的問答環節。

Before we start, please note that today's call will include forward-looking statements based on our current expectations. These statements represent our judgment as of today and inherently involve risks and uncertainties that may cause actual results to differ materially from the results discussed. Please refer to our filings with the securities and exchange commission for more information concerning the risk factors that could affect the company.

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。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結果有重大差異。有關可能影響公司的風險因素的更多信息，請參閱我們向美國證券交易委員會提交的文件。

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. I will now turn the call over to Will for prepared remarks.

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。它並非用於促銷目的，也不足以用於規定決策。現在我將把電話轉給威爾，請他發表準備好的發言。

Thank you, Brian and welcome everyone. The announcement of the positive ASPEN data earlier this year marked the start of a new era for Insmed one that will be defined by our ability to execute on the many opportunities we have in front of us. Our performance, this quarter demonstrated the level of execution, that level of execution sets us up for this exciting new chapter of Insmed's story.

謝謝你，Brian，歡迎大家。今年稍早發布的 ASPEN 積極數據標誌著 Insmed 新時代的開始，這個新時代的開始將取決於我們抓住眼前眾多機會的能力。本季的表現展示了我們的執行水平，這種執行水平為 Insmed 故事激動人心的新篇章奠定了基礎。

The opportunities before us are significant, not only in terms of their potential impact on patients and our company, but also in terms of their sheer quantity. I'm proud to say that, our team across the organization have continued to show a remarkable ability to deliver simultaneously on all of them.

我們面前的機會是巨大的，不僅就其對患者和我們公司的潛在影響而言，而且就其數量而言。我很自豪地說，我們整個組織的團隊繼續展現出同時完成所有任務的卓越能力。

For example, in the third quarter, our commercial team once again, delivered double digit year over year sales growth for ARIKAYCE across all of our regions. At the same time, the US team was also working to build out its infrastructure by nearly tripling its sales force in preparation for the expected launch of brensocatib in the middle of 2025.

例如，在第三季度，我們的商業團隊再次為 ARIKAYCE 在所有地區實現了兩位數的年銷售額成長。同時，美國團隊也在努力建立基礎設施，將銷售團隊擴大近三倍，為預計 2025 年中期推出的 brensocatib 做準備。

Similarly, our clinical development team remains on track to file the NDA for brensocatib in the US this quarter, while at the same time, they have been driving increased enrollment rates across our ongoing clinical trials and working to present and publish data from the ASPEN trial.

同樣，我們的臨床開發團隊仍按計劃於本季在美國提交 brensocatib 的 NDA，同時，他們一直在推動我們正在進行的臨床試驗的入組率提高，並致力於展示和發布 ASPEN 試驗的數據。

Today, I intend to highlight the progress we have made across multiple ongoing initiatives at Insmed and why this progress should add to confidence in our ability to execute on the tremendous opportunities ahead.

今天，我打算強調我們在 Insmed 正在進行的多個計劃中所取得的進展，以及為什麼這些進展應該增強我們抓住未來巨大機會的能力的信心。

Let's begin with brensocatib, earlier this month at the American College of Chest Physicians Annual Meeting in Boston, we presented subpopulation data from 19 prespecified categories from the ASPEN trial based on baseline patient demographics, comorbidities and disease severity measures. Within those 19 categories existed dozens of subgroups, which emphasizes how robust and comprehensive this data presentation was in a population that is known to be very heterogeneous.

讓我們從 brensocatib 開始吧，本月早些時候在波士頓舉行的美國胸腔科醫師學會年會上，我們根據患者基線人口統計、合併症和疾病嚴重程度指標，展示了 ASPEN 試驗中 19 個預先指定類別的亞群數據。在這 19 個類別中存在著數十個子群，這強調了在已知非常異質的群體中資料呈現的穩健性和全面性。

It was remarkable how broadly beneficial treatment was with brensocatib was observed to be across these various subgroupings, which is similar to what we had observed in the Phase 2 WILLOW trial. We continue to expect to file the NDA for brensocatib in the fourth quarter of this year, presuming that filing is accepted, we would expect to announce the acceptance along with the expected timelines for a decision by the FDA in the first quarter of 2025.

值得注意的是，在這些不同的亞群中，brensocatib 的治療具有廣泛的有益性，這與我們在第 2 階段 WILLOW 試驗中觀察到的情況相似。我們繼續預計將在今年第四季度提交 brensocatib 的 NDA，假設申請被接受，我們預計將在 2025 年第一季宣布接受該申請以及 FDA 做出決定的預計時間表。

Moving to our US commercial launch preparations, I'm pleased to report that all 120 new US based sales reps have been trained and are currently deployed in the field, bringing our total sales reps to 184. These additional sales territories have been constructed based on claims data showing us where the diagnosed patients are being treated.

談到我們在美國商業發布的準備工作，我很高興地報告，所有 120 名新的美國銷售代表都已接受培訓並已部署到現場，使我們的銷售代表總數達到 184 名。這些額外的銷售區域是根據索賠數據建立的，這些數據向我們展示了確診患者接受治療的地點。

Our intention is to have broad sales representation from day one, not just in the academic centers and centers of excellence, but also in the community pulmonologists offices where many of these patients receive care. In fact, the US sales force is intentionally sized to enable Insmed to call on every pulmonologist in the United States. We believe that these early investments will position brensocatib for a strong successful launch in bronchiectasis pending FDA approval.

我們的目的是從第一天起就擁有廣泛的銷售代表，不僅在學術中心和卓越中心，而且還在許多患者接受護理的社區肺病專家辦公室。事實上，美國銷售團隊的規模是經過精心設計的，以便 Insmed 能夠聯繫到美國的每位肺病專家。我們相信，這些早期投資將為 brensocatib 在獲得 FDA 批准後在支氣管擴張治療領域取得巨大成功奠定基礎。

Let me also provide an update on the two additional indications we are currently pursuing with brensocatib chronic rhinosinusitis, without nasal polyps and hidradenitis suppurativa. The Phase 2 BiRCH study in CRS without nasal polyps has been rapidly bringing new sites online in Europe and in the US and is now more than 40% enrolled with many more patients currently in screening. We continue to anticipate top line results by the end of 2025. Our Phase 2 HS study is also steadily progressing on schedule towards its first site being opened before the end of this year. The study which will be called CEDAR is expected to enroll approximately 204 subjects randomized 1 to 1 to 1 to receive brensocatib10 miligrams, brensocatib 40 miligrams for matching placebo once per day.

我還要提供我們目前正在研究的 brensocatib 另外兩種適應症的最新情況：不伴隨鼻息肉的慢性鼻竇炎和化膿性汗腺炎。針對不伴隨鼻息肉的慢性鼻竇炎 (CRS) 的 BiRCH 第 2 階段研究已在歐洲和美國迅速建立新的研究點，目前研究入組率已超過 40%，並且正在接受篩檢的患者數量還有更多。我們繼續預計 2025 年底的營收業績。我們第二階段的 HS 研究也正在按計劃穩步推進，預計今年年底前開放第一個站點。這項名為 CEDAR 的研究預計將招募約 204 名受試者，以 1 比 1 的比例隨機分配每天一次接受 brensocatib10 毫克、brensocatib 40 毫克以及匹配安慰劑。

The primary endpoint in the study will be percent change from baseline in total abscess and inflammatory nodule counts measured at week 16. The study is then expected to continue until week 52, with those randomized to the brensocatib arms continuing to receive that same dose. Those who are randomized to the placebo arm would join one of the brensocatib arms at week 16 based on randomization which would also have occurred at baseline on a blinded basis.

研究的主要終點是第 16 週測量的總膿瘍和發炎結節計數相對於基線的百分比變化。預計研究將持續到第 52 週，隨機分配到 brensocatib 組的患者將繼續接受相同劑量。那些被隨機分配到安慰劑組的患者將在第 16 週根據隨機化原則加入其中一個 brensocatib 組，這也將在基線時以盲法方式進行。

As we have signaled in the past, the study will include an interim futility analysis conducted by an independent data monitoring board which will examine data from approximately half of the patient population once they reach week 16. This will allow us to stop the study early if the data does not look promising.

正如我們過去所暗示的那樣，這項研究將包括一項由獨立數據監測委員會進行的中期無效性分析，該委員會將在患者到達第 16 週後檢查大約一半患者群體的數據。如果數據看起來不太樂觀，這將使我們能夠提前停止研究。

If the recommendation from that interim analysis is to continue the study, we will remain blinded to the data that is reviewed by the monitoring board. There is no interim efficacy analysis built into the trial design, so there is no potential for early stoppage due to overwhelming efficacy.

如果中期分析的建議是繼續研究，我們將繼續對監測委員會審查的數據視而不見。試驗設計中沒有包含中期療效分析，因此不存在因療效太過明顯而提前停止的可能性。

If the study continues to completion, we would read out the top line results after all patients reach week 16. We expect more details for this trial to become available on clinicaltrials.gov before the end of this year, and we look forward to providing updates as the trial progresses.

如果研究繼續完成，我們將在所有患者達到第 16 週後讀出最重要的結果。我們預計今年年底前將在 clinicaltrials.gov 上公佈有關該試驗的更多詳細信息，並且我們期待在試驗進展過程中提供最新消息。

Now turning to ARIKAYCE, which posted its seventh consecutive quarter of double digit year over year revenue growth in the third quarter of 2024. We have become accustomed to seeing this level of growth from ARIKAYCE, but when you remember that ARIKAYCE is now in its seventh year post launch, it makes the achievement all the more unique and impressive.

現在來看看 ARIKAYCE，該公司在 2024 年第三季連續第七個季度實現兩位數的年收入成長。我們已經習慣了看到 ARIKAYCE 取得這種程度的增長，但是當你記得 ARIKAYCE 成立至今已有七年時，這一成就就顯得更加獨特和令人印象深刻。

In addition to strong commercial execution, we are also making great strides clinically. Last quarter, we stated our intention to stop screening new patients for the Phase 3 encore study by the end of the third quarter. Thanks to very strong recruitment. We were able to close the screening of new patients a little ahead of that schedule, while we won't know the exact enrollment number until all patients have finished the six to eight week screening process, I'm pleased to report that we have already randomized more patients than the trial's target enrollment of 400 participants.

除了強大的商業執行力，我們在臨床上也取得了長足的進步。上個季度，我們表示打算在第三季末停止對第三階段再研究的新患者進行篩檢。感謝非常強大的招募。我們能夠比計劃提前一點完成新患者的篩選，儘管我們直到所有患者完成六到八週的篩選過程後才會知道確切的入組人數，但我很高興地報告，我們已經隨機分組的患者人數超過了該試驗的目標入組人數 400 名參與者。

Importantly, this level of enrollment will mean that the study is powered at well over 90% for both the patient reported outcome, primary endpoint for US regulators, as well as for the durable culture conversion primary endpoint for the Japanese health authorities.

重要的是，這一水平的招募意味著該研究對於患者報告的結果、美國監管機構的主要終點以及日本衛生當局的持久文化轉變的主要終點均具有超過 90% 的效力。

We plan to meet with the FDI, this quarter to discuss the possibility of an accelerated filing under subpart H using the successful Phase 3 ARISE trial data. As we have previously mentioned, we deal the most likely pathway to a potential label expansion for ARIKAYCE will require the full data set from the ongoing ENCORE trial which remains on schedule to read out in the first quarter of 2026.

