United Therapeutics Corp (UTHR) 2021 Q4 法說會逐字稿

Good morning, and welcome to the United Therapeutics Corporation Fourth Quarter and Full Year 2021 Earnings Webcast. My name is Emma, and I will be your conference operator today. (Operator Instructions)

早安，歡迎收看聯合治療公司 2021 年第四季和全年收益網路廣播。我叫艾瑪，今天我將擔任你們的會議操作員。 （操作員說明）

I will now turn the webcast over to Dewey Steadman, Head of Investor Relations at United Therapeutics.

我現在將網路廣播交給 United Therapeutics 投資者關係主管 Dewey Steadman。

Good morning, and thank you, Emma. It's my pleasure to welcome you to the United Therapeutics Corporation Fourth Quarter and Full Year 2021 Earnings Webcast. Accompanying 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; Pat Poisson, our Executive Vice President of Technical Operations; and Dr. Leigh Peterson, Senior Vice President of Product Development.

早安，謝謝你，艾瑪。我很高興歡迎您觀看 United Therapeutics Corporation 2021 年第四季和全年收益網路廣播。陪同我參加今天的電話會議的是我們的董事長兼執行長 Martine Rothblatt 博士； Michael Benkowitz，我們的總裁兼營運長； James Edgemond，我們的財務長兼財務主管； Pat Poisson，我們的技術營運執行副總裁； Leigh Peterson 博士，產品開發資深副總裁。

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.

今天的言論將包括代表我們對未來事件的期望或信念的前瞻性陳述。這些陳述涉及風險和不確定性，可能導致實際結果有重大差異。我們最新的 SEC 文件（包括表格 10-K 和 10-Q）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。

Today's remarks may also include financial measures that were not prepared in accordance with U.S. generally accounted -- generally accepted accounting principles. A reconciliations of these non-GAAP financial measures to the most directly comparable GAAP financial measures can be found in our earnings release available on our website at ir.unither.com.

今天的言論可能還包括未按照美國公認會計原則制定的財務措施。這些非 GAAP 財務指標與最直接可比較的 GAAP 財務指標的調整表可以在我們網站 ir.unither.com 上發布的收益報告中找到。

Today's remarks may discuss the progress and results of clinical trials 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 these products are available on our website.

今天的發言可能會討論我們產品的臨床試驗或其他進展的進展和結果。這些言論僅旨在教育投資者，無意作為醫療決策的基礎，或表明任何產品對於任何未經批准或研究用途都是安全有效的。這些產品的完整處方資訊可在我們的網站上找到。

Now I'll turn the call over to Dr. Rothblatt for an overview of the fourth quarter and full year 2021 financial results and business activities of United Therapeutics. Dr. Rothblatt?

現在我將把電話轉給 Rothblatt 博士，以了解 United Therapeutics 第四季和 2021 年全年財務表現和業務活動的概述。羅斯布拉特博士？

Good morning, and thank you, Dewey, for that great introduction. We are very excited about this 2021 annual results call. It's -- 2021, I think, beyond the doubt, has been the most exciting year in our company's history. There are a couple of big picture observations here that I'd like to start with, and then I'll go into some more details.

早安，謝謝杜威的精彩介紹。我們對這次 2021 年度業績電話會議感到非常興奮。我認為，2021 年毫無疑問是我們公司歷史上最令人興奮的一年。我想從一些大的觀察開始，然後我將討論更多細節。

From the big picture standpoint, first of all, we grew both patient count and revenues by double-digit percentages in 2021, as we had forecast we would do at the start of the year. Generics have not impacted our treprostinil growth trajectory because patients, physicians, payers, they all recognize our outstanding commitment and track record for customer service and supply chain reliability. Our continued double-digit percentage patient growth is how we get to our announced goal of 25,000 patients by 2025, and we remain right on target to make that goal. In fact, we expect double-digit patient growth again this year in 2022.

從大局來看，首先，我們在 2021 年的患者數量和收入都實現了兩位數百分比的成長，正如我們在年初所預測的那樣。仿製藥並沒有影響我們的曲前列環素的成長軌跡，因為患者、醫生、付款人都認可我們在客戶服務和供應鏈可靠性方面的傑出承諾和記錄。我們持續兩位數百分比的患者成長是我們實現宣布的到 2025 年患者數量達到 25,000 名的目標的原因，而且我們仍然朝著實現這一目標的目標前進。事實上，我們預計 2022 年患者數將再次達到兩位數成長。

The second grow big picture item is that our organ manufacturing products made a dramatic and highly successful debut with 1 (inaudible) UHeart, 2 (inaudible) UKidneys and 2 UThymoKidneys transplanted. Of course, the focus of everybody is on our living UHeart recipient, Mr. David Bennett Sr. So I'm very pleased to report that he is doing well at almost 2 months post transplant. Specifically, his cardiovascular function at 7 weeks is excellent, and there's no sign of rejection even after a 30-day postoperative biopsy. Although he has a lot of non-heart serious health challenges, he said last night, "Thank you for this chance to live." And my response to Mr. Bennett was, "Thank you, Mr. Bennett for giving us this chance to let countless thousands of others also live."

