Liquidia Corp (LQDA) 2023 Q4 法說會逐字稿

Good morning, and welcome, everyone, to the Liquidia Corporation full year 2023 financial results and corporate update conference call. My name is Michelle, and I will be your conference operator today. (Operator Instructions) I would like to remind everyone that this conference is being recorded.

早安，歡迎大家參加 Liquidia Corporation 2023 年全年財務表現及公司更新電話會議。我叫米歇爾，今天我將擔任您的會議主持人。（操作員指示）我想提醒大家，本次會議正在錄音。

I would now like to hand the conference over to Jason Adair, Chief Business Officer.

現在，我想將會議移交給首席商務官傑森·阿代爾 (Jason Adair)。

Thank you, Michelle. It's my pleasure to welcome everyone to liquidity as full year 2023 financial results and corporate update call. Joining the call today are Chief Executive Officer, Dr. Roger Jeffs; Chief Operating Officer and CFO, Michael Kaseta; Chief Commercial Officer, Scott Moomaw; Chief Medical Officer, Dr. Rajeev Saggar; and General Counsel, Rusty Schundler.

謝謝你，米歇爾。我很高興歡迎大家參加 2023 年全年財務表現和公司更新電話會議。今天參加電話會議的有執行長 Roger Jeffs 博士；營運長兼財務長 Michael Kaseta；商務長 Scott Moomaw；首席醫療官 Rajeev Saggar 博士；以及總法律顧問 Rusty Schundler。

Before we begin, please note that today's conference call will contain forward-looking statements, including those statements regarding future results, unaudited and forward-looking financial information as well as the company's future performance and or achievements. These statements are subject to known and unknown risks and uncertainties, which may cause our actual results or performance to be materially different from any future results or performance expressed or implied on this call. For additional information, including a detailed discussion of our risk factors, please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed on our website.

在我們開始之前，請注意，今天的電話會議將包含前瞻性陳述，包括有關未來結果、未經審計和前瞻性財務資訊以及公司未來業績和/或成就的陳述。這些聲明受已知和未知的風險和不確定性的影響，這可能導致我們的實際結果或表現與本次電話會議中表達或暗示的任何未來結果或表現有重大差異。如需更多信息，包括我們的風險因素的詳細討論，請參閱公司向美國證券交易委員會提交的文件，可在我們的網站上查閱。

I would now like to turn the call over to Roger for our prepared remarks, after which we'll open up the call for your questions.

現在，我想將電話轉給羅傑，讓他發表我們準備好的發言，然後我們將開始回答大家的提問。

Thank you, Jason. Good morning, everyone, and thank you for joining us today. While today's call is intended to review the company's accomplishments in the last year, we know that physicians, patients and our investors are solely focused on one thing. The potential FDA approval in the coming weeks of YUTREPIA, our novel dry powder formulation of treprostinil.

謝謝你，傑森。大家早安，感謝大家今天的參與。雖然今天的電話會議旨在回顧公司過去一年的成就，但我們知道醫生、患者和我們的投資者只專注於一件事。我們的新型曲前列尼爾乾粉製劑 YUTREPIA 可能在未來幾週內獲得 FDA 批准。

I will ask Rusty to address the legal and regulatory path to approval in more detail shortly, but to put it simply with the recent decisions by the Federal Circuit, affirming the invalidity of the sole patent that is blocking our approval. The FDA should be able to grant approval for your YUTREPIA after March 31, when regulatory exclusivity to treat PH-ILD with Tyvaso expires.

我將請 Rusty 盡快更詳細地介紹獲得批准的法律和監管途徑，但簡單地說，根據聯邦巡迴法院最近做出的裁決，確認阻礙我們獲得批准的唯一專利無效。3 月 31 日之後，當 Tyvaso 治療 PH-ILD 的監管特許經營權到期時，FDA 應該能夠批准您的 YUTREPIA。

I provide -- a precise final approval date is hard to forecast, but we view the remaining step as largely procedural. Final FDA approval has always been the goal, and we have never been closer or better prepared than today. Our commercial teams are in place and ready for launch, our expanded field force has been raising the profile of Liquidia in their best of Liquidia in their territories over the last three months.

我認為——很難預測準確的最終批准日期，但我們認為剩下的步驟基本上是程序性的。獲得 FDA 的最終批准一直是我們的目標，而我們從未像今天這樣接近目標、準備充分。我們的商業團隊已經到位並準備好啟動，我們擴大的實地力量在過去三個月中一直在提升 Liquidia 在其領土內最優秀 Liquidia 的知名度。

Our manufacturing team is preparing inventory in anticipation of eventual launch in both PAH and PH-ILD. Our R&D team continues to build clinical knowledge by studying YUTREPIA and PH-ILD patients in the open label ASCENT trial and our finance team has positioned the company with the resources and discipline required to execute a successful launch. We entered 2024 at a full sprint due to the resolve and execution of our team in 2023.

我們的製造團隊正在準備庫存，以期最終在 PAH 和 PH-ILD 推出。我們的研發團隊透過在開放標籤 ASCENT 試驗中研究 YUTREPIA 和 PH-ILD 患者來繼續累積臨床知識，我們的財務團隊為公司提供了成功發布所需的資源和紀律。由於我們團隊在 2023 年表現出的決心和執行力，我們全力衝刺進入了 2024 年。

Last year, everything grew in the right direction. Our confidence grew with legal wins. Our balance sheet grew with key transactions by Marquee investors and insiders and our pipeline grew with the in-license of L606, the most clinically advanced next generation sustained release inhaled treprostinil program. Given the proximity of a potential launch. I'd like to spend a little time framing the potential market opportunity for you directly as we see it, both in PH-ILD and PAH. With regard to PH-ILD current (technical difficulty).

