United Therapeutics Corp (UTHR) 2024 Q4 法說會逐字稿

Good morning, and welcome to the United Therapeutics Corporation fourth quarter 2024 corporate update. My name is Cindy, and I will be your conference operator today. (Operator Instructions) Please note, this call is being recorded.

早上好，歡迎收聽聯合治療公司 2024 年第四季公司更新報告。我叫辛蒂 (Cindy)，今天我將擔任您的會議主持人。（操作員指示）請注意，此通話正在錄音。

I would now like to turn the webcast over to Dewey Steadman, Head of Investor Relations at United Therapeutics. Please go ahead.

現在，我想將網路直播交給 United Therapeutics 投資者關係主管 Dewey Steadman。請繼續。

Thank you, Cindy, and good morning. It's my pleasure to welcome you to the United Therapeutics fourth quarter 2024 corporate update webcast.

謝謝你，辛迪，早安。我很高興歡迎您收聽 United Therapeutics 2024 年第四季公司更新網路廣播。

Remarks today will include forward-looking statements representing our expectations or beliefs regarding future events. These statements involve risks and uncertainties that may cause actual results to differ materially. Our latest SEC filings, including Forms 10-K and 10-Q, contain additional information on these risks and uncertainties. We assume no obligation to update these forward-looking statements.

今天的言論將包括前瞻性陳述，代表我們對未來事件的期望或信念。這些聲明涉及風險和不確定性，可能導致實際結果大不相同。我們最新的 SEC 文件（包括 10-K 表和 10-Q 表）包含有關這些風險和不確定性的更多資訊。我們不承擔更新這些前瞻性陳述的義務。

Also today's remarks may discuss the progress and results of our clinical trials and or other developments with respect to our products. These remarks are intended solely to educate investors and are not intended to serve as the basis for medical decision making or to suggest that any products are safe and effective for any unapproved or investigational uses. Full prescribing information for the products are available on our website.

今天的演講也可能討論我們的臨床試驗的進展和結果以及我們產品的其他發展。這些評論僅用於教育投資者，並不旨在作為醫療決策的依據或暗示任何產品對於任何未經批准或研究用途都是安全有效的。我們的網站上提供該產品的完整處方資訊。

Accompany me on today's call are Dr. Martine Rothblatt, our Chairperson and Chief Executive Officer; Michael Benkowitz, our President and Chief Operating Officer; James Edgemond, our Chief Financial Officer and Treasurer; Dr. Leigh Peterson, our Executive Vice President of Product Development and Xenotransplantation; and Pat Poisson, our Executive Vice President of Technical Operations.

陪同我參加今天電話會議的有我們的董事長兼執行長 Martine Rothblatt 博士；我們的總裁兼營運長 Michael Benkowitz； James Edgemond，我們的財務長兼財務主管；我們的產品開發和異種移植執行副總裁 Leigh Peterson 博士；以及我們的技術營運執行副總裁 Pat Poisson。

I note that Michael Benkowitz and my colleague Harry Silvers will participate in a fireside chat and one-on-one meetings at the TD Cowen 45th Annual Healthcare Conference in Boston on March 3. And along with Gil Golden, our Chief Medical Officer, I will be at the UBS European Healthcare Conference on March 4 in London. And finally, James Edgemond, Harry, and I will be at the Leerink Global Healthcare Conference in Miami on March 11.

我注意到 Michael Benkowitz 和我的同事 Harry Silvers 將於 3 月 3 日參加在波士頓舉行的 TD Cowen 第 45 屆年度醫療保健會議的爐邊談話和一對一會議。我和我們的首席醫療官吉爾·戈爾登 (Gil Golden) 將於 3 月 4 日參加在倫敦舉行的瑞銀歐洲醫療保健會議。最後，James Edgemond、Harry 和我將於 3 月 11 日參加在邁阿密舉行的 Leerink 全球醫療保健會議。

Then our scientific, commercial, and medical affairs teams will present at the 20th annual John Wayne Memorial Symposium in London on March 7 and 8, and at the International Society for Heart and Lung Transplantation conference in Boston on April 27 to the 30.

然後，我們的科學、商業和醫療事務團隊將於 3 月 7 日至 8 日出席在倫敦舉行的第 20 屆年度約翰·韋恩紀念研討會，並於 4 月 27 日至 30 日出席在波士頓舉行的國際心肺移植協會會議。

And now I'll turn the webcast over to Martine for an overview of our development pipeline and business activities. Martine?

現在，我將網路廣播交給馬丁，讓她概述我們的開發流程和業務活動。馬丁內？

Thank you, Dewey, and good morning, everyone. We have slides available for reference and I encourage you to review those at your leisure. I'm not going to speak directly to the slides.

謝謝你，杜威，大家早安。我們有可供參考的幻燈片，我鼓勵您在閒暇時查看它們。我不會直接對著投影片講話。

Congratulations to the more than 1,300 Unitarians and to you, our shareholders for supporting yet another record revenue year for United Therapeutics in 2024. In fact, 2024 was our third year in a row of record setting revenue. This amazing performance was driven by our relentless drive to deliver patients with rare and underserved diseases a broad array of solutions to help them improve their lives.