第二個發展大計畫是我們的器官製造產品首次亮相，取得了戲劇性的成功，移植了 1 個（聽不清楚）UHeart、2 個（聽不清楚）UKidneys 和 2 個 UThymoKidneys。當然，每個人的焦點都集中在我們活著的 UHeart 接受者 David Bennett Sr. 先生身上。所以我很高興地向大家報告，他在移植後近 2 個月時狀況良好。具體來說，他在第7週時的心血管功能非常好，即使在術後30天的活檢後也沒有出現排斥反應的跡象。儘管他面臨著許多非心臟方面的嚴重健康挑戰，但他昨晚表示，“感謝你給我這個活下去的機會。”我對貝內特先生的回應是：“貝內特先生，謝謝你給我們這個機會，讓無數其他人也能活下去。”

I believe our clear cut successes in 2021 with xeno products coupled with our core competencies in this area, our GalSafe meat, for example, was approved by the FDA in December 2020, and our core competencies in GMP manufacturing and product development, all show that our organ manufacturing pipeline is now more credible than ever and of truly momentous potential.

我相信，我們在2021 年在異種產品方面取得的明顯成功，加上我們在該領域的核心能力，例如，我們的GalSafe 肉類於2020 年12 月獲得FDA 批准，以及我們在GMP 製造和產品開發方面的核心能力，都顯示：我們的器官製造管道現在比以往任何時候都更加可靠，並且具有真正巨大的潛力。

Now beyond these big picture headlines, there has been a great deal of progress in advancing our pharmaceutical pipeline as well. Some highlights are: first, our once-daily treatment for PAH, ralinepag, is progressing nicely toward wrapping up its Phase III enrollment. Second, our Phase III PERFECT trial, which is testing a first-ever treatment for COPD-related pulmonary hypertension is steadily racking up more patient randomizations month-by-month toward completion of its Phase III trial. Our revolutionary disease-modifying effort of idiopathic pulmonary fibrosis, or IPF, which we call the TETON trial is doing so well in its U.S. Phase III enrollment that we opened up a TETON 2 Phase III trial outside the U.S. so that we could hopefully offer this product worldwide.

現在，除了這些大頭條新聞之外，我們在推進製藥管道方面也取得了很大進展。一些亮點是：首先，我們每日一次的 PAH 治療藥物 ralinepag 正在順利完成 III 期註冊。其次，我們的 III 期 PERFECT 試驗正在測試首個治療慢性阻塞性肺病相關肺動脈高壓的療法，該試驗正在逐月穩步增加更多的患者隨機分組，以期完成其 III 期試驗。我們針對特發性肺纖維化（IPF）的革命性疾病緩解努力（我們稱之為TETON 試驗）在美國III 期註冊中表現非常出色，因此我們在美國境外開展了TETON 2 III 期試驗，以便我們可望提供此服務產品遍佈全球。

Our super convenient Tyvaso DPI product remains well positioned for its summer 2022 launch. The FDA did just delay its approval decision from this month to May, but that 3-month detour is not important compared to the product's blockbuster revenue potential and patent life well into the 2030s. 3 months delay to start on a billion-dollar revenue trajectory is no big deal.

我們超方便的 Tyvaso DPI 產品在 2022 年夏季推出時仍處於有利位置。 FDA 只是將其批准決定從本月推遲到了 5 月，但與該產品巨大的收入潛力和長達 2030 年代的專利壽命相比，這 3 個月的繞道並不重要。延遲 3 個月開始實現 10 億美元的營收軌跡並不算什麼大事。

Mike will now brief you on our commercial progress. But in summary, for 2021, I can say we hit our patient growth and revenue growth targets. We validated 3 new veno-organ product candidates. And in so doing, we've launched a whole new category of biotechnology. We have 7 Phase III trials underway with multiple new product candidates. And most important of all, in this past year, I'd like to say we saved the life of Mr. Bennett with a (inaudible) xenoheart. We saved the life -- the live, sorry, we saved the lives of at least 100 children stricken with neuroblastoma, thanks to our Unituxin medicine.

Mike現在向您​​介紹我們的商業進展。但總而言之，對於 2021 年，我可以說我們實現了患者成長和收入成長目標。我們驗證了 3 種新的靜脈器官候選產品。透過這樣做，我們推出了一個全新的生物技術類別。我們正在進行 7 項 III 期試驗，涉及多種新候選產品。最重要的是，在過去的一年裡，我想說我們用（聽不清楚）異種之心拯救了貝內特先生的生命。我們拯救了生命——抱歉，我們拯救了至少 100 名患有神經母細胞瘤的兒童的生命，這要歸功於我們的 Unituxin 藥物。

We have now saved over 200 lives of lung transplant patients by increasing the usable donor lung supply with our lung bioengineering technology. And we have saved or improved the lives of thousands of pulmonary hypertension patients in the past year with our Remodulin, Remunity, Tyvaso and Orenitram products. From the headline saving of one life to the kind of like prayers granted saving of 100 children's lives to the now almost routine saving and improving of thousands of lives, I can most confidently report that UT's first year as a public benefit company has been super true to our public benefit purpose.

透過利用我們的肺生物工程技術增加可用的供體肺供應，我們現已挽救了 200 多名肺移植患者的生命。去年，我們透過 Remodulin、Remunity、Tyvaso 和 Orenitram 產品挽救或改善了數千名肺動脈高壓患者的生命。從拯救一個生命的頭條新聞，到拯救100 名兒童生命的祈禱，再到現在幾乎例行公事地拯救和改善數千條生命，我可以非常自信地報告，UT 作為一家公益公司的第一年是非常真實的為了我們的公共利益目的。

Mike, can you lead us off now with commercial operations?