去年，一切都朝著好的方向發展。隨著法律上的勝利，我們的信心增強了。隨著 Marquee 投資者和內部人士的關鍵交易，我們的資產負債表不斷增長，隨著 L606（臨床上最先進的下一代緩釋吸入曲前列尼爾計畫）的許可，我們的產品線不斷擴大。考慮到潛在發射的接近性。我想花一點時間為您直接描述我們所看到的潛在市場機會，包括 PH-ILD 和 PAH。關於 PH-ILD 電流（技術難度）。

However, these estimates likely undervalue the total addressable population. Since those calculations rely on historical publications before the field had effective tools to treat the disease and therefore reasons to diagnose the disease. With inhaled treprostinil as the only approved mechanism to treat PH-ILD, the market penetration is still in its infancy. We believe there is significant growth in this market. Total inhaled treprostinil revenues currently sit at about a $1.3 billion annual run rate in the US alone.

然而，這些估計可能低估了總可尋址人口。由於這些計算依賴於該領域出現治療該疾病的有效工具之前的歷史出版物，因此也依賴診斷該疾病的理由。由於吸入曲前列尼爾是治療 PH-ILD 的唯一核准機制，因此市場滲透仍處於起步階段。我們相信這個市場將有顯著的成長。目前，光是在美國，吸入曲前列尼爾的年總收入就約為 13 億美元。

With regard to PAH, we also believe that YUTREPIA have potential for significant uptake. We view YUTREPIA having the potential to not only be the best in class inhaled treprostinil, given its dosing flexibility and ease of use but also the first in choice process. Specifically, patients who previously considered to oral prostacyclins at their starting choice, can now avoid the significant and limiting off-target GI toxicities associated with these drugs, while still achieving therapeutic doses.

關於 PAH，我們也相信 YUTREPIA 具有顯著的吸收潛力。我們認為 YUTREPIA 不僅有潛力成為同類最佳的吸入性曲前列尼爾，因為它具有劑量靈活性和易用性，而且也是首選方法。具體來說，先前考慮口服前列環素的患者現在可以避免與這些藥物相關的顯著且限制性的脫靶胃腸道毒性，同時仍能達到治療劑量。

That's combining current sales of oral prostacyclins of approximately $1.6 billion in PAH, with the recently reported sales from inhaled treprostinil of $1.3 billion. The market opportunity for YUTREPIA could be approaching $3 billion and growing incrementally as the PH-ILD patients still remain largely untreated. With its unique and differentiated, differing or approach (technical difficulty) very attentive for YUTREPIA for the investor value in both of these markets.

這是將目前口服前列環素在 PAH 領域的銷售額約 16 億美元與最近報導的吸入性曲前列尼爾的銷售額 13 億美元相結合的結果。由於 PH-ILD 患者仍大部分未治療，YUTREPIA 的市場機會可能接近 30 億美元，並且呈現逐步成長趨勢。YUTREPIA 憑藉其獨特、差異化、差異化的方法（技術難度）非常關注這兩個市場的投資者價值。

At this time, I would like to ask Rusty to summarize the next steps towards final FDA approval.

現在，我想請 Rusty 總結一下獲得 FDA 最終批准的下一步措施。

Thank you, Roger. I'd like to group the recent litigation and regulatory activity into two buckets. First, this those items on the critical path YUTREPIA approval. Second, the recent attempts by United Therapeutics to serve new legal theories to block approval, YUTREPIA. All told, we see the increased and frantic litigation activity by United Therapeutics as perhaps a sign that even they believe that the legal impediments to final approval of YUTREPIA, we are nearing an end. In the first bucket I mentioned as we have publicly stated previously, there are only two items on the critical path for YUTREPIA to be launched.

謝謝你，羅傑。我想將最近的訴訟和監管活動分為兩類。首先，這是關鍵路徑上的那些項目YUTREPIA批准。其次，United Therapeutics公司最近試圖援引新的法律理論來阻止YUTREPIA的批准。總而言之，我們看到聯合治療公司日益增多且瘋狂的訴訟活動，這或許表明，即使他們也認為，阻礙 YUTREPIA 最終批准的法律障礙即將結束。在我提到的第一個桶子中，正如我們之前公開聲明的那樣，YUTREPIA 的啟動關鍵路徑上只有兩項。

First, as Andrew's must lift the injunction who ordered in August 2022, based on this finding of infringement and for ‘793 Patent. A Patent it has subsequently been invalidated a finding that was affirmed again yesterday when the Federal Circuit denied United Therapeutics requests for retail. And second, the regulatory exclusivity granted to Tyvaso for the PH-ILD indication must expire, which will occur on March 31. Once both of these have occurred, the FDA will have the ability to issue final approval for YUTREPIA for both the PAH and PH-ILD indication.