恭喜 1,300 多名一神論派教徒和我們的股東，感謝你們支持聯合治療公司在 2024 年再創紀錄的收入年。事實上，2024 年是我們連續第三年創下創紀錄的收入。這一驚人業績的背後是我們不懈地努力，為罕見疾病和服務不足的疾病患者提供廣泛的解決方案，幫助他們改善生活。

Beyond our stellar commercial performance, we have now begun our three-year cascade of clinical and regulatory events, starting with the recent IND clearance for our UKidney clinical trial. This trial is the first FDA-cleared registration supporting clinical trial of a xeno-organ and could provide an opportunity to put an end to dialysis for the hundreds of thousands of patients with end stage renal disease who cannot qualify for a human kidney transplant or who have little chance of obtaining one before their health declines. We expect the first transplant in the middle of this year.

除了我們出色的商業表現之外，我們現在已經開始了為期三年的一系列臨床和監管活動，首先是最近獲得英國腎臟臨床試驗的 IND 批准。這項試驗是首個獲得FDA批准的異種器官註冊支持臨床試驗，可以為數十萬無法獲得人體腎臟移植資格或在健康狀況惡化之前幾乎沒有機會獲得腎臟移植的終末期腎病患者提供終止透析的機會。我們預計第一次移植將在今年年中完成。

Last month, we completed enrollment of the inhaled treprostinil TETON 1 study in idiopathic pulmonary fibrosis. We expect top-line data from the TETON 2 study in the second half of this year and TETON 1 top-line data in the first half of 2026.

上個月，我們完成了特發性肺纖維化吸入曲前列尼 TETON 1 研究的患者招募。我們預計 TETON 2 研究的頂線數據將在今年下半年獲得，TETON 1 研究的頂線數據將在今年上半年獲得。

Treprostinil, which has been scientifically demonstrated to be anti-fibrotic, anti-proliferative, and anti-inflammatory is far more than just a vasodilator. We believe its multifactorial mechanisms of action could be complementary to existing approved IPF agents and even to many of the potential IPF drugs in late stage development.

曲前列尼爾已被科學證明具有抗纖維化、抗增生和抗發炎作用，遠不止於一種血管擴張劑。我們相信，其多因子作用機制可補充目前已核准的 IPF 藥物，甚至補充許多處於後期開發階段的潛在 IPF 藥物。

IPF is extremely hard to treat, but we are encouraged with the success we saw in a post hoc analysis of IPF patients with pulmonary hypertension in the INCREASE study. Our goal is to bring this potential innovation to market as quickly as possible to patients in need of something additional to existing therapies on the market.

IPF 極難治療，但在 INCREASE 研究中對患有肺動脈高壓的 IPF 患者的事後分析中看到的成功令我們感到鼓舞。我們的目標是盡快將這項潛在的創新推向市場，幫助那些需要市場上現有療法之外的其他療法的患者。

And that's not all. We're tremendously excited for the potential of ralinepag to be the first true once a day oral prostacyclin antagonist for pulmonary arterial hypertension patients. If successful, ralinepag could fundamentally change the positioning of prostacyclins in the PAH treatment paradigm, potentially leading to the upfront use of prostacyclins in PAH.

但這還不是全部。我們非常高興 ralinepag 有可能成為第一個真正意義上的每天一次口服的治療肺動脈高壓患者的前列環素拮抗劑。如果成功的話，ralinepag 可能會從根本上改變前列環素在 PAH 治療模式中的定位，這有可能導致前列環素在 PAH 中的優先使用。

As an example of the potential for ralinepag, selexipag, a twice daily oral prostate antagonist, logs more than $1.5 billion in annual US sales, and this is for a twice daily oral product with a dose ceiling. Unlike ralinepag we expect to conclude enrollment in the ADVANCE outcome study later this year, allowing for top line data in 2026.

以 ralinepag 的潛力為例，selexipag 是一種每日口服兩次的前列腺拮抗劑，在美國每年的銷售額超過 15 億美元，而且這還是一種每日口服兩次且有劑量上限的產品。與 ralinepag 不同，我們預計將在今年稍後完成 ADVANCE 結果研究的招募，以便在 2026 年獲得頂線數據。

Literature has long suggested that earlier prostacyclin use leads to better results, and a once a day oral would complement traditional ERA and PDE 5 orals that PAH patients generally use for first line therapy. Any one of these potential products, UKidney inhaled treprostinil for IPF or ralinepag could fundamentally change how patients with ESRD, IPF, or PAH respectively are treated. And each represents a multibillion dollar revenue opportunity for us.

長期以來，文獻一直表明，早期使用前列環素可獲得更好的效果，而每日一次的口服藥物可以補充 PAH 患者通常用於一線治療的傳統 ERA 和 PDE 5 口服藥物。這些潛在產品中的任何一種，例如用於治療特發性肺纖維化的 UKidney 吸入式曲前列尼爾或 ralinepag，都可能從根本上改變 ESRD、特發性肺纖維化或肺動脈高壓患者的治療方式。每一個都為我們帶來了數十億美元的收入機會。

We've posted record revenue performance, progressed several registration studies, and launched the first revolutionary trial of a xeno-organ. We remain focused on the needs of you, our shareholders, through a disciplined financial algorithm and capital allocation philosophy.