我們計劃本季與 FDI 會面，討論使用成功的第 3 階段 ARISE 試驗數據根據 H 分項加速申請的可能性。正如我們之前提到的，我們認為 ARIKAYCE 潛在標籤擴展的最可能途徑將需要正在進行的 ENCORE 試驗的完整數據集，該試驗仍計劃於 2026 年第一季讀出結果。

Finally let me provide an update on TPIP. Last quarter, I was excited to report that enrollment in our Phase 2 study of patients with PAH had accelerated and that we had passed 75% of the target enrollment as of that date. Today, I'm equally pleased to share that this momentum has continued. As of last week, we had enrolled more than 90% of the target for this trial, keeping us firmly on track to report the top line results in the second half of 2025.

最後，讓我提供一下有關TPIP的最新進展。上個季度，我很高興地報告，我們針對 PAH 患者的第 2 階段研究的招募速度已經加快，截至該日期，我們已完成了目標招募人數的 75％。今天，我同樣高興地告訴大家，這股勢頭仍然持續著。截至上週，我們已招募了本次試驗目標的 90% 以上，這讓我們預計在 2025 年下半年報告營收結果。

And PH-ILD, we expect to present the full results from our Phase 2 study which had a top line readout in May of this year in early 2025 at the Pulmonary Vascular Research Institute's 2025 Annual World Congress in Rio de Janeiro. We look forward to sharing those details then.

PH-ILD，我們預計將在 2025 年初於裡約熱內盧舉行的肺血管研究所 2025 年世界年度大會上展示我們第 2 階段研究的全部結果，該研究在今年 5 月進行了頂線讀數。我們期待屆時分享這些細節。

We're also working to optimize the manufacturing of TPIP so that higher doses can be delivered using the same quantity of dry powder as lower doses. This improved delivery which would allow patients to take doses up to 640 micrograms in a single capsule is how we expect TPIP to be offered in a commercial setting presuming clinical and regulatory success.

我們也致力於優化 TPIP 的生產，以便使用與低劑量相同數量的乾粉來傳遞高劑量。這種改進的給藥方式將允許患者在一粒膠囊中服用高達 640 微克的劑量，我們預計 TPIP 將在臨床和監管成功的情況下在商業環境中提供。

We are doing this work now so that our Phase 3 program can be conducted using that same commercial ready product which would be required for a potential future NDA filing. We remain on track to kick off that Phase 3 program for TPIP in patients with PH-ILD using these optimized doses in the second half of 2025.

我們現在正在進行這項工作，以便我們的第 3 階段計劃能夠使用相同的商業化產品進行，這對於未來可能的 NDA 申請是必需的。我們仍計劃在 2025 年下半年使用這些最佳化劑量啟動針對 PH-ILD 患者的 TPIP 第 3 階段計畫。

In summary, I couldn't be more pleased with where we are as an organization. I am proud of how we have been able to maintain and strengthen Insmed's culture during an unprecedented period of growth for the company. Last week, we announced that we were ranked as the number one employer in science's annual top survey of top employers for the fourth consecutive year. The only other company in the history of this survey to have earned this honor at least four years in a row was Genentech.

總而言之，我對於我們組織的現狀感到非常滿意。我為我們能夠在公司前所未有的發展時期維護和加強 Insmed 的文化而感到自豪。上週，我們宣布，我們連續第四年在《科學》雜誌的年度最佳雇主調查中被評為第一雇主。在本次調查歷史上，唯一另外一家連續至少四年獲此殊榮的公司是基因泰克 (Genentech)。

This external recognition validates what I see every day, which is that even as we transform as an organization, we remain grounded in our core values. The consistent progress that I have seen to date across the company, both operationally and culturally only adds to my confidence in the future of Insmed.

這種外部認可證實了我每天所看到的事實，那就是即使我們作為一個組織發生轉型，我們仍然堅持我們的核心價值。到目前為止，我看到整個公司在營運和文化方面都取得了持續的進步，這更加增強了我對 Insmed 未來的信心。

For most companies in our field, any one of the opportunities in our late stage pipeline from the potential ARIKAYCE label expansion to the potential launch of a product representing a promising new mechanism of action like brensocatib to the chance to develop a potentially paradigm shifting medicine like TPIP would represent the single most exciting opportunity of the organization.

對於我們這個領域的大多數公司來說，我們後期研發線中的任何一個機會，從潛在的 ARIKAYCE 標籤擴展，到可能推出代表有前途的新作用機制的產品（如 brensocatib），再到開發可能改變範式的藥物（如 TPIP）的機會，都代表著組織最激動人心的機會。

At Insmed, we not only find ourselves in the rare position to execute on all three of these programs at once, but I'm also proud to say that we are three for three so far with each program having already demonstrated meaningful clinical success. We take the responsibility to deliver these therapies to patients very seriously and we are committed to following through on these promises.

在 Insmed，我們不僅發現自己處於可以同時執行這三個項目的罕見位置，而且我很自豪地說，到目前為止，我們已經完成了三個項目，每個項目都已經取得了有意義的臨床成功。我們非常重視向患者提供這些療法的責任，並致力於履行這些承諾。

I'll now turn it over to Sara, who will walk us through this quarter's financial results.

現在我將把時間交給 Sara，她將向我們介紹本季的財務表現。

Thank you Will and good morning, everyone. I want to start with a few words about the strength of our financial position. When I last spoke to you in August, Insmed was in a very secure position financially. I am happy to share that today, we are in an even better position due to the deliberate steps taken in the past quarter to strengthen our balance sheet.

謝謝威爾，大家早安。首先我想談談我們的財務狀況。當我八月最後一次與您交談時，Insmed 的財務狀況非常穩定。我很高興地告訴大家，由於上個季度我們採取了一系列措施來加強資產負債表，今天我們的狀況變得更加良好。

These actions include calling our 2025 convertible debt opportunistically utilizing our at the market equity offering program and restructuring our existing term loan. Let me provide you some details on each of these activities.

這些行動包括利用我們的市場股票發行計劃適時贖回我們的 2025 年可轉換債務，並重組我們現有的定期貸款。讓我向您提供有關每項活動的一些詳細資訊。

As discussed on last quarter's earnings call in August, we called our $225 million convertible notes which were set to mature in 2025 and issued approximately 5.7 million shares of stock to note holders which simultaneously lowered our ongoing interest expense burden while also improving our debt to equity ratio. Additionally, in the third quarter, we utilized our ATM to raise approximately $371 million in net proceeds at an average sales price of $75.64 per share. As a reminder during our most recent follow on offering in May, the sale price was $51.50 per share.

正如 8 月上一季的財報電話會議上所討論的那樣，我們贖回了原定於 2025 年到期的價值 2.25 億美元的可轉換票據，並向票據持有人發行了約 570 萬股股票，這同時降低了我們持續的利息支出負擔，同時也改善了我們的債務權益比率。此外，在第三季度，我們利用 ATM 以每股 75.64 美元的平均銷售價格籌集了約 3.71 億美元的淨收益。提醒一下，在我們 5 月最近一次的後續發行中，發行價格為每股 51.50 美元。

Finally, as announced this morning, we were able to successfully restructure our $350 million term loan with Pharmakon. As a reminder, the loan previously carried a variable interest rate based on the SOFR rate plus 7.75% which normally put our actual rate paid in the low to mid teens and was set to mature in 2027. Under the terms of the restructured agreement, Pharmakon will provide us an additional $150 million in proceeds to be received in the fourth quarter.

最後，正如今天早上宣布的那樣，我們成功地重組了與 Pharmakon 的 3.5 億美元定期貸款。提醒一下，該貸款先前採用的浮動利率是基於 SOFR 利率加上 7.75%，這通常使我們的實際支付利率處於 15% 到 20% 之間，並且將於 2027 年到期。根據重組協議的條款，Pharmakon 將向我們提供額外的 1.5 億美元收益，將於第四季度收到。

Importantly, the interest rate on the full principal amount was lowered to a fixed single digit rate of 9.6%. In addition, the maturity for the loan was pushed out to 2029 which is important because we anticipate that our cash inflows from operations during the latter part of the decade would easily support repayment of the loan balance.

重要的是，全額本金的利率下調至9.6%的固定個位數利率。此外，貸款到期日被推遲至 2029 年，這很重要，因為我們預計本世紀後半葉的經營活動現金流入將輕鬆支持償還貸款餘額。

As a result of these actions, our cost of capital is being reduced while our cash runway is being lengthened. As of the end of the third quarter, we had approximately $1.5 billion of cash, cash equivalents and marketable securities on our balance sheet, which represents an increase of approximately $221 million since the end of the second quarter.

由於這些行動，我們的資本成本正在降低，同時我們的現金流量正在延長。截至第三季末，我們的資產負債表上擁有約 15 億美元的現金、現金等價物和有價證券，自第二季末以來增加了約 2.21 億美元。

As a reminder, the current quarter's cash balance does not reflect the additional $150 million of proceeds from the Pharmakon term loan previously discussed and will be reflected in the fourth quarter's financial statements.

提醒一下，本季的現金餘額並未反映先前討論過的 Pharmakon 定期貸款的額外 1.5 億美元收益，並將反映在第四季度的財務報表中。

Net of cash inflows related to the ATM as well as the impact of stock option exercises, our underlying cash burn in the third quarter was approximately $166 million which as expected was somewhat higher than recent quarters.

在扣除與 ATM 相關的現金流入以及股票選擇權行使的影響後，我們第三季的基本現金消耗約為 1.66 億美元，如預期的那樣，略高於最近幾季。

A portion of this increase is related to the $12.5 million cash milestone payment made to AstraZeneca this quarter, which resulted from the announcement of our intention to file for the approval of brensocatibfor the treatment of patients with bronchiectasis. The remainder of the increase is due to higher headcount in other expenses related to ongoing preparations for the potential launch of brensocatib.

該增長部分與本季度向阿斯特捷利康支付的 1,250 萬美元現金里程碑付款有關，這筆付款源於我們宣布有意申請批准 brensocatib 用於治療支氣管擴張患者。其餘成長部分是由於與 brensocatib 的潛在上市持續準備相關的其他費用和人員編制增加。

As a result, we expect our underlying cash burn to increase compared to historical levels between now and the time that brenso begins contributing revenue assuming regulatory approval and commercialization.

因此，我們預計，從現在到 brenso 在獲得監管部門批准和商業化之後開始貢獻收入期間，我們的潛在現金消耗將比歷史水準增加。

Before I move on, I would like to address the subject of profitability, as I appreciate, this is an important topic for many of our shareholders. We do not yet have sufficient cash on hand to fund our business until it becomes profitable on its own, but we continue to be mindful of reaching our ambition of becoming a self sustaining biotech company. Given our progress this quarter, we are now in a position in which we can be patient and flexible as we think about our future financing needs.

在繼續之前，我想談談獲利能力的問題，因為我知道這對我們的許多股東來說是一個重要的主題。我們手頭上還沒有足夠的現金來資助我們的業務直到它自己盈利，但我們將繼續牢記實現成為一家自給自足的生物科技公司的雄心壯志。鑑於本季的進展，我們現在可以耐心且靈活地考慮未來的融資需求。

I will now walk you through the highlights of our commercial performance in the third quarter of 2024. Global net revenues, this quarter was $93.4 million reflecting 18% year-over-year growth compared to the third quarter of 2023. This represents the highest quarterly sales for ARIKAYCE in its history and the second quarter in a row in which we have set a new record for global sales.