麥克，你現在可以帶領我們開始商業營運嗎？

Sure. Thanks, Martine, and good morning, everybody. As Martine said, we're very pleased to have posted double-digit revenue and patient growth for the full year of 2021, ending the year with more than 10,000 patients on one of our treprostinil therapies. This quarter, I'd like to dive into the underlying performance of our 3 treprostinil products, Tyvaso, Remodulin and Orenitram.

當然。謝謝，馬丁娜，大家早安。正如 Martine 所說，我們很高興在 2021 年全年實現兩位數的收入和患者增長，到年底已有超過 10,000 名患者接受我們的一種曲前列環素療法。本季度，我想深入探討我們的 3 種曲前列環素產品（Tyvaso、Remodulin 和 Orenitram）的基本性能。

As usual, I'm going to focus more on our patient metrics, and I'll remind everyone that our quarterly treprostinil revenue does not always track exactly with quarterly underlying patient demand due to our specialty pharmacy partner ordering patterns. So I'll begin with Tyvaso. As you may recall, in early 2021, we established a goal to double the number of patients on Tyvaso from approximately 3,000 when the PH-ILD indication was added to the label to 6,000 by the end of 2022. This assumes no COVID-related impacts to physician access and patient initiation of therapy and importantly recognizes that our path to doubling may not be linear.

像往常一樣，我將更多地關注我們的患者指標，並且我會提醒大家，由於我們的專業藥房合作夥伴訂購模式，我們的季度曲前列環素收入並不總是與季度潛在患者需求完全一致。我將從泰瓦索開始。您可能還記得，在2021 年初，我們制定了一個目標，即到2022 年底，將Tyvaso 的患者數量從PH-ILD 適應症添加到標籤中時的約3,000 名患者增加一倍至6,000 名。這假設沒有與新冠病毒相關的影響重要的是，我們認識到我們的倍增之路可能不是線性的。

The fourth quarter was our third quarter of the PH-ILD launch. And in this quarter, we had the highest number of Tyvaso referrals, which is what we call prescriptions since launch, and we added close to 300 patients to our Tyvaso active patient census. Our new patient starts were less than Q3, which is common in the fourth quarter as many patients opt to wait until after the holidays to begin advanced therapies. Our specialty pharmacy partners are working to clear this backlog and get these patients started on therapy during the current quarter. We continue to anticipate a CMS coverage decision regarding Medicare reimbursement for Tyvaso and PH-ILD any time between now and May of this year.

第四季是我們推出 PH-ILD 的第三季。在本季度，我們的 Tyvaso 轉診數量達到了最高數量，這就是自推出以來我們所說的處方，並且我們在 Tyvaso 活躍患者普查中添加了近 300 名患者。我們的新患者開始數量少於第三季度，這在第四季度很常見，因為許多患者選擇等到假期結束後才開始高級治療。我們的專業藥局合作夥伴正在努力清理積壓的訂單，並讓這些患者在本季開始接受治療。我們繼續預計從現在到今年 5 月之間的任何時間，CMS 都會就 Tyvaso 和 PH-ILD 的醫療保險報銷做出承保決定。

All the necessary steps have been completed, including the close of a public comment period last year. We can't predict the timing of this coverage decision, but in the meantime, federal health care patients still have the opportunity to apply to our patient assistance program to access Tyvaso therapy prior to the coverage decision if they are eligible.

所有必要的步驟均已完成，包括去年公眾意見徵詢期的結束。我們無法預測此承保決定的時間，但與此同時，聯邦醫療保健患者如果符合條件，仍然有機會申請我們的患者援助計劃，以便在承保決定之前獲得 Tyvaso 治療。

We anticipate 3 core drivers for continued Tyvaso work over the next several quarters. I think I mentioned these on the last call. First, we think the CMS coverage decision in PH-ILD will be a driver for Tyvaso growth through the middle of this year. Even though federal health care patients may apply for our patient assistance program, we are hearing through the channel that many physicians are simply waiting for CMS coverage before prescribing Tyvaso in their PH-ILD patients.

我們預計未來幾季 Tyvaso 持續工作的 3 個核心驅動因素。我想我在上次通話中提到了這些。首先，我們認為 PH-ILD 的 CMS 核保決定將成為今年年中 Tyvaso 成長的驅動力。儘管聯邦醫療保健患者可能會申請我們的患者援助計劃，但我們透過管道得知，許多醫生只是在等待 CMS 承保，然後才給 PH-ILD 患者開出 Tyvaso 處方。

Second, we continue to grow the Tyvaso prescriber base, particularly among ILD treaters, and expect to see continued growth in prescriptions from these physicians over the next 2 quarters and beyond as we continue our outreach and educational efforts in this space. Up until now, the vast majority of Tyvaso prescribing has come from historical PAH trial. So there is a lot of as yet untapped potential in this area.

其次，我們將繼續擴大 Tyvaso 處方者群體，特別是 ILD 治療者，並預計隨著我們繼續在這一領域的推廣和教育工作，這些醫生的處方量將在未來兩個季度及以後持續增長。到目前為止，泰瓦索的絕大多數處方都來自歷史上的 PAH 試驗。因此，該領域還有很多尚未開發的潛力。

And finally, we view the upcoming Tyvaso DPI approval as an additional catalyst to Tyvaso growth. While we would have been thrilled with an FDA approval for Tyvaso DPI this week, as we said on our Q3 call, we've been assuming a launch by summer of this year. So nothing's really changed in that regard. In the meantime, we are completing our launch preparations, and we will be ready to launch immediately upon approval.