我們取得了創紀錄的收入業績，推進了多項註冊研究，並啟動了首次異種器官的革命性試驗。透過嚴謹的財務演算法和資本配置理念，我們始終關注您（我們的股東）的需求。

In the past five quarters we have touched on all three areas of our capital allocation philosophy across both our commercial and development portfolios. We've invested in CapEx to support our new Tyvaso DPI manufacturing facility and acquired additional real estate to support future commercial manufacturing needs. We also commissioned the world's first clinical scale DPF in Virginia and planned to complete two others.

在過去的五個季度中，我們已經觸及了商業和開發投資組合中資本配置理念的所有三個領域。我們已經投資了資本支出來支持我們新的 Tyvaso DPI 製造工廠，並收購了額外的房地產來支持未來的商業製造需求。我們也在維吉尼亞州委託建造了世界上第一個臨床規模的 DPF，並計劃完成另外兩個。

On corporate development, we acquired IVIVA and Miromatrix to enhance our organ alternative development expertise, and we've licensed in new technologies to support our Treprostinil business. And with all this, we still returned $1 billion to you, our shareholders through an accelerated share repurchase program that was universally well received. We will continue to evaluate all three core areas of our capital allocation philosophy on an ongoing basis.

在企業發展方面，我們收購了 IVIVA 和 Miromatrix，以增強我們的器官替代開發專業知識，並且我們已獲得新技術許可來支援我們的曲前列尼爾業務。儘管如此，我們仍然透過普遍好評的加速股票回購計畫向我們的股東返還了 10 億美元。我們將繼續持續評估我們的資本配置理念的所有三個核心領域。

Record performance, progress with our innovative and revolutionary development programs, disciplined financial management and capital allocation. We've never been in a better position at United Therapeutics, and we're excited to forge ahead in 2025.

透過創新和革命性的發展計劃、嚴格的財務管理和資本配置，記錄業績並取得進步。在 United Therapeutics，我們從未處於如此好的地位，我們很高興能夠在 2025 年繼續前進。

And with that, I'll now turn the call over to our President, Mike Benkowitz, who will give an overview of our commercial performance for the quarter. Mike?

現在，我將電話轉給總裁 Mike Benkowitz，他將概述我們本季的商業表現。麥克風？

Thank you, Martine, and good morning everyone. Today, as Martine mentioned, we are pleased to report another year of record breaking revenue driven by double digit percent revenue growth for all our major revenue contributors Tyvaso, US Remodulin, Orenitram, and Unituxin, leading to almost 24% growth over a full year 2023.

謝謝你，馬丁娜，大家早安。今天，正如馬丁所提到的，我們很高興地報告，我們又創下了一年的收入記錄，這得益於我們所有主要收入貢獻者 Tyvaso、US Remodulin、Orenitram 和 Unituxin 的收入均實現了兩位數的百分比增長，從而使 2023 年全年的收入增長了近 24%。

For the quarter, we saw 20% revenue growth from the fourth quarter of 2023 and saw record total treprostinil referrals and patient shipments along with near record total starts. Our fourth quarter total net revenue was down slightly sequentially, while our gross revenues for the fourth quarter was record setting. The modest decline in net revenue is due in part to our recent contracting efforts for Tyvaso, which I will discuss in a moment.

本季度，我們的營收較 2023 年第四季成長了 20%，曲前列尼爾總轉診量和病患出貨量創下了歷史新高，總開機量也接近歷史新高。我們第四季的總淨收入環比略有下降，但第四季的總收入創下了歷史新高。淨收入的小幅下降部分是由於我們最近為 Tyvaso 簽訂的合同，我稍後會討論這個問題。

Total Tyvaso revenue for the fourth quarter was $416 million, a 19% increase over the previous year. This continued strong commercial execution in what is normally a seasonally challenging quarter was driven by record patient shipments and near record referrals and starts largely on par with the previous quarter.

Tyvaso 第四季總營收為 4.16 億美元，比上年成長 19%。在通常具有季節性挑戰性的季度中，商業執行力持續強勁，這得益於創紀錄的患者出貨量和接近創紀錄的轉診量，並且開局與上一季度基本持平。

The sequential decline in Tyvaso revenue from 3Q to 4Q was primarily driven by a larger gross to net deduction associated with our recent contracting efforts that we've been highlighting for the last few quarters. Our investment in these contracting efforts was conducted to help position nebulized Tyvaso and Tyvaso DPI at parity with current and potential future competitor products.

Tyvaso 收入從第三季到第四季的連續下降主要是由於我們最近幾季一直強調的最近的承包工作導致的總扣除額與淨扣除額擴大所致。我們對這些承包工作進行投資是為了幫助霧化 Tyvaso 和 Tyvaso DPI 與當前和未來潛在的競爭產品保持同等地位。

As we have previously noted, these new contracts became effective over the third and fourth quarters of 2024, and we saw this impact primarily in the fourth quarter. At this point, we believe these additional investments and rebates have largely been pulled through, creating a new base from which Tyvaso can continue to grow.

正如我們之前提到的，這些新合約將於 2024 年第三季和第四季生效，我們主要在第四季看到了這種影響。目前，我們相信這些額外的投資和回扣已基本到位，為 Tyvaso 的繼續發展奠定了新的基礎。

Moving to Orenitram, we reported 28% revenue growth in the fourth quarter of 2024 to $108 million largely in line with the third quarter of 2024, and again what is normally a seasonally weak fourth quarter for specialty pharmacy ordering.