現在，我將向大家介紹我們 2024 年第三季商業表現的亮點。本季全球淨收入為 9,340 萬美元，與 2023 年第三季相比年增 18%。這是 ARIKAYCE 史上最高的季度銷售額，也是我們連續第二季創下全球銷售新紀錄。

In the US, net revenue was $66.9 million up 13% compared to the prior year period. This growth was driven by continued strength in new patient starts reflecting the volume driven growth we continue to see for ARIKAYCE.

在美國，淨收入為 6,690 萬美元，比去年同期成長 13%。這一增長是由新患者數量持續強勁增長所推動的，反映了我們繼續看到的 ARIKAYCE 的數量驅動增長。

In Japan net revenue is $21 million up 31% compared to the prior year period. This performance was driven by higher new patient starts and a strong treatment continuation rate amongst existing patients. In Europe, and the rest of the world, net revenue was $5.6 million up 45% compared to prior year period driven primarily by continued strength in Germany and the UK.

日本的淨收入為 2,100 萬美元，比去年同期成長 31%。這一業績得益於新患者數量的增加和現有患者治療持續率的提高。在歐洲和世界其他地區，淨收入為 560 萬美元，比去年同期成長 45%，主要得益於德國和英國持續強勁的成長動能。

Importantly, this quarter's performance keeps us on track to achieve our full year 2024 global revenue guidance of $340 million to $360 million. Let me now turn to a few additional financial items.

重要的是，本季的表現使我們有望實現 2024 年全年全球收入預期 3.4 億至 3.6 億美元。現在讓我來談談幾個另外的財務項目。

Our US gross to nets this quarter were 14.2% which was consistent with our expectations, we continue to anticipate that gross to nets will settle in the mid to high teens for full year 2024. Cost of product revenues for the third quarter of 2024 was $21.2 million or 22.7% of revenues, which is consistent with our historical performance.

本季美國毛利率與淨利率比率為 14.2%，與我們的預期一致，我們繼續預期 2024 年全年毛利率與淨利率比率將穩定在 15% 至 20% 之間。2024 年第三季的產品收入成本為 2,120 萬美元，佔營收的 22.7%，與我們的歷史表現一致。

Research and development expenses in the third quarter were $150.8 million and SG&A expenses were $118.9 million, reflecting continued investment in our early and mid to late stage pipelines as well as investments in brensocatib commercial readiness initiatives.

第三季的研發費用為 1.508 億美元，銷售、一般及行政費用為 1.189 億美元，反映了我們對早期、中後期產品線的持續投資以及對 brensocatib 商業準備計劃的投資。

In closing Insmed currently finds itself in a unique position of strength both financially and operationally. We produced record setting revenue in the third quarter, keeping us on track to deliver on our full year guidance.

最後，Insmed 目前在財務和營運方面都處於獨特的優勢地位。我們在第三季創造了創紀錄的收入，使我們有望實現全年目標。

Additionally, we have approximately $1.5 billion of cash, cash equivalents and marketable securities on our balance sheet which allows us to comfortably fund our operations as we enter this transformational period ahead, one in which we anticipate the launch of brensocatib as well as additional, meaningful mid to late stage data readouts from across our portfolio.

此外，我們的資產負債表上還有大約15億美元的現金、現金等價物和有價證券，這使我們能夠在未來進入轉型時期時輕鬆地為我們的營運提供資金，我們預計將在此時期推出 brensocatib，以及從我們的投資組合中獲得更多有意義的中後期數據。

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

我們現在想開始回答你們的問題。珍妮，我們可以回答第一個問題嗎？

(Operator Instructions)

（操作員指令）

Joe Schwartz, Leerink Partner.

Joe Schwartz，Leerink 合夥人。

Hi, thanks so much and congrats on the progress. I was wondering first if you could talk some more about the expanded sales force in terms of how effective it can be in launching brensocatib based on its size and focus as well as how much the disease state awareness activities can help you prepare for launch and whether you've looked at analyst estimates for brensocatib sales early on and is there anything we should keep in mind as we model the ramp?

你好，非常感謝，並祝賀你的進展。我想知道，首先您是否可以進一步談談擴大銷售隊伍的情況，根據其規模和重點，它在推出 brensocatib 方面能有多有效，以及疾病狀態意識活動在多大程度上幫助您為發佈做好準備，以及您是否早期就研究過分析師對 brensocatib 銷售的估計，以及我們在模擬增長時應該記住什麼？

So, thanks for the question, Joe. I mean, I think I would tell you, I've had the pleasure of spending some time with the people that we brought on board and they have two general dimensions that I think are worth noting, the first is they are a very experienced group of people, they have done multiple launches, we've got a lot of multiple presidents club winners in this group, I always like to remind folks that we had more than 7,000 resumes for 120 positions. So it just speaks to the volume of interest that existed for these roles.

所以，謝謝你的提問，喬。我的意思是，我想我會告訴你，我很高興能與我們招募的人共度一段時光，我認為他們有兩個值得注意的總體方面，首先，他們是一群非常有經驗的人，他們已經多次發布產品，我們這個團隊中有很多多次總裁俱樂部獲獎者，我總是想提醒大家，我們有超過 7,000 份簡歷職位競爭 120 個簡歷職位。所以這只是說明了人們對這些角色的興趣程度。

So we really got the best of the best and I would tell you in on heart, I think I would match this sales force against any in the industry and feel like we're going to come out ahead. The second point about these people is that they are an excellent cultural fit, to a person, they are focused on patients and delivering for those patients and that's an incredibly important part of our culture as you know.

因此，我們確實擁有最優秀的人才，我可以真心地告訴你們，我認為我們可以將這支銷售隊伍與業內任何一支銷售隊伍進行比較，並且感覺我們會勝出。關於這些人的第二點是，他們與我們的文化非常契合，就個人而言，他們專注於患者並為患者提供服務，正如你所知，這是我們文化中非常重要的一部分。

As we think about the actual launch itself and what this empowers us to do, as I mentioned, we literally have the ability to call on every pulmonologist in the United States with this kind of capacity, and importantly, as we think about what they're doing right now because as we said, as of October 1, they're in the field, fully trained, both calling about ARIKAYCE, but also doing disease state awareness about bronchiectasis.

當我們考慮實際的啟動本身以及這將賦予我們什麼能力時，正如我提到的那樣，我們實際上有能力召集美國每一位具有這種能力的肺病專家，重要的是，當我們考慮他們現在正在做什麼時，因為正如我們所說的那樣，截至 10 月 1 日，他們已經在該領域接受了全面培訓，既呼叫 ARIKAYCE，也進行有關支氣管擴張的疾病狀態。

And that is a model that may bring familiar to you because it is the exact same approach we took when we launched ARIKAYCE. ARIKAYCE is you'll remember the street had us doing about 40 million to 60 million in the first year and we ended up doing more than 130. And that's an indication of what this kind of early stage education and relationship building can provide by way of uptake of medicine when the medicine is clearly a benefit to patients. So I couldn't be more excited about the group we've assembled and yeah, I think, you're going to see really first in class -- best in class performance.

這個模型可能會讓您感到很熟悉，因為它與我們推出 ARIKAYCE 時採用的方法完全相同。ARIKAYCE 你會記得，第一年我們的街道收入約為 4000 萬到 6000 萬美元，而最終我們的收入超過了 13000 萬美元。這表明，當藥物顯然對患者有益時，這種早期教育和關係建立可以透過藥物的吸收來發揮作用。所以我對我們組建的這個團隊感到無比興奮，是的，我認為，你將會看到真正的班上第一名——班上最好的表現。

Okay. Thanks. And then does the aforementioned expected price range for brenso refer to the 10 milligram dose, the 25 milligram dose or both. I'm just wondering how you're thinking about whether it makes sense to use flat or graduated pricing, for example, do payers appreciate the added value that the 25 milligrams dose provides.

好的。謝謝。那麼，上述 brenso 的預期價格範圍是指 10 毫克劑量、25 毫克劑量還是兩者兼而有之。我只是想知道您如何考慮使用固定定價或分級定價是否合理，例如，付款人是否欣賞 25 毫克劑量所提供的附加價值。

So, we haven't made any decisions on pricing yet. It's going to be a long time before we do. But I would tell you that we think the objective here in all our clinical studies is to understand what the medicine can do and that forms the basis of the value proposition. I do want to come back to your comment about -- earlier about what we might expect in the first year. I don't know Sara if you want to take that one.

所以，我們還沒有對定價做出任何決定。我們還需要很長時間才能實現這一目標。但我想告訴你，我們認為所有臨床研究的目標都是了解藥物的作用，這構成了價值主張的基礎。我確實想回到你之前關於我們在第一年可能期待什麼的評論。我不知道薩拉你是否想接受這個。

Sure. Joe, thanks for the question specifically on the analyst expectations. And while we obviously haven't provided near term guidance for brensocatib, what we have said is we believe brensocatib, the non bronchiactisis alone is a $5 million plus peak sales opportunity, So a tremendous opportunity from a value creating perspective as well as impact on patients.

當然。喬，感謝您特別提出有關分析師預期的問題。雖然我們顯然沒有為 brensocatib 提供近期指導，但我們說過，我們相信 brensocatib 僅非支氣管擴張治療就是一個 500 萬美元以上的高峰銷售機會，因此從創造價值的角度以及對患者的影響來看，這是一個巨大的機會。

What I would point you to is some analogs in the industry, you know, we study a lot of precedent here in Insmed, and so if you look at some of the first in class, best in class launches in the respiratory space like DUPIXENT, FASENRA, TEZSPIRE, OFEV, you see in their first two quarters of launch, they put high double digit millions in revenue, and then if you kind of carry that forward in the next four quarters of launch, it's about $500 million to $600 million, I think the best with DUPI was about $700 million.

我想指出的是行業中的一些類似物，您知道，我們在 Insmed 研究了很多先例，因此，如果您看看呼吸領域中的一些同類首創、最佳產品，例如 DUPIXENT、FASENRA、TEZSPIRE、OFEV，您會發現在推出後的前兩個季度，他們的收入高達數百萬美元，然後，如果您將其 40 億美元

So very significant revenue numbers, and while I can't comment on specifically what the shape of the brensocatib will look like these are best in class launches, and I think analogs that any company would strive to even come close to.

因此，收入數字非常可觀，儘管我無法具體評論 brensocatib 的形態，但這些是同類產品中最好的，我認為任何公司都會努力接近。

Thanks for all the helpful color.

感謝所有有用的顏色。

Jessica Fye, JPMorgan.

摩根大通的傑西卡·菲伊 (Jessica Fye)。

Hey, guys, good morning. Thanks for taking my questions. I wanted to ask on TPIP. For PH-ILD, can you talk a little bit more about what needs to happen between now and the commencement of that Phase 3trial in the back half of next year? Is it that manufacturing work you referenced? And if so, can you expand a little bit on what specifically is happening there? And then can you also talk about how you think about the enrollment timing for the Phase 3in PH-ILD?

嘿，大家早安。感謝您回答我的問題。我想問一下TPIP。對於 PH-ILD，您能否再談談從現在到明年下半年開始第三階段試驗之間需要發生什麼？這就是您所提到的製造業工作嗎？如果是的話，您能否稍微詳細說明一下那裡具體發生了什麼？然後您可以談談您對 PH-ILD 第 3 階段的招生時間的看法嗎？

Should we use the increased trial enrollment as a guide? Does the increased awareness with Tyvaso's strong launch in that setting help you? Or is it a headwind to enrollment to have an approved drug in the space? So like, would you look to enroll in the ex US as a result of that?