最後，我們將即將到來的 Tyvaso DPI 批准視為 Tyvaso 成長的額外催化劑。雖然我們對本週 FDA 批准 Tyvaso DPI 感到興奮，但正如我們在第三季電話會議上所說，我們一直假設在今年夏天推出。所以在這方面沒有什麼真正改變。同時，我們正在完成啟動準備工作，一旦獲得批准，我們將立即啟動。

Moving to Orenitram. We saw yet another quarter of record patient accounts during the fourth quarter. As we've discussed before, we believe this uptick is driven by the FREEDOM-EV label expansion now that we're able to have more robust interactions with prescribers about the data. And finally, we're pleased with the continued strong performance of Remodulin despite the launch of a generic form of subcutaneous treprostinil last year. That generic launch has continued to play out closely with what we saw with the IV generic launch in 2019, with an initial bolus of patients, primarily those dual-eligible Medicare Medicaid patients transitioning to the generic treprostinil trickling down to an immaterial number of generic transitions in recent months.

搬到奧雷尼特蘭。我們在第四季度看到了又一個季度創紀錄的患者帳戶。正如我們之前討論的，我們相信這種上升是由 FREEDOM-EV 標籤擴展推動的，因為我們能夠與處方者就數據進行更強有力的互動。最後，儘管去年推出了皮下注射曲前列環素仿製藥，但我們對瑞莫杜林持續強勁的表現感到滿意。該仿製藥的上市繼續與我們在2019 年IV 仿製藥上市時看到的情況密切相關，最初一批患者，主要是那些符合雙重資格的Medicare Medicaid 患者過渡到仿製藥曲前列環素，逐漸減少了仿製藥轉換的數量。最近幾個月。

The feedback we've received on our Remunity pump has been quite positive in our early launch efforts. As part of that feedback, we learned that the pump's alarms, can, in some cases, be overly sensitive. To be clear, the issues we're seeing with the alarms are not safety issues. But to ensure that physicians and patients have an awesome experience with the pump, we recently paused the introduction of new patients Remunity, while we work with our partner, DEKA, to optimize the alarm profile. We just completed final testing of the new alarm system. Everything is working as expected, and we will recommence our Remunity rollout next week.

在我們早期的發布工作中，我們收到的有關 Remunity 泵的回饋非常積極。作為回饋的一部分，我們了解到泵浦的警報在某些情況下可能過於敏感。需要明確的是，我們看到的警報問題並不是安全問題。但為了確保醫生和患者獲得良好的幫浦體驗，我們最近暫停了向患者推出新的 Remunity，同時與我們的合作夥伴 DEKA 合作優化警報設定檔。我們剛剛完成了新警報系統的最終測試。一切都按預期進行，我們將在下週重新開始推出 Remunity。

To wrap up, we're pleased with the progress with Tyvaso in PH-ILD. We look forward to a CMS coverage decision in May or earlier. Likewise, we're on track to achieve our 6,000 patients on Tyvaso by the end of the year, and we're pleased with the continued momentum for Orenitram.

總而言之，我們對 Tyvaso 在 PH-ILD 方面取得的進展感到滿意。我們期待在 5 月或更早做出 CMS 承保範圍決定。同樣，我們有望在今年年底前讓 Tyvaso 患者達到 6,000 名，我們對 Orenitram 的持續成長勢頭感到高興。

Finally, we think that our Remodulin revenues will remain robust despite generic competition, especially once we recommence the introduction of new patients to the Remunity pump.

最後，我們認為，儘管存在仿製藥競爭，我們的 Remodulin 收入仍將保持強勁，特別是當我們重新開始將新患者引入 Remunity 泵後。

And with that, I'll turn the call back over to Martine.

然後，我會將電話轉回給 Martine。

Thanks so much, Mike. Super exciting about the Remunity breakout next week. Awesome.

非常感謝，麥克。下週的 Remunity 突破非常令人興奮。驚人的。

So operator, I understand that you probably have some people in queue and feel free to bring them on.

接線員，我知道您可能有一些人在排隊，請隨時讓他們加入。

(Operator Instructions)

（操作員說明）

Your first question today comes from the line of Joseph Thome with Cowen and Co.

你們今天的第一個問題來自約瑟夫‧托姆 (Joseph Thome) 與考恩公司 (Cowen and Co.) 的對話。

Maybe just on the Tyvaso DPI request by the FDA. Are you able to provide a little bit more information as to the type of information that you submitted? And then in terms of the safety profile you've seen with Tyvaso DPI to date, some high-level thoughts there, especially as it relates to potential for bronchospasm?

也許只是應 FDA 對 Tyvaso DPI 的要求。您能否提供更多有關您提交的資訊類型的資訊？然後，就您迄今為止看到的 Tyvaso DPI 的安全性而言，有一些高層想法，特別是與支氣管痙攣的可能性有關？

Yes. We've really had some absolutely great experience with the Tyvaso DPI to date, and we have not experienced those bronchospasm side effects that you referred to. So we really don't believe that that's going to be an issue at all. The -- there is some more information in the press release if you look down towards the second-or-so page of the press release. There should be a little bit more information there about the submission and what was admitted and not submitted. So I think it's all really quite routine and the FDA doing their job as best that they can.