轉向 Orenitram，我們報告 2024 年第四季度的收入增長了 28%，達到 1.08 億美元，與 2024 年第三季度基本持平，而且對於專業藥房訂購來說，這通常是一個季節性疲軟的第四季度。

In the fourth quarter, we saw record patient shipments for Orenitram, close to 50% of our Orenitram starts are now coming from Remodulin transitions, indicating to us that our educational efforts around use with intermediate high risk patients needing additional PAH treatment, along with scientific discussions about the expedite study are influencing Orenitram use.

在第四季度，我們看到 Orenitram 的患者出貨量創下了歷史新高，目前接近 50% 的 Orenitram 起始劑量來自 Remodulin 過渡期，這表明我們針對需要額外 PAH 治療的中高危患者使用 Orenitram 的教育工作以及有關加快研究的科學討論正在影響 Orenitram 的使用。

Moving to a Remodulin. We reported fourth quarter worldwide revenue of $135 million up 17% from the prior year period. US revenue grew 11%, setting another record for patient shipments. We continue to see strong referral and start trends for moduling. In January, our partner DEKA received FDA clearance for the new RemunityPRO Pump. RemunityPRO is the next generation of subcutaneous pump technology, optimized and designed for patients with PAH.

轉向 Remodulin。我們報告第四季全球營收為 1.35 億美元，比去年同期成長 17%。美國收入成長了11％，創下了患者出貨量的另一個紀錄。我們繼續看到強勁的推薦和模組化的開始趨勢。一月份，我們的合作夥伴 DEKA 的新款 RemunityPRO 幫浦獲得了 FDA 批准。RemunityPRO 是下一代皮下泵技術，針對 PAH 患者進行了最佳化和設計。

RemunityPRO builds on our unique Remunity Pump platform with features designed with input from PAH practitioners and patients to further simplify daily use. Compared to Remunity, RemunityPRO offers broader accessibility through intuitive technology and incorporates a touchscreen remote with step by step guidance, streamlined alerts, simplified patient filling, and automatic pump driven priming. We expect to launch RemunityPRO later this year.

RemunityPRO 以我們獨特的 Remunity Pump 平台為基礎，其功能設計參考了 PAH 從業者和患者的意見，以進一步簡化日常使用。與 Remunity 相比，RemunityPRO 透過直覺的技術提供更廣泛的可訪問性，並結合了觸控螢幕遙控器、逐步指導、簡化警報、簡化患者填充和自動泵驅動灌注。我們預計將於今年稍後推出 RemunityPRO。

Finally, Unituxin achieved record revenue of $68 million for the fourth quarter, up 25% from the prior year quarter. US revenue for Unituxin was $62 million driven by both price and volume increases. This growth demonstrates the product's strong market presence and the effectiveness of our commercial strategies.

最終，Unituxin第四季實現了創紀錄的6,800萬美元的收入，比去年同期成長了25％。受價格和銷售上漲的推動，Unituxin 美國業務收入達到 6,200 萬美元。這一成長證明了該產品強大的市場影響力和我們商業策略的有效性。

To wrap up, we are extremely proud of our team's accomplishments this quarter as the underlying dynamics of our business remain very strong. And with the recent investment in our commercial contracting efforts, we believe we are well positioned to continue providing our important medicines to patients while delivering value to our shareholders.

總而言之，我們對團隊本季的成就感到非常自豪，因為我們業務的潛在動力仍然非常強勁。透過最近對商業承包工作的投資，我們相信我們有能力繼續向患者提供重要藥物，同時為股東創造價值。

Martine, I'll turn things back to you to run the Q&A.

馬丁娜，我將把問題交還給你，由你來進行問答。

Thank you very much, Mike. Operator, please open the lines to any questions.

非常感謝，麥克。接線員，如有任何問題請隨時與我們聯繫。

(Operator Instructions) Roger Song, Jefferies.

(操作員指示) 羅傑‧宋 (Roger Song)，傑富瑞 (Jefferies)。

Great. Congrats for the quarter. Maybe start with the top line commercial franchise given you don't provide a 2025 sales guidance, so we understand the growth trajectory for the year. And then also you mentioned some seasonality [for Q]. And then how should we think about this year in the upcoming quarters? And then I have you on two pipeline questions.

偉大的。恭喜本季。鑑於您沒有提供 2025 年的銷售指導，也許可以從頂級商業特許經營開始，這樣我們就能了解今年的成長軌跡。然後你也提到了一些季節性[針對 Q]。那麼，我們該如何看待今年接下來幾季的表現呢？然後我想問您兩個管道問題。

Thank you, Roger, for the kudos, and I'll bounce that question to Mike.

謝謝羅傑的讚揚，我會把這個問題轉交給麥克。

Sure. So I think as you kind of think about 2025 and beyond as it relates to our -- what we call our foundational business, which is our existing commercial portfolio of products. I think we've been saying for the last few quarters -- last couple of years, really, is that we expect to continue to grow double digits out into the mid-decade and then obviously, with expected ralinepag and IPF approval for Tyvaso, we can -- that growth reduction should inflect in a meaningful way.