我們是否應該以增加的試驗入學人數作為指引？Tyvaso 在這種環境下強勢推出後知名度的提高對您有幫助嗎？或者說，這對於在該領域獲得藥物批准而言是一個阻力嗎？那麼，您是否會考慮在美國以外地區註冊？

Just trying to kind of understand from what it's going to take to kick that study off and then how to think about enrollment once it does start.

只是想了解啟動這項研究需要什麼，以及研究開始後如何考慮招生。

Yeah, sure. So thanks for the questions. I think the first thing I would say about TPIP is it's probably the most underappreciated asset in our portfolio. I'm really excited about what I think this drug already has shown and what I think it will show when we look at the Phase 2 data in PAH next year. We do intend to move forward into Phase 3for PH-ILD.

是的，當然。感謝您的提問。關於TPIP，我想說的第一件事是它可能是我們投資組合中最被低估的資產。我對這種藥物已經展現出的成果以及明年我們在 PAH 的第二階段數據中將會展現出的成果感到非常興奮。我們確實打算進入 PH-ILD 的第 3 階段。

We have a lot of the work for that already ongoing. The second half of next year as a target for kicking that off is really driven by both the preparation for wanting that trial to go particularly well, wanting to ensure that our dialogue with FDA clarifies the approval pathway for Phase 3, i.e., 1 versus 2 Phase 3 studies. Our expectation is we'll only need one, but we have to confirm that. And then I would say, finally, and most importantly, the work being done in manufacturing, which is sort of being done in parallel to all this. Specifically, what we want is to make this very easy for patients.

我們已在進行大量這方面的工作。以明年下半年為啟動目標，實際上是出於兩方面的考慮：一是希望試驗能夠順利進行，二是希望確保我們與 FDA 的對話能夠明確第 3 階段的批准途徑，即第 1 階段與第 2 階段的第 3 階段研究。我們的預期是只需要一個，但我們必須確認這一點。最後我想說，最重要的是，製造業的工作是與這一切同時進行的。具體來說，我們希望讓患者能夠輕鬆完成這項過程。

And so regardless of how much drug they intend to or need to take, we'd like it to be one capsule. And so if you're going to go up as high as 640 micrograms, remember that, that's a really high dose relative to what people are able to get to now. To be able to do that also with a single capsule makes it supremely easy to take and just smooths the utilization of the drug. So that's the thought there. And it is the merger of all of those different forces that is shaping the launch timing for the drug.

因此，無論他們打算或需要服用多少藥物，我們都希望是一顆膠囊。因此，如果要將劑量提高到 640 微克，請記住，相對於人們現在能夠達到的劑量，這是一個非常高的劑量。只需一粒膠囊就能達到這一效果，這使得服用變得極其容易，並使藥物的使用更加平穩。這就是我的想法。正是所有這些不同力量的融合決定了該藥物的上市時間。

We think about enrollment, we're always frustrated in the PAH space generally because these are difficult trials to enroll. These patients are very sick. In a sense, we're in a little bit better position when we start PH-ILD and when we look at PAH in Phase 3 as well because the competitive landscape of other trials will have decreased in its density by that time. So I couldn't be more excited about this. I'm really excited to see the PAH data in the second half of next year and also to kick off the ILD Phase 3.

我們考慮招募，我們在 PAH 領域總是感到沮喪，因為這些試驗很難招募。這些病人病情非常嚴重。從某種意義上說，當我們開始 PH-ILD 以及在第 3 階段研究 PAH 時，我們處於更有利的地位，因為到那時其他試驗的競爭格局的密度將會降低。所以我對此感到非常興奮。我非常高興看到明年下半年的 PAH 數據，並啟動 ILD 第三階段。

Hopefully, that answers your question.

希望這能回答您的問題。

Thank you.

謝謝。

Vamil Divan, Guggenheim Securities.

古根漢證券的 Vamil Divan。

Hi, This is [Dan] today on for Vamil. So we've been receiving some investor questions this morning around the general financial position with the Pharmakon term loan amended, and it seems that you raised some additional money through the ATM. So I was wondering if maybe you could talk more generally about your financial position now and your plans going forward as you prepare for the brenso launch next year. Thanks

大家好，我是今天為 Vamil 節目的 [Dan]。今天早上我們收到了一些投資者的問題，關於 Pharmakon 定期貸款修改後的整體財務狀況，而且似乎您透過 ATM 籌集了一些額外的資金。所以我想知道您是否可以更全面地談談您目前的財務狀況，以及在為明年的 brenso 發射做準備時未來的計劃。謝謝

Yeah, you bet. I'm going to turn it over to Sara in a minute. But I got to just open up by telling you, I could not be happier about the breadth and depth of the strength of our balance sheet improvement this last quarter. We are now in a very strong financial position to take on the breadth of opportunities this company has, and we happen to be hitting on all cylinders, both in terms of commercial, clinical development and preparation for next commercial launch. This resourcing is going to be helpful to that cause.

是的，確實如此。我馬上就把它交給薩拉。但我必須要坦白地告訴你們，我對上個季度我們的資產負債表在廣度和深度上的強勁改善感到非常高興。我們現在的財務狀況非常強勁，可以抓住公司面臨的眾多機遇，而且我們在商業、臨床開發和下一次商業發布的準備方面都全力以赴。這些資源將會對這項事業有所幫助。

But Sara, maybe you want to talk about it.

但是薩拉，也許你想談論它。

Yeah, absolutely. Really appreciate the question. Just on the onset, Insmed is in the strongest financial position it's ever been since I've been at the company and probably since the company's history and could not be more proud of the achievements of everyone part of the Insmed family and all the support that we continue to get from all of our partners, shareholders, noteholders, debt holders. A couple of comments specifically on the actions that we took. Specifically on the ATM, that is an opportunistic tool that pretty much every biotech company has that is not at a profitable level.

是的，絕對是如此。非常感謝您的提問。自從我加入公司以來，甚至可能是公司成立以來，Insmed 的財務狀況一直處於最強勁的狀態，我為 Insmed 家族中每個成員所取得的成就以及我們繼續從所有合作夥伴、股東、票據持有人、債權人那裡獲得的所有支持感到無比自豪。針對我們所採取的行動，我提出幾點評論。特別是 ATM，這是幾乎每家生物科技公司都擁有的機會主義工具，但其獲利水準尚未達到。

We used that in a small amount. It was about 2% of our overall market cap over the period of time. But I think the most important piece there is our focus on dilution and being sensitive to dilution for shareholders. And as we think about the raise that we did earlier this year and the utilization of the ATM, the ATM average price was almost a 50% premium to our last raise. So we were very cognizant of dilution, pricing as well as during the time of trading on the ATM, our stock price actually went up.

我們用了少量的這個。它約占我們這段時間內總市值的 2%。但我認為最重要的是我們專注於稀釋並對股東的稀釋保持敏感。當我們考慮今年稍早的加價以及 ATM 的利用率時，我們發現 ATM 的平均價格比上次加價高出了近 50%。因此，我們非常清楚稀釋、定價以及在 ATM 上交易期間，我們的股價實際上上漲了。

So we were very careful on that. On the Pharmakon restructure, I couldn't be more pleased that Pharmakon was willing to put additional monies and to push out the payment. A couple of, I think, really important pieces there. By being able to get a fixed interest rate and being able to lower it into single digits, our interest burden on the company essentially remains the same, and we have additional capital now, and we will now have the benefit of having the brenso launch and need to pay back that principal amount towards the latter part of the decade. So could not be more pleased with where we are financially, and we are now in a position where we want to be able to resource appropriately the brensocatib launch.

因此我們對此非常小心。關於 Pharmakon 重組，我非常高興 Pharmakon 願意投入額外資金並推遲付款。我認為，其中有幾點非常重要。透過能夠獲得固定利率，並且能夠將其降低至個位數，我們公司的利息負擔基本上保持不變，而且我們現在擁有額外的資本，並且我們現在將受益於 brenso 的推出，並需要在 2020 年前後償還本金。因此，我們對於自己的財務狀況感到非常滿意，現在我們希望能夠為 brensocatib 的推出提供適當的資源。

This is a once in sort of a lifetime type of launch that we have the opportunity to be part of and the capital that we now have on our balance sheet will allow us to appropriately resource that program. Thank you.

這是一次千載難逢的發布，我們有機會參與其中，而我們目前資產負債表上的資本將使我們能夠為該計劃提供適當的資源。謝謝。

Great. Thank you.

偉大的。謝謝。

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

Hi everyone. This is [Nicole] on the line for Ritu. Thank you so much for taking my question. So I was hoping to get some initial or additional color on labeling language that you expect for brensocatib. Do you think it's going to be more broad with just treatment of bronchiectasis? Or do you think there might be some more specific language about the reduction of the exacerbations? And then a quick second follow-up question is, are you planning on including adolescents in the labeling as well? Thank you.

大家好。我是 [Nicole]，負責 Ritu 的工作。非常感謝您回答我的問題。因此，我希望獲得一些關於您期望的 brensocatib 標籤語言的初步或額外說明。您認為僅治療支氣管擴張的治療範圍會更廣嗎？或者您認為可能有一些關於減少病情惡化的更具體的語言嗎？然後第二個後續問題是，您是否計劃將青少年也納入標籤範圍？謝謝。

So I'm going to actually ask Martina to take that on first.

所以我其實要先請 Martina 來承擔這個任務。

Yeah. Hi, Nicole. So yeah, we do expect a broad label language, and that would be for non -- bronchiectasis. We also will ask for adolescent patients. They have been part of the trial. It depends on what the FDA's judgment will be on that, but we expect a broad label language. And usually, the label language doesn't specify your inclusion or exclusion criteria. It speaks to the indication.

是的。你好，妮可。是的，我們確實期待一種廣泛的標籤語言，這將適用於非支氣管擴張症。我們也會詢問青少年患者。他們已經參與了審判。這取決於 FDA 對此的判斷，但我們期待標籤語言的廣泛性。通常，標籤語言不會指定您的納入或排除標準。這說明了這一跡象。

Yeah. The only comment I would add to that is that, of course, there's different audiences we have to impress. One of them is the FDA, the other is market access. Market access is the one that's going to be a little bit more focused on whether or not the patient has had two or more exacerbations consistent with our label.

是的。我唯一想補充的是，當然，我們必須給不同的觀眾留下深刻印象。其中一個是FDA，另一個是市場准入。市場准入將更加關注患者是否曾兩次或兩次以上與我們的標籤相符的病情惡化。

So while the FDA label language will probably be broad, the market access, at least in initial interaction is probably going to be a little more focused around those two prior exacerbations, and we're hoping to accomplish that through attestation, but that will, of course, come closer to the time of launch.

因此，儘管 FDA 標籤語言可能很廣泛，但市場准入，至少在最初的互動中可能將更多地集中在之前的兩次惡化上，我們希望透過證明來實現這一點，但這當然會更接近發佈時間。

Thank you.

謝謝。

Nicole Germino, Truist Securities.