是的。到目前為止，我們確實在 Tyvaso DPI 方面獲得了一些非常好的經驗，並且我們還沒有經歷過您提到的那些支氣管痙攣副作用。所以我們真的不相信這會成為一個問題。如果您向下看新聞稿的第二頁左右，那麼新聞稿中會有更多資訊。那裡應該有更多關於提交以及已接受和未提交內容的資訊。所以我認為這一切都是很平常的事情，FDA 正在盡其所能地做好他們的工作。

As I mentioned in my introductory remarks and as Mike emphasized in his remarks, 3 months is really meaningless in the context of this product's life. This product has a very long patent life. It is an amazing product. I mean it's so convenient and easy for the patients to use. We have the great results of the BREEZE trial. It's going to end up being used, I'm confident, by thousands and thousands. And over the course of its life, like, 10,000 more or more patients. It's just an amazing product. So it will get out there. Everybody just has to make sure that, like all the boxes are checked and the Is are dotted and the Ts are crossed. And as Mike said, we feel confident with the launch by the time frames that we've previously guided everyone to.

正如我在介紹性發言中提到的以及麥克在發言中所強調的那樣，對於該產品的生命週期而言，3 個月確實毫無意義。該產品具有很長的專利壽命。這是一個了不起的產品。我的意思是它對患者來說使用起來非常方便和容易。我們獲得了 BREEZE 試驗的出色結果。我相信，它最終會被成千上萬的人使用。在其生命週期中，約有 10,000 名以上的患者。這真是一個了不起的產品。所以它會出去。每個人都必須確保這一點，就像所有的方框都被選中，Is 被點綴，T 被交叉。正如麥克所說，我們對按照我們之前指導大家的時間框架進行發布充滿信心。

Your next question today comes from the line of Eun Yang with Jefferies.

今天你們的下一個問題來自 Eun Yang 和 Jefferies 的對話。

Another question on DPI. Once it's approved, does it need to go through a CMS approval process similar to the PH-ILD indication for Medicare coverage?

另一個關於DPI的問題。一旦獲得批准，是否需要經歷類似於 Medicare 承保的 PH-ILD 適應症的 CMS 審批流程？

Thank you, Eun. So nice to hear your voice this morning. I think we have a lot of experts on our call, but I think Mike Benkowitz would be the best person to respond to your question. Mike, if that's okay?

謝謝你，恩。很高興今天早上聽到你的聲音。我認為我們的電話會議中有很多專家，但我認為邁克·本科維茨（Mike Benkowitz）是回答你的問題的最佳人選。麥克，這樣可以嗎？

Sure. Happy to take that question. So there is a seamless approval process that will need to happen or review process that will need to happen with Tyvaso DPI, but it's different than what we're experiencing with PH-ILD. So for PHI -- sorry, for PH-ILD. So right now, PH-ILD is approved for use with our TD-300 nebulizer, and it's covered in the medical benefit or Part B side -- B as a boy side of Medicare. The DPI will be a pharmacy benefit product, so covered in Part D. So the process is a little different.

當然。很高興回答這個問題。因此，Tyvaso DPI 需要一個無縫的審批流程或審查流程，但這與我們在 PH-ILD 上遇到的情況不同。所以對於 PHI——抱歉，對於 PH-ILD。因此，目前 PH-ILD 已獲批准與我們的 TD-300 霧化器一起使用，並且它包含在醫療福利或 B 部分（B 部分作為 Medicare 的男孩部分）中。 DPI 將是一種藥品福利產品，因此包含在 D 部分中。因此過程略有不同。

So while Medicare is reviewing the data, reviewing the product for coverage, patients can still access -- federal health care patients can still access DPI. The physician simply has to go through an appeal process, and they're accustomed to doing this. They have to do this often with products that aren't on Medicare formulary, and it's just an extra step they have to go through it and then it gets approved. So we won't see this -- we won't see the same issue we're seeing with PH-ILD where we have this hold up with the DPI. Those will continue to go through with doctors, like I said, doing this additional step of a dealing.

因此，雖然 Medicare 正在審查數據、審查產品的承保範圍，但患者仍然可以存取——聯邦醫療保健患者仍然可以存取 DPI。醫生只需要經過上訴程序，他們已經習慣這麼做了。他們必須經常對不在醫療保險處方中的產品進行此操作，這只是他們必須執行的額外步驟，然後才能獲得批准。所以我們不會看到這一點——我們不會看到我們在 PH-ILD 中看到的相同問題，而我們在 DPI 中遇到了這種情況。正如我所說，這些將繼續與醫生進行，以進行額外的處理步驟。

Your next question today comes from the line of Jessica Fye with JPMorgan.

今天您的下一個問題來自摩根大通的 Jessica Fye。

Curious what proportion of Tyvaso patients are currently on free drug -- and what are the next clinical or manufacturing milestones we should look out for in the organ transplant business? And what results in your mind would justify ungating the potential investment in the first GMP or GMP-like manufacturing facilities for those products?

好奇目前接受免費藥物的泰瓦索患者比例是多少，以及我們在器官移植業務中應該關注的下一個臨床或生產里程碑是什麼？您認為什麼結果可以證明取消對這些產品的第一個 GMP 或類 GMP 生產設施的潛在投資是合理的？

Great, Jess. So happy to hear you on the call. We think of you as one of the KOLs of pharmaceutical analyst. So it's always exciting to hear your voice here. I think the first part of your question is probably best answered by Mike. And then, Mike, if you bounce it back over to me, I'll then talk about the xeno aspects of Jess' question.