首先，安德魯必須解除 2022 年 8 月基於侵權認定和針對’793 專利下達的禁令。一項專利隨後被宣告無效，而昨天聯邦巡迴法院駁回了聯合治療公司的零售請求，這一裁定再次得到確認。其次，授予 Tyvaso 用於 PH-ILD 適應症的監管獨佔權必須到期，該到期日為 3 月 31 日。一旦上述兩個情況都發生，FDA 將有權對 YUTREPIA 治療 PAH 和 PH-ILD 做出最終批准。

We will not speculate on the specific date when Judge Andrews will render his decision, but the matter has been fully briefed and can be decided at any time. In the second bucket. Over the last several weeks, United Therapeutics has sought to add new impediments FDA approval in our launch of YUTREPIA by seeking preliminary injunctions and multiple proceedings.

我們不會猜測安德魯斯法官作出裁決的具體日期，但此事已經充分簡報，可以隨時作出裁決。在第二個桶子裡。在過去幾週中，United Therapeutics 公司試圖透過申請初步禁令和多項訴訟，為我們推出 YUTREPIA 獲得 FDA 批准增加新的障礙。

However, as we have stated previously, in order to obtain any preliminary injunctions, the burden will be on United Therapeutics to convince the judge that among other things they are likely to succeed on the merits and those actions. We believe that this burden will be a challenge for them to meet based on the laws and the facts that issue.

然而，正如我們之前所說，為了獲得任何初步禁令，聯合治療公司必須承擔舉證責任，以說服法官，除其他事項外，他們很可能在實質問題和這些行動上取得成功。我們相信，無論從法律或從事實出發，這項負擔對他們來說都是一個挑戰。

The first request for preliminary injunction is directed to the second Hatch-Waxman lawsuit alleging infringement of the 327 Patent in the treatment of PH-ILD issued after the YUTREPIA NDA was submitted and [after] Liquidia amended its NDA to add PH-ILDs to label for YUTREPIA. The 327 Patent covers the treatment of PH-ILD patients with Tyvaso. In accordance with the dosing regimen in the Tyvaso labels.

第一項初步禁令請求針對的是第二起 Hatch-Waxman 訴訟，該訴訟指控在 YUTREPIA NDA 提交後以及 Liquidia 修改其 NDA 以將 PH-ILD 添加到 YUTREPIA 標籤後發布的 PH-ILD 治療中侵犯了 327 專利。327 專利涵蓋使用 Tyvaso 治療 PH-ILD 患者。按照 Tyvaso 標籤中的給藥方案進行。

As we've noted previously, there's considerable prior art teaches the treatment of PH-ILD patients with five Asia, including the 73 patent and multiple peer-reviewed publications in the decade prior to the priority date from 327 Patent that describes positive results from trading PH-ILD patients with Tyvaso. [Of course] have generally refrain from issuing preliminary injunctions and situations where there are substantial questions as to the validity of a patent. And in light of all the prior at here, we believe substantial questions of validity of the 327 Patent exist.

正如我們之前所指出的，有大量現有技術教導使用泰瓦索治療 PH-ILD 患者，其中包括 73 項專利和在優先權日之前十年中的多篇同行評審出版物，這些專利描述了使用泰瓦索治療 PH-ILD 患者的積極成果。 [當然]一般不會發布初步禁令，也不會在專利有效性受到實質質疑的情況下發布。並且鑑於之前的所有情況，我們認為 327 專利的有效性存在重大問題。

Second Request for preliminary injunction is directly United Therapeutics recently filed suit against the FDA under the Administrative Procedures Act. Filed in the United States District Court for the district of Columbia to suit alleges that the FDA mistakenly permitted Liquidia to amend the NDA for your YUTREPIA to add the PH-ILD indication.

第二次初步禁令請求是 United Therapeutics 最近根據《行政程序法》對 FDA 直接提起的訴訟。向美國哥倫比亞特區地方法院提起的訴訟稱，FDA 錯誤地允許 Liquidia 修改 YUTREPIA 的 NDA，以添加 PH-ILD 適應症。

We have intervened in the case and are now a party to the case alongside the FDA. First and foremost, the FDA did, in fact, accept our amendment to the NDA for review, and we believe that the FDA's acceptance of our amendment for review was proper and in full accordance with current FDA regulations. United Therapeutics argument that an amendment to add a new indication is in proper is based primarily on a non-binding 2004 FDA guidance documents. Ignoring subsequent FDA regulations adopted in 2016 that expressly contemplate the possibility of adding new indications through an amendment.

我們已介入此案，現在與 FDA 並列成為此案的一方。首先，FDA 確實接受了我們對 NDA 的修改進行審查，我們認為 FDA 接受我們的修改進行審查是正確的，並且完全符合現行 FDA 法規。聯合治療公司認為，增加新適應症的修正案是恰當的，這一論點主要基於 2004 年不具約束力的 FDA 指導文件。忽視 2016 年通過的後續 FDA 法規，該法規明確考慮透過修訂增加新適應症的可能性。

Secondly, even if United Therapeutics was correct that the amendment was improper, that would not mean that United Therapeutics would receive a new 30-month stay as they have argued, for instance, even if the amendment was now rejected by the FDA, Liquidia could simply supplement its NDA after approval to add the PH-ILD indication. Exact same process used by United Therapeutics that PH-ILD the label for Tyvaso.