Truist Securities 的 Nicole Germino。

Good morning. Thanks for taking my question. Excuse me. We're getting questions around CRS without nasal polyps and potentially -- and it could potentially be as big as bronchiectasis given the potential benefit in steroid nonresponders patients requiring surgery. So how many of those patients are seeking additional therapies beyond standard of care or getting repeat surgeries? And can you help us understand how big this opportunity is? And how big could it be? And will it be focused towards ENT broadly or ENT surgical specialists? It seems like a very small focus, but wanted to get your thoughts.

早安.感謝您回答我的問題。打擾一下。我們收到了有關不伴有鼻息肉的慢性鼻竇炎 (CRS) 的問題，並且可能——考慮到對需要手術的類固醇無反應患者的潛在益處，它可能與支氣管擴張一樣嚴重。那麼，有多少患者正在尋求標準治療以外的其他療法或接受重複手術？您能幫助我們了解這個機會有多大嗎？它能有多大？其主要針對的是耳鼻喉科還是耳鼻喉科專家？這似乎是一個非常小的焦點，但我想聽聽你的想法。

Yeah. So I appreciate the question. I think you are right to perceive CRS without nasal polyps as a very, very substantial opportunity. Just to remind everybody, this is a patient population in the US alone that numbers more than 26 million people, currently, without anything approved to treat it.

是的。我很感謝你提出這個問題。我認為您正確地認識到不伴隨鼻息肉的慢性鼻竇炎是一個非常非常好的機會。需要提醒大家的是，光是在美國，這種疾病患者人數就超過 2,600 萬人，目前還沒有任何藥物可以治療這種疾病。

Now when we approach a disease state of that magnitude, we look for the sickest patients, and we look for our medicine to have the most material impact on them. And in that group, we sort of focus on for our initial foray. We've talked about how that is an incidence rate of about 400,000 patients a year, so not a prevalence, but an incidence, that's that number of patients coming in that are broadly defined as being eligible for surgery or having had repeat surgeries at a severity point that would justify the use of this medicine.

現在，當我們面對如此嚴重的疾病狀態時，我們會尋找病情最嚴重的患者，並尋求我們的藥物對他們產生最實質的影響。在這個小組中，我們主要專注於進行我們的初步嘗試。我們已經討論過，每年的發病率約為 40 萬名患者，所以這不是患病率，而是發病率，即廣義上定義為有資格接受手術或已經重複手術且病情嚴重到可以使用這種藥物的患者人數。

It may get bigger than that, but I would just start there to sort of understand the broad opportunity that this market would represent. And next year, we're going to have a very clear understanding of whether our drug is going to be impactful on these patients with the readout of the Phase 2 study.

它可能會變得更大，但我只會從那裡開始了解這個市場將代表的廣泛機會。明年，透過第二階段研究的結果，我們將非常清楚地了解我們的藥物是否對這些患者產生影響。

So I think this is -- you're going to hear a lot more about this indication once we know our ability to impact it, and we understand the profile of patients within the study and the nuances of what the medicine does. Remember that we're testing both 10 milligrams and 40 milligrams in this study. So that's also a distinction from what we did in bronchiectasis, where we had 10 milligrams and 25 milligrams. Overall, super excited about that program and a lot more to come in terms of specificity.

所以我認為，一旦我們知道了我們影響它的能力，並且我們了解了研究中的患者概況以及藥物作用的細微差別，你就會聽到更多關於這種適應症的信息。請記住，我們在這項研究中測試了 10 毫克和 40 毫克。所以這也與我們在支氣管擴張症中所做的處理有區別，我們在治療支氣管擴張症時使用的劑量是 10 毫克和 25 毫克。總的來說，我對該計劃感到非常興奮，並且在具體細節方面還有很多未來可言。

Thanks so much. And one quick follow-up. For brensocatib and bronchiectasis, can you confirm if both doses are going to be filed? Or how -- what can you share?

非常感謝。還有一個快速的後續行動。對於 brensocatib 和支氣管擴張症，您能否確認是否要提交兩劑藥物？或者如何—您可以分享什麼？

Yeah. So our intention is to file the data from both doses. As we've talked about before, there's some very interesting details in the 25 milligram secondary endpoints that we find and other KOLs have found particularly compelling. But the ultimate decision about which dose to be selected or both doses to be selected is in the hands of the FDA based on the data that they will review. So we want to provide them all that data. The good news is both doses work. Both are compelling. So whatever the FDA's conclusion is, we'll be in a position to launch commercially, and we'll have more information on that once we've heard from FDA.

是的。因此我們的目的是將兩劑的資料歸檔。正如我們之前談到的，我們發現 25 毫克次要終點中有一些非常有趣的細節，其他 KOL 也發現這些細節特別引人注目。但最終選擇哪種劑量或兩種劑量的決定權都在 FDA 手中，取決於他們審查的數據。所以我們想向他們提供所有數據。好消息是兩種劑量都有效。兩者都很有說服力。因此，無論 FDA 的結論是什麼，我們都將能夠進行商業化推廣，一旦我們收到 FDA 的答复，我們將獲得更多資訊。

Great. Thank you so much.

偉大的。太感謝了。

Jason Zemansky, Bank of America.

美國銀行的傑森·澤曼斯基（Jason Zemansky）。

Good morning, everyone. Congratulations on the quarter and the progress. Thanks for the color on BiRCh. Curious, what are you looking for in terms of efficacy, at least from the sinus total symptom score on the top line to be encouraged about its activity in CRS? And then maybe how translatable are these results to other non-pulmonary indications in your view?

大家早安。恭喜本季並取得的進展。感謝 BiRCh 的色彩。好奇，就療效而言，您正在尋找什麼，至少從頂線的鼻竇總症狀評分來看，可以鼓勵其在 CRS 中的活性？那麼，在您看來，這些結果對其他非肺部疾病的適應症有多大幫助？

Yeah. So I'm going to ask Martina to address that.

是的。因此我要請 Martina 來解決這個問題。

Yeah. Hi Jason. So what we're looking for in CRS is that we're detecting a difference of 1.34 point to 1.55 point. It depends on what treatment effect that we're seeing, but we are 80% powered to show that if it's on that 1.34 point difference. And we do that for an alpha level of 0.05 point. So what you -- if you compare that to the only other treatment really that is right now approved for that, and that is the enhanced spray -- nasal spray, which is basically fluticasone.

是的。嗨，傑森。因此，我們在 CRS 中尋找的是偵測到的 1.34 點到 1.55 點的差異。這取決於我們看到的治療效果，但如果是 1.34 點差異，我們有 80% 的能力證明這一點。我們對 0.05 點的 alpha 水準進行了此操作。所以，如果將其與目前唯一真正批准的其他治療方法進行比較，那就是增強型噴霧劑——鼻噴劑，其基本成分是氟替卡松。

Based on that, they have shown a difference of 1.4 point to 1.9 point, and that was depending on whether these patients had used steroids in addition or not. So I think we're well in that range.

基於此，他們顯示出 1.4 分到 1.9 分的差異，這取決於這些患者是否另外使用了類固醇。所以我認為我們完全處於這個範圍內。

Got it. And I appreciate you haven't shared some of your broader strategies here. But assuming that there is efficacy in both CRS and HS, I mean, what makes an ideal I&I condition to pursue for brenso?

知道了。我很感激您沒有在這裡分享您的一些更廣泛的策略。但假設 CRS 和 HS 都有效，我的意思是，什麼是 brenso 追求的理想 I&I 條件？

Yeah. So I think it's -- those are two distinct diseases, both CRS without nasal polyps as well as HS. And we have to see what we see in both of those indications. The reason we're testing for the 10 milligram and to the 40-milligram dose that in both of these diseases, in a way, we may see that there is an additional benefit coming from a higher dose, reason being that in, for example, HS, there is net formation and can -- when we push down NSPs even further impact that net formation. And the same is true for CRS, both of them are related to the intensity of neutrophil inflammation.

是的。所以我認為 —— 這是兩種不同的疾病，都是不伴隨鼻息肉的 CRS 和 HS。我們必須從這兩個跡像中看出什麼。我們之所以對這兩種疾病分別進行 10 毫克和 40 毫克劑量的測試，在某種程度上，我們可能會發現更高劑量還有額外的好處，原因是，例如，在 HS 中，有淨形成，而且當我們壓低 NSP 時，甚至會進一步影響這種淨形成。CRS也是如此，均與嗜中性球發炎強度有關。

And the only thing I would add to that is, of course, this relates to brensocatib and what we're learning from it. If we take a step back, we think about DPP1 inhibition and its ability to impact neutrophil-mediated diseases. What has been unlocked with the ASPEN study and the WILLOW study and hopefully with BiRCh and CEDAR is this realization that there is broader applicability of this mechanism.

我唯一想補充的是，當然，這與 brensocatib 以及我們從中學到的東西有關。如果我們退一步考慮，我們會思考 DPP1 抑制及其影響嗜中性球介導疾病的能力。ASPEN 研究和 WILLOW 研究以及 BiRCh 和 CEDAR 研究已揭示出此機制具有更廣泛的適用性。

So to that end, after the WILLOW study, we initiated some extensive work in our research labs, and that has been able to produce hundreds of additional DPP1 candidates that we have now refined down to a smaller number and which we intend to bring into the clinic as second-generation DPP1s. You'll be hearing more about this in the coming years, but let me just highlight that one of the indications that we're giving consideration to is rheumatoid arthritis.

為此，在 WILLOW 研究之後，我們在研究實驗室進行了一些廣泛的工作，並且已經能夠生產出數百種額外的 DPP1 候選藥物，現在我們已將它們精煉為更少的數量，並打算將它們作為第二代 DPP1 藥物引入臨床。您將在未來幾年聽到更多關於這方面的消息，但我只想強調一下，我們正在考慮的症狀之一是類風濕性關節炎。

Another one is COPD patients. These would be novel DPP1s that would go through development process, but with our understanding at the beginning that the mechanism is effective in these target populations. Each additional clinical study we complete, we learn more about this mechanism. And I think you are correct to assume that there will be potential applicability of it to many more diseases, and that's why this library of DPP1s is being developed, each which will be hopefully more specifically targeted to the unique features of the disease we're pursuing.

另一個是COPD患者。這些將是需要經歷開發過程的新型 DPP1，但我們一開始就了解該機制對這些目標族群是有效的。我們完成的每項臨床研究都會讓我們對這個機制有更多的了解。我認為您的假設是正確的，它將可能適用於更多疾病，這就是為什麼要開發這個 DPP1 庫，希望每個 DPP1 庫都能更具體地針對我們所研究的疾病的獨特特徵。

Got it. Thank you, Martin and Will for the color.

知道了。感謝馬丁和威爾提供的顏色。

Jennifer Kim, Cantor.

珍妮佛金（Jennifer Kim），領唱。

Hi. Thanks for taking my question. I have one on brenso. Can you remind us what's left for filing and what your confidence is in getting priority review? And then somewhat related, Sara, you pointed to other launches and seeing high double-digit millions in the first two quarters. I think if I look at DUPI in the first full quarter of launch, it was something like high 20s. And based on the timing of filing this being a new drug, it looks to me like this could be more of a July or August launch. Is that something people should also factor into their models? Thanks.