太棒了，傑西。很高興聽到你打電話。我們認為您是藥物分析師的 KOL 之一。所以在這裡聽到你的聲音總是令人興奮。我認為麥克可能最好地回答了你問題的第一部分。然後，麥克，如果你把它回饋給我，我會談談傑西問題的異種方面。

Sure. This question has come up, I think, a couple of times over the last year. So as a baseline, -- there's always a small percentage, I would say, kind of low to mid-single-digit percentage of patients that are in our patient assistance program at any point in time. What's the -- we need to wait for the CMS coverage decision on PH-ILD, that has continued to increase. And so I think on the last call, I had reported that it was getting up into kind of the higher single digits about to cross over into double digits. We've now crossed over into double digits. So it's in -- it's double-digit percentage of patients, but it's on the low end of double-digit percentage. Martine?

當然。我想，這個問題在去年已經出現好幾次了。因此，作為基線，我想說，在任何時間點，參與我們患者援助計劃的患者總有一小部分處於低至中個位數的比例。這是什麼——我們需要等待 CMS 對 PH-ILD 的覆蓋範圍決定，該覆蓋範圍持續增加。所以我認為在最後一次通話中，我報告說它正在上升到更高的個位數，即將跨越兩位數。我們現在已經突破兩位數了。因此，患者的比例為兩位數，但處於兩位數百分比的低端。馬丁娜？

Perfect. Yes. That's great, Mike. Jess, it's really interesting, the launch of these new xeno products. And we have in our call, in fact, Dr. Peterson. She is our Senior Vice President for Product Development, and she will be leading the effort now to take those products through their clinical development process. We also have on the call, Pat Poisson, who is our Executive VP for Technical Operations; and then people underneath him, who right now are responsible for our manufacturing on biologic called -- our biologic products such as Unituxin. They will be responsible for manufacturing this new type of biologic, the xenografts, be they the UHearts, the UKidneys or the UThymoKidneys.

完美的。是的。太棒了，麥克。傑西，這些新的異種產品的推出真的很有趣。事實上，我們的電話裡有彼得森博士。她是我們負責產品開發的高級副總裁，她現在將領導這些產品通過臨床開發過程。我們還有負責技術營運的執行副總裁 Pat Poisson 參加電話會議。然後是他下面的人，他們現在負責我們的生物製品的製造，我們的生物製品，例如Unituxin。他們將負責製造這種新型生物製品，即異種移植物，無論是 UHearts、UKidneys 還是 UThymoKidneys。

So all of that is very much moving into the clinical development phase. And it's super exciting doing the things like identifying the clinical trial centers, identifying the clinical investigators, putting together the necessary protocol having the meetings with the FDA to get buy into the protocol, the clinical development, our biostatisticians are already computing the necessary clinical trial parameters. So everybody is kind of rolling their oars in the same direction toward those clinical development and gating milestones for those products. So I think you're going to see all of that in the near term.

因此，所有這些都正在進入臨床開發階段。做一些事情是非常令人興奮的，例如確定臨床試驗中心、確定臨床研究人員、制定必要的方案、與 FDA 舉行會議以接受方案、臨床開發，我們的生物統計學家已經在計算必要的臨床試驗參數。因此，每個人都在朝著同一個方向推動這些產品的臨床開發和里程碑。所以我認為你會在短期內看到所有這些。

And in between, you may hear of certain kind of expanded access opportunities that arise, such as with the case of Mr. Bennett where there's a possibility for a leading surgeon at a leading hospital to uniquely save somebody's life through the unique advantages of these Xenografts. So I think you'll see some of that as well.

在這兩者之間，您可能會聽到某種擴大進入的機會，例如貝內特先生的案例，領先醫院的領先外科醫生有可能透過這些異種移植的獨特優勢來拯救某人的生命。所以我想你也會看到其中的一些。

In the case of Mr. Bennett, there were no other alternatives, and here he is almost 2 months out, no sign of rejection. I just could not be more proud of all of the efforts of our group at Revivicor how they were able to carefully splice in all of these different 10 genes to make that heart -- in the words of Dr. Griffith, the transplant surgeon, he keeps telling me, "Martine, this heart is a rock star." And this is the guy who's like did the second Jarvik heart. I mean, he really knows his stuff. And in the words of, for example, Dr. Montgomery at NYU. He is just so impressed with the -- it's hard to get a little bit graphic here, but like the urine produced by the xeno kidney, super, super impressed with it.

就貝內特先生而言，沒有其他選擇，他已經快兩個月了，沒有任何拒絕的跡象。我對 Revivicor 團隊的所有努力感到非常自豪，他們如何能夠小心地拼接所有這 10 個不同的基因來製造心臟——用移植外科醫生格里菲斯博士的話來說，他一直告訴我，「馬丁，這顆心是一顆搖滾明星。”這就是賈維克的第二顆心臟。我的意思是，他真的很了解他的東西。例如，用紐約大學蒙哥馬利博士的話來說。他對這個印象非常深刻——很難在這裡得到一點圖形，但就像異種腎臟產生的尿液一樣，超級非常印象深刻。

Dr. Locke, the Head of transplant down at UAB, she's placed her xeno kidneys into Mr. Parson was one of the seeking donors, orthotopic positions for the kidneys. She's done another similar type of xeno kidney transplant, and in both cases, is just super, super pleased with the outcome. So this xenotransplantation train has definitely, definitely, definitely just left the station. And I think you're going to see some really exciting ungating of the clinical development and production spending, capital expansion opportunities right up ahead.