當然。所以我認為當你想到 2025 年及以後時，它與我們所謂的基礎業務有關，也就是我們現有的商業產品組合。我想我們在過去幾個季度，也就是過去幾年裡一直在說，我們預計到本世紀中葉將繼續保持兩位數的增長，然後顯然，隨著預計的 ralinepag 和 Tyvaso 的 IPF 批准，我們可以 — — 這種增長減緩應該會以有意義的方式發生。

So really, even with the contracting efforts, we employed over the last couple of quarters, or that went to effect over the last couple of quarters. We really see no change in that perspective in terms of the base business for the next two years. So we can continue to execute commercially. And like I said, deliver that double-digit revenue growth performance.

所以實際上，即使我們在過去幾季中做出了簽約努力，或者說在過去幾季中這些努力才得以生效。從未來兩年的基礎業務角度來看，我們確實看不到這種改變。因此我們可以繼續進行商業執行。正如我所說的，實現兩位數的收入成長。

Perfect answer, Michael. Thank you.

完美的答案，麥可。謝謝。

Jessica Fye, JPMorgan.

摩根大通的傑西卡·菲伊 (Jessica Fye)。

Great. So with the first transplant for the UKidney clinical trial expected midyear, can you talk about what you'll be looking for to support proceeding to the next transplant? I think there's a waiting period in between the first and the second. And then just talk about what proof points in that program would on at larger scale investment in additional DPF facilities?

偉大的。英國腎臟臨床試驗預計在今年年中進行首例移植手術，您能談談為支持下例移植手術您將採取哪些措施嗎？我認為第一次和第二次之間有一段等待期。然後您能談談該計劃中的哪些證明點會支持對額外 DPF 設施進行更大規模的投資嗎？

Thanks, Jessica. Nice to hear your voice this morning, and I'll flip that question over to Dr. Peterson, our EVP, xeno.

謝謝，傑西卡。很高興今天早上聽到您的聲音，我將把這個問題轉交給我們的執行副總裁 xeno Peterson 博士。

Yeah. So as you mentioned, we have -- this is a single phase list study, and it starts with a cohort of six participants. And then we have a 12-week review period where we will be involving.

是的。正如您所說，這是一項單階段清單研究，從六名參與者開始。然後我們會有一個為期 12 週的審查期。

Well, we're actually involving our DSMB, which is our independent data safety monitoring committee as well as our steering committee throughout the study because it's open label, but we'll have a formal review of all of the data, safety data and as well as patient and graft survival data at that point and determine the risk-benefit ratio of going forward into the remainder of the what we have a plan of up to 50 patients.

嗯，我們實際上在整個研究過程中都讓 DSMB（獨立數據安全監測委員會）和指導委員會參與，因為它是開放標籤的，但我們將對所有數據、安全數據以及患者和移植物存活率數據進行正式審查，並確定繼續進行剩餘研究的風險收益比，我們計劃最多有 50 名患者參與。

And as far as the endpoints or the demonstration of success, we're going to be looking again at a six-month graft survival rate, patient survival rate as well as several parameters of kidney function and then, of course, of safety, which includes transmission of infections, including potential zeonatic infections.

至於終點或成功的證明，我們將再次關註六個月的移植物存活率、患者存活率以及腎功能的幾個參數，當然還有安全性，其中包括感染的傳播，包括潛在的禽流感感染。

Leigh, that's a great answer. And just in terms of additional spending on DPS facilities, it's premature to speculate on that, but it will just be something that we'll consider as the trial proceeds.

Leigh，你的回答非常好。就 DPS 設施的額外支出而言，現在推測還為時過早，但我們會隨著試驗的進行而考慮這一點。

Ash Verma, UBS.

瑞銀的 Ash Verma。

I wanted to understand how you view the Hyperion impact from WINREVAIR to your business. This study finished earlier than expected. And in the past, I understand that you've talked about that the WINREVAIR late line and combo therapy used with some of your products was kind of insulating your PAH position, but now that Windover moves earlier line and faster than expected, can Tyvaso still grow on the PAH side?

我想了解您如何看待 WINREVAIR 的 Hyperion 對您的業務的影響。這項研究比預期提前完成。而且在過去，我知道您曾談到過 WINREVAIR 後期線和與您的某些產品一起使用的聯合療法在某種程度上保護了您的 PAH 地位，但現在 Windover 的移動速度比預期的要早，Tyvaso 是否仍能在 PAH 方面實現增長？

Thank you, Ash, for dialling in this morning. Mike, I think that would be the best person to answer that question.

謝謝你，Ash，今天早上撥了電話。麥克，我認為他是回答這個問題的最佳人選。

Sure. So I think in terms of the Hyperion study, I mean, obviously, we'll see how that plays out over the next couple of quarters. As I said in the answer to the first question, we still expect that we're going to continue to grow double digits across our franchise. I do not think -- as we said all along, WINREVAIR is not a -- it's not a cure. It's definitely in addition to the PAH treatment armamentarium.

當然。因此我認為就 Hyperion 的研究而言，顯然我們將看到其在接下來的幾季中如何發展。正如我在回答第一個問題時所說的那樣，我們仍然預計我們的特許經營權將繼續保持兩位數的成長。我不認為 — — 正如我們一直所說的那樣，WINREVAIR 不是一種治癒方法。它絕對是 PAH 治療藥物的補充。

Which is great for patients. It doesn't replace prostacyclin. I think what we've seen until now is that's being eased in combination with prostacyclin. I think that will continue to be the case if for whatever reason physicians start to move use WINREVAIR ahead of prostacyclin over the long term, I think that's immaterial because PAH continues to be a progressive disease and whether patients start on prostacyclin before or after WINREVAIR eventually, they're going to get to a prostacyclin.