你好。感謝您回答我的問題。我在 brenso 上有一個。您能否提醒我們還有哪些文件需要提交，以及您對獲得優先審查有何信心？然後有些相關的是，Sara，你指出了其他產品的發布，並在前兩個季度看到了數百萬美元的高額銷售額。我認為，如果我看一下推出後第一個完整季度的 DUPI，它大約是 20% 左右。根據提交新藥申請的時間，我認為該藥物可能會在七月或八月上市。人們是否也應該將其考慮進他們的模型中？謝謝。

So the determination of priority review is made by the FDA and their first written response to us. Typically, that is -- that arrives by day 74. So they have their verbal communication around day 60, and then there's a written response that comes on day 74. It's important to understand that until we have that written response in hand, we won't know for sure anything, right? You always want to have it in writing from FDA.

因此，優先審查的決定是由 FDA 做出的，並且他們會給我們第一次書面回應。通常情況下，它會在第 74 天到達。因此他們在第 60 天左右進行口頭交流，然後在第 74 天收到書面回應。我們必須明白，除非我們手邊有書面答复，否則我們無法確定任何事情，對嗎？您總是希望獲得 FDA 的書面證明。

Well, we expect that we will -- and we are on track to file this quarter. So if you do quick math, just take it from the end of the quarter to make it easy and add 74 days, that gives you some sense of when in the first quarter, we'll have a greater understanding. Obviously, once we have that in hand, we will share it with you, and that will hopefully indicate that we have been granted priority review. Nothing is for certain, but our fingers are crossed for that. And that would put the timing somewhere around the middle of the year for launch, assuming everything goes as expected.

嗯，我們預計我們會—而且我們預計在本季度提交文件。因此，如果您進行快速計算，只需從季度末開始取值並添加 74 天，這樣您就可以了解第一季的時間，我們將有更深入的了解。顯然，一旦我們掌握了這些信息，我們就會與您分享，並希望這表明我們已獲得優先審查。沒有什麼是確定的，但我們對此充滿希望。如果一切進展順利，那麼發射時間將定在今年年中左右。

If we don't get priority review, it will be toward the end of the year. Either way, we're going to be ready, and I couldn't be more excited about the -- where we are positioned and how everything is going.

如果我們沒有獲得優先審查，那將是在年底。無論如何，我們都將做好準備，而且我對我們的定位以及一切進展感到無比興奮。

Yeah. And then, Jennifer, specifically on the question of timing, as Will just kind of walked you through the different scenarios from a timing perspective, the analogs that I shared, I won't get into sort of the details on this call around the first quarter of each of those was it a full 3 months? Was it 2 months? But I do think that's something that as folks are building their models, they need to be thoughtful of as they're thinking about revenues for '25 versus '26 for brenso and what that curve looks like.

是的。然後，詹妮弗，具體到時間問題，正如威爾從時間角度向您介紹的不同場景，我所分享的類比，我不會在這次電話會議上詳細介紹每個場景的第一季度，是整整 3 個月嗎？是兩個月嗎？但我確實認為，這是人們在建立模型時需要仔細考慮的問題，因為他們正在考慮布倫索 25 年與 26 年的收入以及那條曲線是什麼樣子。

Okay, that's helpful. If I could sneak a quick one for ARIKAYCE. I know you said you've already reached target enrollment of 400 patients. Can you give any color on how many patients are left in that six to eight week screening period? Thanks again.

好的，這很有幫助。如果我可以為 ARIKAYCE 偷偷溜走。我知道您說過已經達到 400 名患者的目標招募了。您能否透露一下在這六至八週的篩檢期內還剩下多少患者？再次感謝。

So the honest answer to that is I don't know off the top of my head, but I know that it's going to supplement in addition to the 400. I'm just going to ask Martina, she may know. She probably does.

因此，誠實地回答是，我不知道，但我知道它將是 400 的補充。我要去問問瑪蒂娜，她可能知道。她可能知道。

Yeah. So we have about an additional 40 to 45 patients that are in the screening period. And as you know, it takes about six to eight weeks for the culture to come through, but I think we're highly confident that we will see that in this quarter.

是的。因此我們還有大約另外 40 至 45 名患者處於篩檢期。如您所知，文化的形成大約需要六到八週的時間，但我認為我們非常有信心將在本季度看到這一點。

And how many of those you would normally --

你通常會--

At the screen -- so normally on the screen failure from these patients, we would expect to be another 15 to 20 randomized.

在篩檢中 — — 通常在篩檢失敗的這些患者中，我們預計還會有 15 到 20 名患者被隨機分配。

Perfect. There you go.

完美的。就這樣。

Liisa Bayko, Evercore ISI.

Liisa Bayko，Evercore ISI。

This is [Seema] on for Liisa. I have two questions on ARIKAYCE. So in Japan, there seems to be no growth in revenue this quarter over last quarter. So how should we think of future growth in this territory? And my second question is, you are meeting with FDA this quarter to discuss the possibility of an accelerated approval to expand the label for ARIKAYCE in frontline.

這是 [Seema] 為 Liisa 表演的。我對 ARIKAYCE 有兩個問題。因此在日本，本季的營收似乎沒有比上一季有所成長。那我們該如何看待這一領域的未來發展呢？我的第二個問題是，您本季將與 FDA 會面，討論加速批准擴大 ARIKAYCE 在前線使用標籤的可能性。

This year, Japan did not consider ARISE data for label expansion enough because of the shorter duration of treatment. So including, like, other reason of that, it did not include Japanese patients. So where do you see the possibility that FDA might agree to accelerated approval? Those are my questions. Thank you.

今年，日本由於治療時間較短，沒有充分考慮ARISE數據進行標籤擴展。因此，包括其他原因在內，它不包括日本患者。那麼您認為 FDA 同意加速核准的可能性有多大？這些都是我的問題。謝謝。

Sure. So I'll take the second question first and then ask Sara will take the first one. With regard to the probability of getting accelerated approval, I think we've been pretty consistent over the years just saying that we think this is a long shot, but it's an appropriate long shot to take because the data was compelling. There are certainly other divisions within FDA that have found data that is in this sort of realm of clear and compelling plus the background history here of the success of the drug. It's full approval in Europe and Japan.

當然。因此，我先回答第二個問題，然後請 Sara 回答第一個問題。關於獲得加速批准的可能性，我認為我們多年來一直一致認為這是一個長遠的目標，但這是一個適當的長遠目標，因為數據令人信服。當然，FDA 內部的其他部門也發現了這種清晰、令人信服的數據，以及該藥物成功的背景歷史。它在歐洲和日本都獲得全面認可。

There's a lot of reasons to believe that what we have really should be enough. But FDA has very strict rules and each division interprets them differently. So I think we think this is probably a low probability of success, but we do think it's a prudent dialogue to have. And of course, if we manage to get it, we would be super excited. We are ready to pivot to a launch earlier than expected if the accelerated approval comes our way, so I want to be clear about that.

有很多理由讓我們相信，我們所擁有的確實足夠了。但 FDA 的規定非常嚴格，每個部門的解釋都不同。因此，我認為成功的可能性很低，但我們確實認為這是一次謹慎的對話。當然，如果我們成功得到它，我們會非常興奮。如果獲得加速批准，我們準備提前推出，所以我想明確這一點。

But we're not expecting that this is the highest probability outcome. In fact, I'd say it's low. I'd say it's less than 25%. So look, it's hard to put the odds on. You're right, Japan did say no. We didn't have any Japanese patients. That always makes it difficult for them to want to approve in an early setting. But I do think it could be indicative of the way the FDA sees it as well just in terms of the overall data set.

但我們並不認為這是機率最高的結果。事實上，我想說它很低。我認為該比例低於 25%。所以看起來，這很難確定。你說得對，日本確實說了「不」。我們沒有任何日本患者。這總是使他們很難儘早獲得批准。但我確實認為，從整體資料集來看，這也可以顯示 FDA 的看法。

And then specifically on the Japan performance for the quarter, listen, I couldn't be more pleased with the performance in Japan, $21 million this quarter. And if you think about that from a year-over-year perspective, that was over 30% growth. So was very pleased with the performance. If you look at the specific dynamics between Q2 and Q3, and we don't usually get into this level of detail, but I'm happy to share it. There was a new warehouse open in Japan with some old inventory.

然後具體到本季日本的業績，我對日本的業績非常滿意，本季的業績為 2,100 萬美元。如果從同比角度來看，成長率超過 30%。所以對演出非常滿意。如果您查看 Q2 和 Q3 之間的具體動態，我們通常不會深入到這個細節層面，但我很樂意分享它。日本開設了一家新倉庫，裡面有一些舊庫存。

We needed to work down some of that inventory in Q3. So there was some favorable inventory dynamics that we mentioned in Q2. So there is some lumpiness just in general, but the fundamentals of the Japanese business continue to hum and the continuation rate is really great there. The new patient starts are really great there and couldn't be more pleased by the team's performance.

我們需要在第三季減少部分庫存。因此，我們在第二季提到了一些有利的庫存動態。因此，總體而言存在一些不穩定因素，但日本商業的基本面繼續保持良好，並且持續率確實很高。新病人的開始真的很棒，對團隊的表現感到非常滿意。

Thank you.

謝謝。

Jeff Hung, Morgan Stanley.

摩根士丹利的 Jeff Hung。

Thanks for taking my questions. Just to clarify, can you just talk about the $150 million from Pharmakon in 4Q given the cash that you have? Is that mainly for the brenso launch? And then can you talk about your current thinking on the TPIP Phase 3 study in PH-ILD, like the endpoints? And any aspects of the Phase 2 results that influence how you've been thinking about the design? Thanks.

感謝您回答我的問題。只是為了澄清一下，考慮到你們所擁有的現金，你能否談談 Pharmakon 在第四季度獲得的 1.5 億美元資金的情況？這主要是為了 brenso 的發射嗎？那麼您能談談您目前對 PH-ILD 中 TPIP 第三階段研究的想法嗎，例如終點？第二階段的結果是否影響了您對設計的思考？謝謝。

Do you want to take the question on Pharmakon?

您想回答有關 Pharmakon 的問題嗎？

Sure. The $150 million that we will receive from Pharmakon that will be reflected in our Q4 financials. That's not reflected in the approximate $1.5 billion that we have on the balance sheet today. We don't specifically say what money is specifically earmarked for which programs, of course, we have that latitude. But as we ramp up and focus on shareholder value, brensocatib is top of that list, and we are now resourced to ensure that we are fully able to appropriately resource brensocatib.

當然。我們將從 Pharmakon 獲得的 1.5 億美元將反映在我們的第四季財務表現中。這並沒有反映在我們今天資產負債表上的約 15 億美元。我們不會具體說哪筆錢專門用於哪些項目，當然我們有這個自由。但隨著我們加強並專注於股東價值，brensocatib 已成為首要關注點，而且我們目前擁有充足的資源，以確保我們能夠充分為 brensocatib 提供適當的資源。

I'm sorry, your first question was on the design of the PH-ILD study?

抱歉，您的第一個問題是關於 PH-ILD 研究的設計嗎？

Yeah. I was just curious, any aspects of the Phase 2 results that influence how you've been thinking about the design of the Phase 3 study and the endpoints that you might be using?

是的。我只是好奇，第二階段的研究結果是否影響了您對第三階段研究設計以及可能使用的終點的思考？

Yes. So we're not disclosing where we are in the final design of that study yet. I think what I would say is if you think about the Phase 2 study, which was really a safety study and had less than 40 patients randomized three toone treatment to placebo, and we still saw some very compelling directional data there that suggests improvement on time to clinical worsening, improvement in 6-minute walk, like there were some remarkable findings for what are essentially a handful of patients and the ability of the patients to go up in dose as high as they did. All of these things are very positive. So I think that sets us up for a lot of enthusiasm for Phase 3, but the specifics of the study, we haven't refined yet.