Locke 博士是 UAB 的移植主任，她將自己的異種腎臟放入 Parson 先生中，Parson 先生是尋求腎臟原位捐贈者之一。她還進行了另一種類似類型的異種腎移植，在這兩種情況下，她對結果都非常非常滿意。所以這趟異種移植列車肯定、肯定、肯定剛出站。我認為你將會看到一些非常令人興奮的臨床開發和生產支出的取消，以及未來的資本擴張機會。

Your next question comes from the line of Andreas Argyrides with Wedbush Securities.

您的下一個問題來自 Wedbush Securities 的 Andreas Argyrides。

Before I get into questions, just congrats on the quarter and all the life-saving progress that you've made. It's a true testament to your dedication to it. So we appreciate that, too. So just continuing on the xenotransplantation, could you maybe give us a little bit more color around how you think? Or what the next kind of major milestone would be in these programs? Is it 6 months out? And then looking at DPI approval, how are you looking at that launch contributing to -- or the potential launch contributing to growth of patients on Tyvaso this year and next year as well.

在我提出問題之前，先祝賀本季以及您在拯救生命方面取得的所有進展。這是您奉獻精神的真實證明。所以我們也很欣賞這一點。那麼，繼續進行異種移植，您能否給我們更多關於您的想法的資訊？或者這些計劃的下一個重大里程碑是什麼？是6個月了嗎？然後看看 DPI 的批准，您如何看待該發布對今年和明年 Tyvaso 患者成長的貢獻，或潛在的發布對 Tyvaso 患者成長的貢獻。

Thank you so much, Andreas, for the questions. And thank you for the recognition of us doing our best with our public benefit purpose. Mike, if I could call on you again to answer first the DPI-related question, and then I'll follow up with the xeno-related question?

非常感謝安德烈亞斯提出的問題。感謝您對我們為公益目的所做的努力的認可。麥克，我是否可以再次請您先回答與 DPI 相關的問題，然後再回答與異種相關的問題？

Sure. On the DPI launch, as I said in my opening remarks, we'll hear back from the FDA in May, assuming that's an approval and we're ready to go, ready to launch. We have everything in place and ready to go. We'll have inventory, plenty of inventory. We actually had our launch meeting with our sales team this week. So they're prepped and ready to go, and so we'll be able to really press play on our launch once we hear back from the FDA. And we do think that there's opportunities in both PH-ILD, as I mentioned, to accelerate growth there as well as PAH. So there's really, I think, a lot of excitement and enthusiasm around the Tyvaso DPI. And I think it really is going to create an opportunity for us to expand the number of patients that we're able to help with prostacyclin therapy and PAH as well as PH-ILD, as I said. So we look at that as being a significant contributor to our march to 25,000 patients by the end of 2025. As Martine said, it should be a blockbuster drug, that's certainly how we view it, and how we're planning to approach it from a launch perspective.

當然。關於 DPI 的推出，正如我在開場白中所說，我們將在 5 月份收到 FDA 的回复，假設這是批准，並且我們已經準備好，準備推出。我們一切就緒，準備出發。我們會有庫存，大量的庫存。實際上，我們本週與銷售團隊舉行了啟動會議。所以他們已經準備好了，準備好了，所以一旦我們收到 FDA 的回复，我們就能夠真正推動我們的發布。正如我所提到的，我們確實認為 PH-ILD 和 PAH 都有機會加速成長。因此，我認為，Tyvaso DPI 確實引起了人們的極大興奮和熱情。正如我所說，我認為這確實將為我們創造一個機會，擴大我們能夠幫助接受前列環素治療、PAH 以及 PH-ILD 的患者數量。因此，我們認為這是我們在 2025 年底前向 25,000 名患者進軍的重要貢獻者。正如 Martine 所說，它應該是一種重磅藥物，這當然是我們的看法，也是我們計劃如何從發射視角。

Thanks so much, Mike. Andreas, with regard to the next thing that you might hear about, it's I think that there is a pretty good likelihood that there will be some sort of an announcement, and again, knock on wood and cross my fingers, Mr. David Bennett Sr. continues to do well at the 90-day and the 6 months mark. And the reason I call those out is when the FDA looks at clinical transplantation milestones, they put a lot of emphasis on sort of like 2 weeks, 30 days, 60 days, 90 days and maybe 1 year.

非常感謝，麥克。安德烈亞斯，關於您可能會聽到的下一件事，我認為很有可能會發布某種公告，再次，敲木頭並祈禱，老大衛·貝內特先生. 在90 天和6 個月大關上繼續表現良好。我之所以指出這些，是因為當 FDA 考慮臨床移植里程碑時，他們非常重視 2 週、30 天、60 天、90 天，甚至可能是 1 年。

And we know this because one of our Phase III trials, for example, which relates to the over 200 lives we've saved with our Lung Bioengineering technology relates to getting clinical FDA approval for our second Lung Bioengineering technology, which is in its wrapping up its last couple of patients of its Phase III trial. And with this type of technology, which is kind of techno speak, it's called ex-vivo lung perfusion technology. The FDA wants to see that the patients who are on our Lung Bioengineering technology do as well at 2 weeks, 4 weeks, 3 months, 6 months, et cetera, as the patients who don't have the advantage of a Lung Bioengineering technology.