其次，即使 United Therapeutics 公司正確地認為該修正案不恰當，也不意味著 United Therapeutics 公司會像他們所主張的那樣獲得新的 30 個月的暫緩期，例如，即使該修正案現在被 FDA 拒絕，Liquidia 公司也可以在獲得批准後簡單地補充其 NDA，以添加 PH-ILD 適應症。United Therapeutics 所採用的流程與 PH-ILD 為 Tyvaso 貼上標籤的流程完全相同。

Critically, the statute expressly states that amendments and supplements the exact same way in determining whether a patent can give rise to a 30-month stay, meaning that only those patents submitted to the Orange Book prior to the filing date of the original NDA, not the filing date of the amendment or supplement can give rise to a 30-month stay. Briefing on the motion for preliminary injunction will be completed on March 18, and a hearing will be held on March 29. We look forward to this matter being addressed in short order.

至關重要的是，該法規明確規定，修訂和補充在確定專利是否能夠獲得 30 個月的暫緩期方面的方式完全相同，這意味著只有在原始保密協議的提交日期（而不是修訂或補充的提交日期）之前提交給橙皮書的專利才能獲得 30 個月的暫緩期。初步禁制令動議的簡報將於 3 月 18 日完成，聽證會將於 3 月 29 日舉行。我們期待此事能盡快解決。

In summary, Liquidia sees the path to launching the YUTREPIA and two straightforward actions. Removal of the injunction and approval of the products. The rest as a last ditch attempt by a competitor to make any and every argument they can to maintain their monopoly and deny patients access to a meaningful treatment option. We have long anticipated the possibility that United Therapeutics could engage in such a flurry of activity as we need near clearance of the original Hatch-Waxman litigation, and we are prepared to meet them head-on.

總而言之，Liquidia 看到了啟動 YUTREPIA 的途徑和兩個直接的行動。取消該產品的禁令和批准。其餘的都是競爭對手的最後一次嘗試，他們竭盡全力維持壟斷地位，並拒絕讓患者獲得有意義的治療選擇。我們早就預料到，由於我們需要接近完成最初的 Hatch-Waxman 訴訟，聯合治療公司可能會採取如此大規模的行動，我們已經做好了迎面迎接他們的準備。

With that, I will pass to Mike for a review of last year's financial.

說完這些，我將交給麥克來審查去年的財務狀況。

Thank you, Rusty, and good morning, everyone. The company has never been in a stronger financial position than it is now, heading towards its first product -- first major product launch. The financial discipline we've shown to date has not only allowed us to fully engage in defending against the litigation campaign that has been directed against us, but as demonstrated to the savvy investors that we can meet and exceed expectations as we look to build value in the company without overspending or incurring significant dilution.

謝謝你，Rusty，大家早安。該公司的財務狀況從未像現在這樣強勁，並且即將推出其首款產品——首個重大產品。我們迄今所展現的財務紀律不僅使我們能夠全力應對針對我們的訴訟活動，而且向精明的投資者證明，我們可以滿足並超越預期，因為我們希望在不超支或不發生重大稀釋的情況下為公司創造價值。

Turning to our full 2023 financial results, which can be found in the press release, you will see that revenue was $17.5 million for the year in 2023 compared with $15.9 million in 2022, tied to our promotion agreement with Sandoz to commercialize Treprostinil injections. The increase of $1.6 million was primarily due to favorable gross-to-net chargeback rebate and managed care adjustments, offset by the impact of lower sales quantities as compared to the prior year.

查看我們的 2023 年完整財務業績（可在新聞稿中找到），您會發現 2023 年全年收入為 1750 萬美元，而 2022 年為 1590 萬美元，這與我們與 Sandoz 達成的推廣協議有關，以商業化曲前列尼爾注射劑。160 萬美元的增幅主要歸因於有利的總淨退款回扣和管理式醫療調整，但與上年相比銷售數量下降的影響被抵消了。

Cost of revenue was roughly the same for 2023 and 2022 at $2.9 million. Cost of revenue relates to the promotion agreement. Research and development expenses were $43.2 million in 2023 compared with $19.4 million in 2022. The increase of $23.8 million or 122% was primarily due to the $10 million upfront license fee payment to Pharmosa for the exclusive license to develop and commercialize L606 from North America, plus an additional $2.6 million in support of that program.

2023 年和 2022 年的收入成本大致相同，為 290 萬美元。收入成本與促銷協議有關。2023 年研發費用為 4,320 萬美元，而 2022 年為 1,940 萬美元。增加 2,380 萬美元或 122%，主要由於向 Pharmosa 支付 1,000 萬美元的前期許可費，以獲得在北美開發和商業化 L606 的獨家許可，另外還支付 260 萬美元用於支持該計劃。

Expenses related to our YUTREPIA program increased to $13 million from $6.7 million the year prior, primarily due to increased manufacturing of prelaunch commercial supply and the start-up of our ASCENT study. Personnel and consulting expenses, including stock-based compensation expense, also increased $5.1 million, primarily due to increased headcount to support the potential commercialization of YUTREPIA.

與我們的 YUTREPIA 計畫相關的費用從去年的 670 萬美元增加到 1300 萬美元，這主要是由於發射前商業供應的製造增加和我們的 ASCENT 研究的啟動。包括股票薪酬費用在內的人員和諮詢費用也增加了 510 萬美元，這主要是由於增加員工人數以支持 YUTREPIA 的潛在商業化。

General and administrative expenses were $44.7 million in 2023 compared with $32.4 million in 2022. The increase of $12.3 million or 38% was primarily due to a $9.8 million increase in personnel and consulting expenses, including stock-based compensation. Partially driven by the expansion of our field force and also a $1.4 million increase in commercial expenses in preparation for the commercial, potential commercialization of YUTREPIA.