是的。因此我們尚未透露該研究的最終設計進展。我想說的是，如果您考慮第二階段的研究，這實際上是一項安全性研究，對不到 40 名患者進行了隨機分組，將三種治療方法與安慰劑進行比較，我們仍然看到一些非常令人信服的方向性數據，表明臨床惡化的時間有所改善，6 分鐘步行時間有所改善，例如對於本質上是少數的患者來說有一些了不起的發現劑量，並且能夠盡可能增加劑量。所有這些事情都是非常積極的。所以我認為這讓我們對第三階段充滿熱情，但研究的具體細節我們尚未完善。

Great. Thank you.

偉大的。謝謝。

Leon Wang, Barclays.

巴克萊銀行的 Leon Wang。

Hi, thanks for taking my question. I guess one on CEDAR. So as you kick off this study, you mentioned earlier about using 10-milligram and 40-milligram dose and the endpoint at 16 weeks. That's all pretty standard for HS studies. But I just want to clarify, what are you guys thinking in terms of the primary endpoint? Should we expect a high score of 75 as many of the new studies are kind of in HS are kind of heading in that direction for the primary endpoint?

你好，謝謝你回答我的問題。我猜 CEDAR 上有一個。因此，當您開始這項研究時，您之前提到使用 10 毫克和 40 毫克的劑量，終點是 16 週。這對於高中研究來說都是相當標準的。但我只是想澄清一下，你們對主要終點有什麼想法？我們是否應該期望 75 的高分，因為許多新的研究都處於 HS 階段，並且正朝著主要終點的方向發展？

And also a second question on ARIKAYCE. So you reiterated guidance. And right now, I would say the consensus is around the high end of that. I have 357. Can you give any pushes and pulls on what might shift your numbers for '24 to be either in the top end of the guidance or maybe on the low end? Thanks.

還有關於 ARIKAYCE 的第二個問題。所以你重申了指引。而現在，我想說大家的共識是圍繞著這個數字的高端。我有 357。您能否給予一些推動和影響，說明什麼因素可能會使 24 年的數字處於指導的最高端或最低端？謝謝。

Sure. So on the CEDAR study, I want to make it really clear. This study is an exploratory study to get a proof of concept on the mechanism in this very difficult-to-treat disease setting. So we are not looking for a statistically significant result with the design of the Phase 2 study. Instead, what we're looking for is directional information that there is a benefit through this mechanism of action in this disease state.

當然。因此，關於 CEDAR 研究，我想講清楚。這項研究是一項探索性研究，旨在對這種極難治療的疾病的機制進行概念驗證。因此，我們並不期望第二階段研究的設計能獲得具有統計意義的結果。相反，我們正在尋找的是方向性訊息，即透過這種作用機制在這種疾病狀態下可以帶來益處。

That is a very important point, because as we know, to get a statistically significant study would require many more patients, you'd have to take conservative assumptions about everything, and we really don't have the data to inform that design right now.

這是非常重要的一點，因為我們知道，要進行具有統計意義的研究需要更多的患者，你必須對一切採取保守的假設，而我們目前確實沒有數據來指導該設計。

What we're looking to do is get that directional information. It's important to also understand that we're including this interim analysis, so once we're past about 100 patients or half of the study have reached 16 weeks, we're going to take -- we're going to have a committee take a look to see if there is real efficacy that's in evidence. And if there is, we won't learn anything more about that. We'll just continue to study.

我們希望獲得方向性的信息。還需要了解的是，我們正在進行中期分析，所以一旦我們超過大約 100 名患者或一半的研究已經達到 16 週，我們將採取 - 我們將讓一個委員會來審查是否有真正的療效證據。即使有，我們也不會了解更多相關資訊。我們將繼續學習。

But if there isn't, we're going to shut it down so that we know we're not wasting precious resources. So -- but with that, maybe, Martina, you can talk a little bit more about the specifics of the primary endpoint.

但如果沒有，我們就會關閉，這樣我們就知道我們沒有浪費寶貴的資源。所以 — — 但是，也許，馬丁娜，您可以再多談談主要終點的具體情況。

Yeah. So in that context, in the primary endpoint, we're looking for a percentage change from baseline in the abscess and nodules count. That is also pretty standard as you talked. We will also look at the secondary endpoint as the first key secondary for the high score 50 as well as for the high score 75. Both of those will be informing how we would design a Phase 3study.

是的。因此，在這種情況下，在主要終點，我們正在尋找膿腫和結節數量相對於基線的百分比變化。正如您所說，這也是非常標準的。我們也將把次要終點視為高分 50 以及高分 75 的第一個關鍵次要終點。這兩者都將指導我們如何設計第三階段的研究。

Your next question comes from the line --

你的下一個問題來自--

I'm sorry, can you just hold on because there was another question there about ARIKAYCE and the range for the year. Sara, do you want to take that?

抱歉，您能等一下嗎？薩拉，你想拿著這個嗎？

Yeah, sure. Leon, thanks for the question. So specifically on the range, we were proud to be able to reiterate our guidance of $340 million to $360 million from a range perspective. I'll just remind folks that we're in our seventh year after launch. And at the midpoint of that range, it's a 15% year-over-year growth.

是的，當然。Leon，謝謝你的提問。因此，具體到範圍上，我們很自豪能夠從範圍角度重申 3.4 億至 3.6 億美元的指導價格。我只是想提醒大家，我們成立以來已經七年了。這個範圍的中間值是年增 15%。

So still very significant growth, and we were continuingly able to put up double-digit growth across each of the regions. So I couldn't be more pleased. Obviously, I can't share the -- we're in that range, but we do now have the additional 120 reps in the field. They have been deployed and are in the field as of October 1, and we feel confident to be able to reiterate the $340 million to $360 million.

因此，成長仍然非常顯著，而且我們能夠在每個地區繼續實現兩位數的成長。所以我非常高興。顯然，我無法分享——我們處於這個範圍內，但我們現在確實在該領域有額外的 120 名代表。它們已經部署完畢並於10月1日投入戰鬥，我們有信心能夠重申3.4億至3.6億美元的援助金額。

Steve Willey, Stifel.

斯蒂費爾的史蒂夫威利 (Steve Willey)。

Yeah, Good morning. Thanks for taking the questions. Just with respect to the Phase 2 PAH disclosure, curious if we should be thinking about, I guess, the nature of the Phase 2 PH-ILD disclosure as kind of proxy for how that looks like from a communication perspective. And then just wondering if you can kind of talk a little bit about how you're thinking about the hierarchical importance of some of the endpoints that are materializing out of that PAH trial.

是的，早安。感謝您回答這些問題。僅就第 2 階段 PAH 揭露而言，我很好奇我們是否應該思考第 2 階段 PH-ILD 揭露的性質，將其作為從溝通角度來看其是什麼樣子的代理。然後我想知道您是否可以稍微談談您如何看待 PAH 試驗中實現的一些終點的層次重要性。

I would imagine, given the mechanism that PVR reduction is of interest, but it's also a small study, 6-minute walk distance could be noisy. And I guess there still doesn't appear to be a lot of consensus around PVR reduction being a correlate for clinical outcomes. So just would be interested in your thoughts around the importance of the endpoints you're going to see as well. Thanks.

我可以想像，考慮到 PVR 減少的機制是令人感興趣的，但這也是一項小型研究，6 分鐘的步行距離可能會很吵。我認為對於 PVR 減少與臨床結果之間的相關性似乎仍然沒有達成很多共識。所以我只是對你對將要看到的端點的重要性的想法感興趣。謝謝。

Yeah. I think one of the goals of the study is to understand that the mechanism is going to make a material difference in patients. And if we think about PAH, it is not common to see spontaneous dramatic reductions in PVR. So to see that in evidence in this patient population, certainly, we have on a blinded basis, is very encouraging. And it would make -- lead us to believe that we would expect to see some significant impact when we unblind the study.

是的。我認為這項研究的目標之一是了解該機制將對患者產生實質的影響。如果我們考慮 PAH，就會發現 PVR 自發性大幅下降的情況並不常見。因此，看到我們在該患者群體中發現的證據，當然，這是在盲法基礎上進行的，這是非常令人鼓舞的。並且它將使我們相信，當我們揭開研究的神秘面紗時，我們將會見到一些重大的影響。

You're right, 6-minute walk is always noisy. But if we think about the PH-ILD study and the directional evidence we saw there, different disease, but nonetheless, it was positive. And I think for those reasons, we're encouraged. I think when we see other markers like NT-proBNP that are correlated with improvement in patients, and those have directionally gone the right way, all of this suggests a positive outcome here.

你說得對，步行 6 分鐘的地方總是很吵。但如果我們考慮 PH-ILD 研究和我們在那裡看到的定向證據，雖然是不同的疾病，但無論如何，它是積極的。我想，基於這些原因，我們感到鼓舞。我認為，當我們看到 NT-proBNP 等其他標記物與患者病情的改善相關，並且這些標記物朝著正確的方向發展時，所有這些都表明這是一個積極的結果。

But maybe, Martina, you can comment on how you're going to reflect on this.

但是，馬丁娜，也許你可以評論一下你將如何看待這一點。

Yeah. So the PVR reduction is the primary endpoint for a Phase 2 study. I think this is important to understand the hemodynamic measures is something that you do in the Phase 2 study, not necessarily something you do in Phase 3. So you do want to understand that. As well as 6-minute walk, you will look also -- we have PK that we will be looking at as well as clinical worsening and quality of life in these patient populations.

是的。因此，PVR 減少是第 2 階段研究的主要終點。我認為了解血流動力學測量是在第 2 階段研究中進行的，而不一定在第 3 階段進行，這一點很重要。所以你確實想了解這一點。除了 6 分鐘步行之外，您還將看到——我們將研究 PK 以及這些患者群體的臨床惡化和生活品質。

Andrea Newkirk, Goldman Sachs.

高盛的安德里亞紐柯克 (Andrea Newkirk)。

Hi all. This is [Toni] on for Andrea. Just one from us. Now that the expanded sales force is fully deployed, if you could just remind us what activities are underway with respect to both ARIKAYCE in the refractory NTM setting and also brensocatib ahead of the launch. Thank you.

大家好。這是安德里亞的 [Toni]。我們只有一個。現在擴大的銷售隊伍已經全面部署，您能否提醒我們一下，在推出之前，ARIKAYCE 在難治性 NTM 環境中以及 brensocatib 方面正在進行哪些活動。謝謝。

Sure. So the additional 120 folks bringing the U.S. sales force to 184 were deployed October 1. They keep -- they are out and detailing ARIKAYCE to the pulmonology community, but they are also doing disease state awareness about bronchiectasis. That sets us up to build those relationships and put us in a place for a best practice launch.

當然。因此，額外的 120 名員工於 10 月 1 日部署，美國銷售團隊由此達到 184 名。他們不斷地向肺病學界詳細介紹 ARIKAYCE，但他們也正在進行有關支氣管擴張的疾病狀態宣傳。這為我們建立這些關係奠定了基礎，並為我們提供了最佳實踐的發布條件。

The goal with this kind of a situation, particularly when you're first-in-disease, and in our case, that opportunity is very significant here. We draw on the experience that we had for ARIKAYCE, which was also a first-in-disease launch. You want to make sure that the community understands the burden of the disease and the need for treatment and that dialogue is established. And then if and when we're approved in the appropriate way, we would then shift at that time to discussing about the product. Obviously, we're not talking about that now.