這對於患者來說非常好。它不能代替前列環素。我認為到目前為止我們看到的情況是，透過與前列環素聯合使用，這種症狀得到了緩解。我認為，如果出於某種原因，醫生開始長期使用 WINREVAIR 而不是前列環素，情況將繼續如此，我認為這並不重要，因為 PAH 仍然是一種進行性疾病，無論患者是在 WINREVAIR 之前還是之後開始使用前列環素，他們最終都會使用前列環素。

So as we kind of think about our business over the long term, we think the impact is going to be really be immaterial.

因此，當我們從長遠角度考慮我們的業務時，我們認為影響實際上並不大。

Excellent, Michael.

太棒了，麥可。

Joseph Thome, TD Cowen.

約瑟夫·托米（Joseph Thome），TD Cowen 公司。

Congrats on the progress. Maybe another on the xenotransplant. Can you put into context the baseline disease severity of the first patients that will be enrolled maybe as it relates to kind of the baseline disease severity of Towana Looney.

祝賀你取得進展。或許還有關於異種移植的另一個。您能否說明一下將要入選的第一批患者的潛在疾病嚴重程度，也許這與 Towana Looney 的潛在疾病嚴重程度有關。

And then related to that, we've obviously been able to follow these patients progress through either press releases from the hospitals themselves or new sources. I guess, do you expect this to continue in the formal clinical study as early as yesterday, it seems like Ms. Looney was able to return home, and we can kind of watch this as it happens. Is that going to be the case in the formal study as well?

與此相關，我們顯然能夠透過醫院本身的新聞稿或新消息來源來追蹤這些患者的進展。我想，您是否預計這將在正式的臨床研究中繼續進行，早在昨天，似乎 Looney 女士已經能夠回家了，我們可以觀察此事的進展。在正式的研究中也會這樣嗎？

Thank you, Joe. I think Dr. Peterson could give you a very good answer on that question.

謝謝你，喬。我認為彼得森博士可以對這個問題給出很好的答案。

Yeah. So I think your second question was about how we will follow our clinical study patients with regard to the news and what's been shown with Ms. Looney. We will not be doing that. Our -- for clinical studies, the data are -- there's patient privacy that we will -- it will not be the same as what you've seen with this EIND case. It will be more like a traditional clinical study where you don't have names to follow that.

是的。所以我認為你的第二個問題是關於我們將如何追蹤我們的臨床研究患者，了解相關新聞以及 Looney 女士的病情發展。我們不會這麼做。對於臨床研究，我們的數據是——我們會保護患者的隱私——它不會與您在該 EIND 案例中看到的數據相同。它將更像是一項傳統的臨床研究，沒有名字可以參考。

As far as the eligibility, it will -- our eligibility includes two populations of patients. One of our patients who are not eligible for the current kidney transplant wait list. But they don't have several comorbidities, like they're not very, very sick patients, probably like you're asking specifically about the first two heart patients. patients won't have severe cardiovascular comorbidities as well as several other.

就資格而言，我們的資格包括兩類患者。我們的一名患者不符合目前腎臟移植等候名單的資格。但是他們沒有幾種合併症，就像他們不是病情非常嚴重的患者一樣，可能就像您具體詢問的前兩位心臟病患者一樣。患者不會患有嚴重的心血管合併症以及其他一些疾病。

But again, they won't be eligible for the list due to medical reasons. And then we also have a second population, which probably Ms. Looney would fall into, which is that they are not expected to get an allo transplant do to things such as HLA sensitization or other factors, type O blood or a combination of these factors are not expected to get an allo transplant for at least five years.

但同樣，由於醫療原因，他們將沒有資格進入名單。然後我們還有第二類人群，Looney 女士可能就屬於這一類，由於 HLA 致敏或其他因素，他們預計不會接受同種異體移植，O 型血或這些因素的結合預計至少五年內不會接受同種異體移植。

And so this is a second population where, again, they're on the list, but they're not expected to really -- to have a good chance of receiving an allo transplant. So I hope that gives you a little bit of an indication, again, in comparison to Ms. Looney, where you've really been able to follow her status, which is really great.

因此，這是第二類人群，他們雖然在名單上，但預計實際上不太可能有很好的機會接受異體移植。因此，我希望這能給你一點提示，與 Looney 女士相比，你確實能夠關注她的狀態，這真的很棒。

We're really, really happy to help patients like her. And probably the second category is very similar to -- of patients is very similar to where -- what you understand and what we understand where she is.

我們真的非常高興能夠幫助像她這樣的病人。第二類可能與患者的情況非常相似，您所了解的和我們所了解的她的情況非常相似。

Thank you, Dr. Peterson. Superb 360-degree answer.

謝謝你，彼得森醫師。出色的 360 度答案。

Roanna Ruiz, Leerink.

Roanna Ruiz，Leerink。

So question about Tyvaso in PH-ILD specifically. Could prescribing growth on the ILD side plus increase in commercial volumes under Part D redesign possibly outweigh some seasonality trends from 1Q going to 2Q? Just curious if there's any color on that?