2023 年一般及行政費用為 4,470 萬美元，而 2022 年為 3,240 萬美元。增加 1,230 萬美元或 38% 主要是由於人員和諮詢費用（包括股票薪酬）增加 980 萬美元。部分原因是我們外勤人員的擴大，以及為 YUTREPIA 的商業化和潛在商業化做準備而增加 140 萬美元的商業費用。

In summary, we incurred a net loss in 2023 of $78.5 million as compared to a net loss of $41 million in 2022. We ended the year with the $83.7 million cash on hand and then quickly added another $100 million in the first week of January with a private placement of equity to a single investor and a third advance from HealthCare Royalty under our agreement from January 2023. In summary, we are well positioned to achieve our corporate objectives in 2024.

總之，我們 2023 年的淨虧損為 7,850 萬美元，而 2022 年的淨虧損為 4,100 萬美元。年底時，我們的現金餘額為 8,370 萬美元，然後在 1 月的第一周通過向單一投資者進行股權私募以及根據我們自 2023 年 1 月起達成的協議從 HealthCare Royalty 獲得第三筆預付款，迅速又增加了 1 億美元。總而言之，我們已做好準備，在 2024 年實現我們的企業目標。

I would now like to turn the call back over to Roger.

現在我想把電話轉回給羅傑。

Thank you, Mike. 2024 is shaping up to be the translation transformational year as Liquidia. We are fourth in the starting blocks in the EU and rest of both described and saw earnestly to get where we are today. We look forward to proving ourselves in the market with more importantly, easing the burden of patients suffering from these debilitating diseases.

謝謝你，麥克。 2024 年有望成為 Liquidia 翻譯轉型之年。我們在歐盟起跑線上排名第四，其他人都認真描述並看到了我們今天所取得的成就。我們期待在市場上證明自己，更重要的是減輕患有這些使人衰弱的疾病的患者的負擔。

With that, I would now like to open our call up for questions. Operator?

現在，我想開始回答大家的提問。操作員？

First question, please.

請問第一個問題。

Thank you. (Operator Instructions)

謝謝。（操作員指令）

Greg Harrison, Bank of America.

美國銀行的格雷格·哈里森。

Good morning. This is Mary Kate on for Greg. Thanks for taking our question. So as you guys prepare for your commercial transition, do you see any differences in launch strategy for PAH compared to PH-ILD? Maybe why or why not? And do you anticipate equal interest in those indications? Thanks.

早安.這是瑪麗凱特 (Mary Kate) 為格雷格 (Greg) 表演的。感謝您回答我們的問題。那麼，當你們為商業轉型做準備時，你們是否認為 PAH 的發布策略與 PH-ILD 有何不同？或許是為什麼或為什麼不呢？您是否預期人們對這些跡象會抱持相同的興趣？謝謝。

Good morning, [Mary Kate], thanks for the question. So we're fortunate to have Scott Moomaw, our Chief Commercial Officer on the phone. Scott, maybe if he would like to opine on that.

早安，[瑪麗凱特]，謝謝你的提問。因此，我們很榮幸能與我們的首席商務官 Scott Moomaw 透過電話聯繫。斯科特，也許他願意對此發表意見。

Yes. So the there's a little bit of a difference in strategy. So in PAH, as you know, there are many medications already available. So it's going to be really demonstrating why our across the cycle is the best alternative relative to the other across the cycles for a lot of reasons that we can obviously get into and we believe that we will be very successful in that space. Getting earlier use of our inhaled prostacyclin neutropenia because it is so convenient because of the titration of dose. And so in that space, we will be targeting the big centers on the physicians that use prostacyclins are ready. We'll get some new positions probably, but we'll focus on the targets that do use prostacyclins.

是的。因此，策略上存在一些差異。如您所知，對於 PAH，已經有許多藥物可用。因此，這將真正證明為什麼我們的跨週期產品相對於其他跨週期產品而言是最好的選擇，原因有很多，我們顯然可以深入探討，我們相信我們將在該領域取得巨大成功。由於劑量滴定非常方便，因此可以儘早使用我們的吸入式前列環素治療中性粒細胞減少症。因此，在這一領域，我們將針對已經準備好使用前列環素的大型醫生中心。我們可能會獲得一些新的職位，但我們將重點放在使用前列環素的目標。

In PHILD, this is a relatively untapped market. And so the strategy there is going to be much more about educating on the prevalence of PH-ILD and then getting physicians to look for it. And then getting them up to treat it. And we'll be out in the community with community pulmonologists, help educating them that this condition exists and that it's deadly. And then we'll be educating them on YUTREPIA. And if they would be willing to use YUTREPIA, that's great. We will aid them in doing that.

在費城，這是一個相對尚未開發的市場。因此，該策略將更多地側重於宣傳 PH-ILD 的流行情況，然後讓醫生尋找它。然後讓他們起來治療。我們將與社區肺病專家一起走進社區，幫助人們了解這種疾病的存在，以及它的致命性。然後我們將對他們進行有關 YUTREPIA 的教育。如果他們願意使用 YUTREPIA，那就太好了。我們將幫助他們做到這一點。

If they won't. Then, of course, we would like them to refer that patient to a [PAH or ASCENT] on where it would be or would be treated. So I think that's a brief summary of how we'll approach the two markets.