我們知道這一點，因為我們的一項 III 期試驗涉及我們用肺生物工程技術挽救了 200 多人的生命，該試驗涉及我們的第二項肺生物工程技術獲得 FDA 臨床批准，該技術即將結束III期試驗的最後幾位患者。這種技術，從技術角度來說，被稱為離體肺灌注技術。 FDA 希望看到使用我們的肺部生物工程技術的患者在 2 週、4 週、3 個月、6 個月等時的表現與沒有肺生物工程技術優勢的患者一樣好。

So that same kind of milestone metrics, I think, are going to apply in the xeno context. And our goal would be to show that our xenograft patients, of course, separately for kidneys and hearts, do as well at 2 weeks, 4 weeks, 3 months, 6 months and the year as would patients who are otherwise similarly matched but have allografts.

因此，我認為同類型的里程碑指標將適用於異種環境。當然，我們的目標是表明，我們的異種移植患者（分別進行腎臟和心臟移植）在2 週、4 週、3 個月、6 個月和一年時的表現與其他相似但進行同種異體移植的患者一樣好。

Now depending on the organ, the slope is pretty severe, even with something that has been done for decades, like allo heart transplants, you're looking at 80% to 90% survival at 1 year, which depending on -- if you are looking at the glass half full or half empty, it's like amazing, these lives were saved. But oh my god, can't we do better and not lose 10% to 20% of the people. And for things like lungs, for example, unfortunately, the curve is worse; for kidneys, it's better.

現在，根據器官的不同，斜率相當嚴重，即使是已經做了幾十年的事情，例如同種異體心臟移植，一年後的存活率為 80% 到 90%，這取決於——如果你是看著杯子半滿或半空，真是太神奇了，這些生命被拯救了。但天啊，我們就不能做得更好，不要失去10%到20%的人嗎？不幸的是，對於像肺這樣的東西，曲線更糟。對於腎臟來說，更好。

Another advantage with kidneys is you can always back up to have the patient on dialysis. So that's an advantage, a huge advantage for xeno is that there's pretty much consensus agreement around the experts in the fields that people who are -- who have rejected a previous kidney transplant and have a lot of reactive antibodies in their blood that those do not cross-react with xeno antigens. So a person who has already had a kidney transplant would have a much, much tougher climb to try to get another kidney transplant but would not likely have the same aggressive reaction to another allotransplant as -- I mean, to another xenotransplant as they would have had a very aggressive reaction to another allotransplant. So that's kind of a favorable patient category.

腎臟的另一個優點是您可以隨時支持患者進行透析。所以這是一個優勢，對於異種來說，一個巨大的優勢是，該領域的專家們幾乎達成了共識，即那些已經拒絕了先前的腎移植並且血液中含有大量反應性抗體的人，而那些人則沒有與異種抗原交叉反應。因此，一個已經接受過腎移植的人要嘗試進行另一次腎移植將需要付出更大的努力，但不太可能對另一次同種異體移植產生與另一次異種移植相同的攻擊性反應。對另一次同種異體移植產生與另一次異種移植相同的攻擊性反應。對另一次同種異體移植有非常強烈的反應。所以這是一個有利的患者類別。

There's also about 80% of the people who are on dialysis in the U.S. who do not even qualify to be on the kidney transplant list. So that's another huge patient population. Then there are patients who have been on dialysis for so long that they have actually pretty much run out of access ports in their body for dialysis, and that becomes increasingly problematic for those patients. So there are just many, many different opportunities to insert xenotransplantation into the transplant paradigm. And we are going to do it, and we're going to follow the same clinical milestones that you've seen. The FDA previously required such as 2 weeks, 30 days, 60 days, 90 days, et cetera, as for allotransplantation.

在美國，大約 80% 的透析患者甚至沒有資格列入腎臟移植名單。這是另一個龐大的患者群體。還有一些患者接受透析時間太長，實際上他們體內的透析通道已經耗盡，這對這些患者來說變得越來越成問題。因此，有許多許多不同的機會將異種移植納入移植範式。我們將會這樣做，並且我們將遵循您所看到的相同的臨床里程碑。 FDA先前對同種異體移植的要求為2週、30天、60天、90天等等。

While I see that we're at the half-hour market -- half-hour mark here. So thank you, Andreas, very much for your questions. Thanks, everybody.

我看到我們正處於半小時市場——這裡是半小時標記。安德烈亞斯，非常感謝你提出的問題。謝謝大家。

Operator -- or thank you, Dewey. And do you want me to turn it back to you or to the operator?

接線生——或者謝謝你，杜威。您希望我將其轉回給您還是接線生嗎？

Turn it to the operator.

將其交給操作員。

Okay. Operator, it's all yours.

好的。接線員，一切都是你的了。

Thank you for participating in today's United Therapeutics Corporation Earnings Webcast. A rebroadcast of this webcast will be available for replay for 1 week by visiting the Events and Presentations section of the United Therapeutics Investor Relations website at ir.unither.com.

感謝您參加今天的聯合治療公司收益網路廣播。透過造訪 United Therapeutics 投資者關係網站 ir.unither.com 的活動和演示部分，可以重播該網路廣播 1 週。

Thank you. You may now disconnect.

謝謝。您現在可以斷開連線。