所以問題具體是關於 PH-ILD 中的 Tyvaso 的。ILD 方面的處方成長加上 D 部分重新設計下的商業用藥量增加是否可能超過從第一季到第二季的一些季節性趨勢？只是好奇那上面有顏色嗎？

Very interesting question, Roanna. Michael, can you answer that?

非常有趣的問題，羅安娜。邁克爾，你能回答這個問題嗎？

Sure. I think in terms of the first part of the question around PH-ILD growth, as you recall, we expanded our sales force coming into 2024 really to try and drive prescribing growth in the PH-ILD or -- in the ILD treaters. Those physicians that are seeing the PH-ILD patients.

當然。我認為，就 PH-ILD 成長的問題的第一部分而言，正如您所記得的那樣，我們在 2024 年擴大了銷售隊伍，實際上是為了嘗試推動 PH-ILD 或 ILD 治療者的處方成長。那些正在看 PH-ILD 患者的醫生。

So prior to that, or at least at launch and up until that, I think what we were seeing is the vast majority of PH-ILD patients were being referred to pulmonary hypertension clinics and it was those physicians that were prescribing Tyvaso. And so -- but as you kind of think of the patient population, that really wasn't a sustainable model going forward if we really were going to have an impact and to be able to penetrate the market.

因此在此之前，或至少在推出時以及在此之前，我認為我們看到的是絕大多數 PH-ILD 患者被轉診到肺動脈高壓診所，並且是這些醫生開了 Tyvaso 的處方。所以 — — 但是當你想到患者群體時，如果我們真的要產生影響並且能夠打入市場，那真的不是一個可持續的模式。

So that was really sort of the idea behind the expansion was to really start to continue to educate the ILD treaters on not only the disease but how to use Tyvaso, how to start to manage these patients. So I will say that so far has paid off in spades.

所以，擴展背後的想法實際上是開始繼續教育 ILD 治療者，不僅要教育他們有關疾病的知識，還要教育他們如何使用 Tyvaso，如何開始管理這些患者。所以我想說，到目前為止，我們已經獲得了豐厚的回報。

If you look at our prescriber growth over the course of 2024, the majority of that growth is in the ILD treating community. So we're starting to get the breadth of prescribers and in that group and then actually starting to get -- make some inroads on the depth.

如果您觀察我們 2024 年的處方成長情況，您會發現大部分成長來自於 ILD 治療族群。因此，我們開始了解開處方人員的廣度和該群體，然後實際上開始在深度上取得一些進展。

I talk often about the three-plus factors that get to three-plus patients, then they quickly jump up to 6, 7, 8, 9, 10 patients. So we're having a lot of success both in terms of the growth of -- the breadth of the prescribers and starting to get more depth among those prescribers.

我經常談論三個以上因素，這些因素會讓患者達到三個以上，然後他們很快就會達到 6、7、8、9、10 個患者。因此，我們在擴大處方人員的廣度和深入處方人員的深度方面都取得了巨大成功。

And so I think we just expect that to continue as we move on to 2025 and beyond. And I was just looking at calculating, if you look at patient growth between PH-ILD and PAH, the nice thing is with Tyvaso is we're actually growing in both indications. So in 2024, we grew roughly, I think it was about 37%, 35% to 40%. And in PH-ILD, still mid-teen growth in PAH. So it's nice to see that we're growing in both indications.

所以我認為我們預計這種情況將會持續到 2025 年及以後。我只是在計算，如果你看看 PH-ILD 和 PAH 之間的患者增長情況，Tyvaso 的優點在於我們在這兩種適應症上實際上都在增長。所以到 2024 年，我們的成長率大概是 37%、35% 到 40% 左右。在 PH-ILD 中，PAH 仍處於中青少年時期的成長。因此，我們很高興看到我們在兩個領域都取得了成長。

So I think hopefully, that addresses the first part of your question around prescriber growth and growth in PHL versus PAH. As it relates to Part D impact, I think, as we said for the last couple of quarters, I think that largely played out last year.

因此，我希望這可以回答您問題的第一部分，即有關處方人員的增長以及 PHL 與 PAH 的增長。至於它與 D 部分的影響有關，我認為，正如我們在過去幾個季度所說的那樣，我認為這在很大程度上在去年就已經顯現出來。

As we saw in Q1, we saw more PAP patients or patient assistance patients convert over to commercial paying patients in Q1 of 2024, and then that continued over the course of the year. We kind of set a bit about roughly 90% of our patients are commercial pain patients and then 10% are in our roughly 10% are in our PAP program.

正如我們在第一季看到的那樣，我們看到 2024 年第一季更多的 PAP 患者或患者援助患者轉變為商業付費患者，並且這種情況持續了一整年。在我們的病人中，大約 90% 是商業疼痛患者，另外 10% 在我們的 PAP 計劃中。

I would expect that's going to be kind of the new normal or new baseline going forward. Could shift bounce around a little bit quarter-to-quarter just depending on the type of patients we're getting in. But generally, I would expect to kind of settle in around that. So I'm not expecting to see much of an impact in Q1 or Q2 as a result of the Part D redesign.