如果他們不願意的話。然後，我們當然希望他們將該患者轉診至 [PAH 或 ASCENT] 醫院，以便在那裡接受治療。所以我認為這就是我們如何對待這兩個市場的簡要總結。

Great. Thank you.

偉大的。謝謝。

And maybe I'll just add a few comments. So I think in the what I said in my opening statement indicate that. In PAH we would like to be the first choice prostacyclin. And the reason I think we can do that is because really with YUTREPIA and its ability to titrate to doses that are on order of threefold more than what was originally it's possible with Tyvaso. We've changed the therapeutic index of that molecule, and that's all enabled by our PRINT technology.

或許我只想補充一些評論。所以我認為我在開場白中所說的話已經表明了這一點。在 PAH 中我們希望成為首選前列環素。我認為我們之所以能夠做到這一點，是因為 YUTREPIA 能夠將劑量調整至比 Tyvaso 最初的劑量高出三倍左右。我們改變了該分子的治療指數，這一切都歸功於我們的 PRINT 技術。

Why that's important is now we can deliver the drug for PAH patients to the site of action through the loan and avoid the significant off-target effects, which are really hampering for the oral therapies in particular. So when you look that up Uptravi, it starts at the 200 microgram dose and it's titratable up to a ceiling of 600 micrograms, but it has a ceiling and that maintenance dose is determined by tolerability. It's indicated to delay disease progression and at risk of possible and decrease in risk of possibalization. But it's improvement on 12 -- on 6 minute walk distance is modest, only 12 meters, and I believe that was that significant. The consequence of that is net therapies, 42% of those patients have diarrhea 33% have nausea and 18% had vomiting. So significant of off-target effects.

這很重要，因為現在我們可以透過貸款將藥物運送到 PAH 患者的作用部位，並避免顯著的脫靶效應，這對口服療法尤其有阻礙作用。因此，當您查看 Uptravi 時，它從 200 微克劑量開始，可滴定至 600 微克上限，但它有一個上限，並且維持劑量由耐受性決定。它可以延緩疾病進展和降低患病風險。但它在 12 分鐘——6 分鐘步行距離上的改善很小，只有 12 米，但我認為這是非常顯著的。結果是，在淨治療中，42％的患者出現腹瀉，33％的患者出現噁心，18％的患者出現嘔吐。脫靶效應非常顯著。

And I ran Orenitram is a very similar story to use TID it's titrated to effect, its indicated delay disease progression and an improved six minute walk distance. But in the largest study of that therapy in 690 patients, 69% of those patients had diarrhea, 40% had nausea and 36% had vomiting, which clearly limits dosing. So an impact user has said lately that because it's so difficult to titrate, they are actually promoting titration via the parenteral route and then transition to oral.

我運行的 Orenitram 的情況與使用 TID 的情況非常相似，它通過滴定來達到效果，這表明可以延緩疾病進展並改善六分鐘步行距離。但在對 690 名患者進行的最大規模該療法研究中，69% 的患者出現腹瀉，40% 的患者出現噁心，36% 的患者出現嘔吐，這顯然限制了劑量。因此，一位 Impact 用戶最近表示，由於滴定非常困難，他們實際上正在提倡透過腸胃外途徑進行滴定，然後過渡到口服。

So you can see this is burdensome and onerous. What YUTREPIA will then do is mitigate completely these off-target effects to the to the GI tract and allow dose titration. So again, we're going to look at the oral prostacyclin market is a significant market where we can gain steal share and we'll do that tactically after we position ourselves as the best-in-class inhaled prostacyclin, as Scott mentioned about PAH and PH-ILD.

所以你可以看出這是很繁重、很繁重的。YUTREPIA 所做的就是完全減輕這些脫靶效應對胃腸道的影響並允許劑量滴定。因此，我們再次將目光投向口服前列環素市場，這是一個重要的市場，我們可以從中搶佔市場份額，在將自己定位為同類最佳的吸入式前列環素之後，我們會策略性地做到這一點，正如 Scott 提到的 PAH 和 PH-ILD。

Operator, next question, please.

接線員，請問下一個問題。

Julian Harrison, BTIG.

朱利安·哈里森（Julian Harrison），BTIG。

Hi, good morning. Thank you for taking my question. Just to be clear, based on some of your prepared remarks, if you are forced to seek approval in PH-ILD via supplement instead of the current arrangement. Your view, is that filing a supplement with three to seven times now in the orange book should not trigger an automatic stay? And am I understanding that correctly?

嗨，早安。感謝您回答我的問題。需要明確的是，根據您準備好的一些發言，如果您被迫透過補充而不是當前的安排來尋求 PH-ILD 的批准。您的觀點是，現在在橙皮書中提交三到七次補充資料不應該觸發自動中止嗎？我的理解正確嗎？

Yes. Thanks for the question, Julien. Good morning. I let Rusty answer that. Rusty?

是的。謝謝你的提問，朱利安。早安.我請 Rusty 回答這個問題。生鏽了嗎？

Yes. So let me clarify maybe a couple of things. So first, I think our view is that demand being rejected and us having to file this by supplement is the worst case scenario. We think what the FDA did was absolutely right accepting our amendment. So we don't think this will even come into play, but if we were required to come into a supplement, and that's exactly right. So if you look at the statute, again, it's 21 USC, 355 C3C, what specifically defines those patents that can give rise to a 30-month stay.