在這種情況下的目標，特別是當你是第一個生病的人時，在我們的案例中，這個機會非常重要。我們借鑒了 ARIKAYCE 的經驗，該產品也是首次在疾病領域推出。你要確保社區了解疾病的負擔和治療的必要性，並且建立對話。然後，如果我們以適當的方式獲得批准，我們就會轉而討論產品。顯然，我們現在不談論這個。

But they are going to also be calling on ARIKAYCE, and that makes for a very natural conversation with the physicians offices. Many of these offices treat both patients and many of these patients have comorbidities with these two indications. So there's a logic here that is self-evident to the pulmonology community when our folks are in their offices.

但是他們也會拜訪 ARIKAYCE，這使得與醫生辦公室的對話變得非常自然。許多這樣的診所同時治療這兩種疾病，而且許多患者都患有這兩種疾病的合併症。因此，當我們的工作人員在辦公室時，這裡的邏輯對肺病學界來說是不言而喻的。

Graig Suvannavejh, Mizuho.

瑞穗的 Graig Suvannavejh。

Thanks for taking my question. I've got two, please. Just maybe three. The first one is just on your OpEx for the quarter. It was a bit higher than I think we were expecting. And just as we think about the rest of the year and perhaps next year, just how to think about trending?I know you've got trials ongoing. You just expanded the sales force. Just if you could give some general thoughts around that.

感謝您回答我的問題。請給我兩個。也許只有三個。第一個只是關於您本季的營運支出。我認為這比我們預期的要高一些。當我們思考今年剩餘時間甚至明年時，該如何看待趨勢？知道你正在進行試驗。你剛剛擴大了銷售團隊。但願您能就此給予一些整體想法。

And then second, just on the earlier-stage pipeline or efforts, I just want to know in the context of all you've got going that's more late stage, the prioritization or importance of those early stage efforts? And then if you could just remind me, I might have missed it, expectations on the readout of the ENCORE study for ARIKAYCE in the first-line setting? Thanks.

其次，關於早期階段的管道或工作，我只想知道，在你們進行的所有後期工作的背景下，這些早期階段工作的優先順序或重要性是什麼？然後，如果您能提醒我一下，我可能會錯過，對 ARIKAYCE 在一線環境中的 ENCORE 研究讀數的期望是什麼？謝謝。

Sure. So I'll go -- take those in reverse order and leave the first one to Sara. On the readout for ENCORE, that's expected in the early part of 2026. As we described, the enrollment there is going very well. We just need to get this last group of screened patients randomized and then we're off and running for the length of the trial, which, as you'll recall, is 13 months from start to finish.

當然。所以我會用相反的順序拿這些，並把第一個留給 Sara。根據 ENCORE 的讀數，預計將在 2026 年初實現。正如我們所描述的，那裡的招生進展非常順利。我們只需要對最後一組篩選過的患者進行隨機分組，然後我們就可以開始進行整個試驗了，正如你們所記得的，從開始到結束一共是 13 個月。

When we think about the earlier-stage efforts, the fourth pillar, as we like to refer to it, there's a lot going on there, but there's a lot going on at the company generally. And I know that most of the investment focus is on the mid-to late-stage portfolio. So we haven't spent time on describing that in any detail, but please do not take that for a minute to mean that things are not progressing there. Some of the preclinical data I've seen recently in certain disease states we're targeting is among the most compelling I've ever seen in my career. I'm super excited about what these various teams are bringing forward.

當我們思考早期階段的努力，也就是我們喜歡稱之為的第四支柱時，那裡發生了很多事情，但總體而言公司內部發生了很多事情。我知道大部分投資重點都集中在中後期投資組合。因此，我們沒有花時間詳細描述這一點，但請不要認為這意味著事情沒有進展。我最近看到的針對某些疾病狀態的某些臨床前數據是我職業生涯中所見過的最引人注目的數據之一。我對於這些不同的團隊所取得的成果感到非常興奮。

And again, remember, the intention here is for this portion of the company to produce between one and two INDs a year. That will begin in the next 12 months. And as that unfolds and the clinical data from that comes forward using several different approaches to really impactful medicines in very difficult-to-treat diseases, we will be very excited to share that with the investment community. And I think at that time, when its clinical data, that's when the investment community is going to pay more attention to it.

再次提醒，我們的目標是讓公司這部分的業務每年生產一到兩個 IND。這項工作將在未來 12 個月內開始。隨著這一進程的推進以及透過幾種不同方法獲得的臨床數據的出現，我們將非常高興地與投資界分享這些數據，這些臨床數據將用於治療難以治療的疾病。我認為，當其臨床數據公佈時，投資界就會更加關注它。

But there's a lot going on there, and that continues to be the answer to the question of what's next behind these first three programs. And also is a strong sign of what we believe is going to be a capability to produce novel medicines for the next decade or more at this company.

但那裡有很多事情發生，這仍然是關於這三個項目背後下一步是什麼的問題的答案。這也強烈表明我們相信該公司將有能力在未來十年或更長時間內生產新型藥物。

Sara, do you want to take the first question?

薩拉，你想回答第一個問題嗎？

Sure. Happy to take the first question. Thanks, Graig, for the questions. We remain committed to investing in what we truly believe will drive the most shareholder value. And you saw the balance sheet augmentations that we did this quarter, and that was really to kind of take the financing off the table.

當然。很高興回答第一個問題。謝謝格雷格提出的問題。我們依然致力於投資於我們真正相信能夠帶來最大股東價值的領域。大家看到了我們本季所做的資產負債表擴充，這其實是為了消除融資問題。

Our strategy on spending has remained unchanged to that point. Specifically on the various lines, SG&A, as expected, we will see an increase in comp and ben as we brought on the new sales force and investing in the appropriate launch readiness activities to ensure that we will have a world-class launch in what we believe will be a mega blockbuster product, assuming regulatory approval. So you'll continue to see that investment.

到目前為止，我們的支出策略一直沒有改變。具體來說，在各個產品線上，銷售、一般及行政開支，正如預期的那樣，我們將看到營收和利潤的增加，因為我們引入了新的銷售隊伍，並投資於適當的發布準備活動，以確保我們將擁有世界一流的發布，我們相信這將是一個超級重磅產品，假設獲得監管部門的批准。所以你會繼續看到這項投資。

On the R&D side, we'll continue to invest across the portfolio, ARIKAYCE, brenso on the life cycle management programs, and the additional indications, TPIP getting ready into Phase 3, obviously, the early-stage research. So you will continue to see investment there.

在研發方面，我們將繼續投資整個投資組合、ARIKAYCE、brenso 的生命週期管理計畫和其他適應症，TPIP 準備進入第 3 階段，顯然是早期研究。因此你將會繼續看到那裡的投資。

Also medical affairs, that's an important -- a very important area that does come through on the R&D line, and that's very important as we prepare for our launches and making sure the right education. So from an expense perspective, they're in line with our internal projections, nothing sort of different there, and we continue to make thoughtful and meaningful investments.

此外，醫療事務也是研發過程中非常重要的領域，當我們準備發布產品和確保正確的教育時，這一點非常重要。因此，從費用角度來看，它們與我們的內部預測一致，沒有什麼不同，我們會繼續進行深思熟慮且有意義的投資。

Andy Chen, Wolf Research.

安迪陳 (Andy Chen)，沃爾夫研究公司。

Hey guys, It's [Tuk] on the phone here for Andy. Can you comment on the competitive landscape in PAH and PH-ILD? Who do you see as strong competitors among the existing products and also upcoming pipeline products? Thank you.

嘿，大家好，我是 [Tuk]，找 Andy 打電話。您能評論一下 PAH 和 PH-ILD 的競爭格局嗎？您認為現有產品和即將推出的產品中誰是強勁的競爭對手？謝謝。

Sure. So if we talk about PAH and PH-ILD, PH-ILD, obviously, the only approved therapy there is prostanoid. If we think about what we stand to offer versus that once a day, 24 hours coverage, including nighttime at much higher doses than what can be achieved with what's available, it's a clear and compelling opportunity for physicians to improve patient treatment, assuming that the data and the regulatory path all validate that. We feel very good about the competitive profile in the PH-ILD setting. And I think our intention for TPIP is to be the cornerstone of therapy, the prostanoid of choice regardless of where it's deployed.

當然。因此，如果我們談論 PAH 和 PH-ILD，那麼 PH-ILD 顯然唯一獲準的治療方法是前列腺素。如果我們考慮我們能提供的服務與每天一次、24 小時的覆蓋範圍，包括夜間以比現有劑量高得多的劑量提供的服務相比，那麼對於醫生來說，這是一個改善患者治療的明顯且令人信服的機會，假設數據和監管途徑都證實了這一點。我們對 PH-ILD 環境中的競爭狀況感到非常滿意。我認為我們對 TPIP 的期望是使其成為治療的基石，無論其部署在哪裡，都是首選的前列腺素。

When we talk about PAH specifically, everyone is very familiar with sotatercept and the important role it's going to play in the treatment of these patients. We celebrate that. We think TPIP is a perfect complement to that drug. And the combination of those two, we think, could return patients to levels of normalcy in terms of PVR and other measures, potentially inviting some remodeling in the disease state. This would be, in my opinion, a breakthrough for these kinds of patients, and that's why we think our drug as the prostanoid of choice will change the treatment paradigm for patients with PAH and PH-ILD.

當我們具體談論 PAH 時，每個人都非常熟悉索他西普以及它在這些患者的治療中發揮的重要作用。我們對此表示慶祝。我們認為TPIP是該藥物的完美補充。我們認為，兩者的結合可以使患者的 PVR 和其他指標恢復到正常水平，並有可能重塑疾病狀態。在我看來，這對這類患者來說將是一個突破，這也是我們認為我們的藥物作為首選前列腺素類藥物將改變 PAH 和 PH-ILD 患者的治療模式的原因。

Got it. Thank you.

知道了。謝謝。

Competitive landscape with respect to other programs, obviously, we saw the data from two other companies that had DPP1s. I think as we review that data, a couple of takeaways for us. First of all, we know the mechanism works. This is further validation that DPP1 is a novel mechanism that is going to have an important role to play in the treatment of a broad range of neutrophil-mediated diseases. We're also particularly excited about the relative strength of our data to these other programs.

與其他專案相比的競爭格局顯然，我們看到了另外兩家擁有 DPP1 的公司的數據。我認為，當我們回顧這些數據時，我們可以得到幾點啟示。首先，我們知道該機制是有效的。這進一步證實了 DPP1 是一種新機制，將在治療多種中性粒細胞介導的疾病中發揮重要作用。我們也對我們的數據相對於這些其他程式的相對優勢感到特別興奮。

Obviously, there are many years behind us, but we welcome the competition. It raises awareness about the disease state, and it speaks to the importance that everybody sees for this mechanism in the future.

顯然，我們還需要很多年的時間，但我們歡迎競爭。它提高了人們對疾病狀態的認識，並表明每個人都看到了這種機制在未來的重要性。

Got it, got it. Thank you. Appreciate it.

知道了，知道了。謝謝。非常感謝。

And there are no further questions at this time. Thank you everyone for joining. This concludes today's call. You may now disconnect.

目前沒有其他問題。感謝大家的加入。今天的電話會議到此結束。您現在可以斷開連線。