我希望這將成為未來的新常態或新基線。根據我們接收的患者類型，每季的情況可能會有小幅波動。但一般來說，我希望能適應這種情況。因此，我預計 D 部分重新設計不會對第一季或第二季產生太大影響。

Excellent. Michael, your encyclopedic knowledge is the benefit to all of us. Thank you so much. Really appreciate it. Operator, we only have time for one last question.

出色的。邁克爾，你的廣博知識使我們所有人都受益。太感謝了。真的很感激。接線員，我們只剩下時間回答最後一個問題了。

And whoever that may be, maybe there'll be a question for our Chief Financial Officer since this is an earnings call.

無論是誰，也許都會向我們的財務長提出一個問題，因為這是一個收益電話會議。

Andreas Argyrides.

安德烈亞斯·阿吉里德斯。

Thanks for taking our question. And Martine, apologies, you put me on the spot on the financial question. I don't think I had that one teed up here. But first of all, kudos to the great year and also to the milestone on getting IND clearance and you're leading the way and it's pretty fascinating and interesting going forward here. And following to one of progress here hearing this resume daily activities and kudos to the team.

感謝您回答我們的問題。馬丁，抱歉，你在財務問題上讓我很為難。我認為我還沒有在這裡準備好這個。但首先，我要對這偉大的一年以及獲得 IND 批准的里程碑表示祝賀，你們引領了潮流，未來的發展相當令人著迷和有趣。接下來是聽到這裡的一項進展，恢復日常活動並向團隊致敬。

My question was really just quickly around Tyvaso in IPF getting a sense of the intellectual property moat that you've built around that, how long you can expect exclusivity? And then quickly on contracting and some of the competitive dynamics behind that. I don't know if I squeeze too in there, but apologies for that.

我的問題實際上只是想快速了解一下 Tyvaso 在 IPF 中建立的知識產權護城河，您可以期待多長時間的獨家經營權？然後快速討論合約及其背後的一些競爭動態。我不知道我是否擠在那裡，對此我深表歉意。

Yeah. Okay. Well, thank you, Andreas. We appreciate your kudos; you're off the hook on the question for James. We don't really like to discuss publicly the issues relating to IPF (inaudible)

是的。好的。好吧，謝謝你，安德烈亞斯。我們感謝您的讚揚；你對詹姆斯的問題沒有回答。我們不太喜歡公開討論與 IPF 相關的問題（聽不清楚）

And we're about out of time, so I'm going to ask just Michael if he could talk about the contracting aspects of our anticipated launch into IPF. Michael?

我們的時間快到了，所以我想問邁克爾他是否可以談談我們預計進軍 IPF 的承包方面的問題。麥可？

Yeah. So Andreas, I'm not sure if it was -- the question was related directly to contracting and IPF or just contracting generally or what we've done thus far. But really, I think the philosophy that we -- and the strategy we employed last year was to start to lock in payers with some additional rebates in anticipation of future competitors.

是的。所以安德烈亞斯，我不確定是否 - 這個問題是否與承包和 IPF 直接相關，或者只是一般的承包，或者我們迄今為止所做的工作。但實際上，我認為我們的理念——以及我們去年採用的策略是開始透過一些額外的回饋來鎖定付款人，以應對未來的競爭對手。

And then, the idea behind that is if we start to have those rebate dollars flowing through, then regardless of where the potential competitor comes in with rebates, we have dollars flowing through. And so that puts us, I think -- we think, in a stronger position.

然後，背後的想法是，如果我們開始有那些回扣資金流入，那麼無論潛在競爭對手從哪裡獲得回扣，我們都會有大量資金流入。所以我認為，這會讓我們處於更有利的地位。

It keeps us at parity. I think payers will be less reluctant -- or less likely, more reluctant to enter into contracts that would disadvantage us because at that point, they basically be turning off the spigot of the rebate dollars.

它使我們保持平等。我認為付款人將不會那麼不情願——或者說不太可能，更不願意簽訂對我們不利的合同，因為到那時，他們基本上就關閉了退款的閥門。

So that was really the idea behind the payer strategy, which is get the rebates in place, start to get those dollars flowing keep us at parity with competitors. And then we feel like if we're really -- and then have the discussion with the clinicians around what's the better product for their patients, and we feel very strongly that we're better positioned and very well positioned to succeed on that front.

所以這實際上是付款人策略背後的想法，即獲得回扣，開始讓這些資金流動起來，並讓我們與競爭對手保持平價。然後我們覺得，如果我們真的——然後與臨床醫生討論什麼是對他們的患者更好的產品，我們就會非常強烈地感覺到，我們在這方面處於更有利的位置，並且很有可能取得成功。

Thank you, Mike. Perfect answer. Operator, you may now wrap up the call.

謝謝你，麥克。完美的答案。接線員，您現在可以結束通話了。

Thank you for participating in today's United Therapeutics Corporation earnings webcast. A rebroadcast of this webcast will be available for replay for one-week by visiting the Events & Presentation section of the United Therapeutics Investor Relations website at ir.unither.com. You may now disconnect. Thank you.

感謝您參加今天的聯合治療公司收益網路廣播。您可透過造訪 United Therapeutics 投資者關係網站 ir.unither.com 上的「活動與演示」部分來重播該網路廣播，重播時間為一週。您現在可以斷開連線。謝謝。