是的。因此，讓我澄清幾件事。因此首先，我認為我們的觀點是，需求被拒絕並且我們不得不透過補充文件提出這項要求是最糟糕的情況。我們認為 FDA 接受我們的修正案是完全正確的。因此，我們認為這甚至不會發揮作用，但如果我們被要求進行補充，那就完全正確了。因此，如果你看一下法規，你會發現它是 21 USC、355 C3C，其中具體定義了那些可以導致 30 個月暫停的專利。

And critically, it says only those patents and are quoted before the date on which the application. And then in [Treprostinil], excluding and amendments or supplements, the application was submitted. So again, supplements are treated the exact same way as amendments for purposes of determining which patents can give rise to a 30-month stay. And so even if we were required to file a supplement, the result would be no, new 30-month stay.

至關重要的是，它只提到了那些在申請日期之前被引用的專利。然後在[曲前列尼爾]中，排除和修改或補充，提交了申請。因此，在決定哪些專利可以享受 30 個月的暫緩期限時，補充專利與修正案的處理方式完全相同。因此，即使我們被要求提交補充文件，結果也是否定的，新的 30 個月停留期。

Very helpful. Thank you.

非常有幫助。謝謝。

Thank you, Julian. Operator, next question, please.

謝謝你，朱利安。接線員，請問下一個問題。

Serge Belanger, Needham.

塞爾吉·貝朗格，尼德漢姆。

Hi, good morning. Thanks for taking my question. I guess the first one, and apologies if I missed this in the prepared remarks, but has there been any additional interactions with the agency post the late January to do for dates for the PH-ILDs approval. Have they asked for additional information or giving you any additional information regarding their internal process for that potential approval?

嗨，早安。感謝您回答我的問題。我想是第一個問題，如果我在準備好的發言中遺漏了這一點，請原諒，但是在 1 月底之後是否與該機構進行過任何其他互動，以確定 PH-ILD 批准日期。他們是否要求提供更多資訊或向您提供任何有關其潛在批准內部流程的附加資訊？

And then secondly, I guess for Rusty, maybe just talk about the Supreme Court decision to denied Liquidia petitioned late last-month and just what it means to the overall legal proceedings? Thanks.

其次，我想對於 Rusty 來說，也許可以談談最高法院上個月末駁回 Liquidia 請求的決定，以及這對整個法律程序意味著什麼？謝謝。

Thanks, Serge. Good morning. I'll break this into two parts, so Rajeev oversees our regulatory group. You can answer the first question. We like regarding interactions with FDA and then Rusty, if you'll answer the Supreme Court question. Rajeev?

謝謝，Serge。早安.我會將其分為兩部分，以便 Rajeev 負責監督我們的監管小組。你可以回答第一個問題。我們喜歡與 FDA 以及 Rusty 互動，如果你願意回答最高法院的問題的話。拉吉夫？

Yeah. Thanks, Roger. Hi, Serge, good morning. I saw regards to on our -- we continue to believe very strongly as Rusty already alluded to that, the amendment we filed to add on the indication for PH-ILD remains appropriate and in line with our discussions with the FDA, as you know, the only stopping gap was really the [Concord facility], which if we had received previous approval, that lead to a tentative approval. Now we anticipate that data shortly arriving on May 31, from the Concord [inclusivity] end. And therefore, the entire package right now is will lead to now a full approval for both indications for PAH and PH-ILD. And we remain confident in that matter.

是的。謝謝，羅傑。你好，Serge，早安。我看到了關於我們的——我們仍然堅信，正如 Rusty 已經提到的那樣，我們提交的增加 PH-ILD 適應症的修正案仍然是適當的，並且符合我們與 FDA 的討論，如您所知，唯一的障礙實際上是 [Concord 設施]，如果我們之前已獲得批准，那麼這將導致暫時批准。現在我們預計資料將於 5 月 31 日從 Concord [包容性] 端很快到達。因此，目前的整個方案將導致 PAH 和 PH-ILD 兩種適應症的全面批准。我們對此仍然充滿信心。

I'll turn it over to Rusty to answer your second question.

我將把答案交給 Rusty 來回答您的第二個問題。

Serge, thanks for the question. So the Supreme Court case really has no bearing set, so as a reminder, that case was our attempt to overturn the original Hatch-Waxman decision on the 793 Patent and raise some arguments that we think, you overlooked by the lower court that there shouldn't have been a finding of infringement at all. It's very important take-up that appeal. But again, it all relates to the 793 Patent which separately has been invalidated at this point and our firms really twice by the Federal Circuit. So with that decision from the Federal Circuit, the decision of the Supreme Court really doesn't bear on how this is going to play out not at all.

塞爾吉，謝謝你的提問。因此，最高法院的案件實際上並沒有影響，所以提醒一下，該案件是我們試圖推翻關於 793 專利的原始 Hatch-Waxman 裁決，並提出一些我們認為下級法院忽略的論點，即根本不應該裁定侵權。接受這項訴求非常重要。但這一切都與 793 專利有關，該專利目前已被聯邦巡迴法院兩次宣告無效。所以，根據聯邦巡迴法院的判決，最高法院的判決其實與此事的結果沒有絲毫關係。

Thank you.

謝謝。

Yeah. Maybe, Serge, I'll just add a little bit to [Rusty]. So I think, the one communications we've had obviously we missed the January 24, to do the action date. And the reason for that has been communicated is that the FDA is waiting for the injunction to be removed. So as Rusty said, there's two things that need to happen principally for us to get full approval, which is the injunction removed and then the potential of the clinical exclusivity to expire at the end of March.

是的。也許，Serge，我只需要添加一點[生鏽]。因此我認為，我們所進行的一次溝通顯然使我們錯過了 1 月 24 日採取行動的日期。已經傳達的原因是 FDA 正在等待禁令被取消。正如 Rusty 所說，我們要想獲得完全批准，主要需要做兩件事，即取消禁令，然後臨床獨佔權有可能在 3 月底到期。

So as Rajeev said, we were looking now the amendment was filed and asked for full approval even when we filed it in July for both PAH and PH-ILD. So it's our expectation now that we'll skip the tentative approval phase and probably just go to a full approval after the March 31, clinical exclusivity expiration.

因此，正如 Rajeev 所說，我們現在正在考慮提交修正案，並要求獲得全面批准，即使我們在 7 月為 PAH 和 PH-ILD 提交了修正案。因此，我們現在的預期是，我們將跳過初步批准階段，並可能在 3 月 31 日臨床獨佔權到期後直接獲得全面批准。

Operator, next question, please.

接線員，請問下一個問題。

Matt Kaplan, Ladenburg Thalmann.

馬特卡普蘭、拉登堡塔爾曼。

Thank you. Good morning and Roger, just to follow up on that question in terms of -- and thank you Rusty for the detail. Play-by-play in terms of the moving parts here in litigation, but in terms of the critical path and Judge Andrews lifting on the injunction, can you give us some more detail in terms of the moving parts there and how that, that portion of their work? Obviously, their [regulatory] exclusivity expiration is just a date on the calendar. So that's easy.

謝謝。早安，Roger，我只是想跟進一下這個問題——感謝 Rusty 提供的詳細說明。就訴訟中的活動部分逐一介紹，但就關鍵路徑和安德魯斯法官解除禁令而言，您能否就其中的活動部分以及他們的這部分工作如何進行向我們提供更多細節？顯然，他們的（監管）獨家經營權到期只是日曆上的一個日期。這很容易。

Yeah. And I addressed, it can fill in here. But again, we feel the Andrew Judge is actually has only needs now that to route to remove the injunction. The December 20, affirmation by the Federal Circuit Court of Appeals should have given them the power to amendment again, I think he was just waiting to see the rehearing request denied and then the mandate to issue, which will happen next week. I think next Tuesday is when that should issue. So at that point here, really fully empowered to do what he needs to do, whether or not, I think rest of you can comment on how you see the pending PI how that interplay may impact this.

是的。而且我提到的那個，可以在這裡填寫。但我們再次認為，安德魯法官現在實際上只需要採取撤銷禁令的途徑。聯邦巡迴上訴法院 12 月 20 日的確認應該賦予他們再次修改的權力，我認為他只是在等待重新審理請求被駁回，然後發布命令，這將在下週發生。我認為下週二就會發布該消息。因此，在這一點上，他真的有充分的權力去做他需要做的事情，無論是否，我想你們其他人都可以評論一下你們如何看待待決的 PI，以及這種相互作用會如何影響這一點。

Yes. So Roger, on the existing injunction of what you laid out is exactly correct. Again, it's been fully briefed in front of Judge Andrews so that he has what he needs. We also yesterday supplemented, what we had submitted to him to provide them the denial to rehearing request that was issued by the Federal Circuit's again, yes, all the information in front of them. It's in obviously that they have the new case, the 327 Patent case where they've also requested a preliminary injunction. This cases really don't relate to one another on the books in front of the same judge and obviously the patent system similar. But procedurally, the injunction that currently exists isn't tied to their request for a new injunction on the new patent. So I don't think there's any interdependency there between the two actions.

是的。所以羅傑，你所列出的現有禁令是完全正確的。再次，我們已經向安德魯斯法官全面報告了情況，以便他了解所需資訊。我們昨天還補充了我們向他提交的材料，以向他們提供聯邦巡迴法院再次發布的拒絕重新審理請求的決定，是的，所有信息都擺在他們面前。顯然，他們有新的案件，即 327 專利案，他們也在該案中請求初步禁令。這些案件實際上在同一位法官面前審理，彼此之間沒有關聯，專利制度顯然也相似。但從程序上看，目前存在的禁令與他們對新專利的新禁令請求無關。因此我認為這兩項行動之間不存在任何相互依賴關係。

That's why we're not giving a specific date when we think the approval actually will happen. But again, other than it will be after March 31, when the exclusivity expires.

這就是為什麼我們沒有給出真正獲得批准的具體日期。但是，除此之外，獨家經營權將於 3 月 31 日到期之後才會恢復。

Right. Okay, great. And then shift gears a little bit in terms of L606, can you give us some more details in terms of the regulatory pathway there? You described needing one additional study for approval in both PAH and PH-ILD? What -- can you give us a sense in terms of the timeline of that as well?

正確的。好的，太好了。然後就 L606 稍微轉換主題，您能否向我們提供有關其監管途徑的更多細節？您描述過需要另外一項研究來獲得 PAH 和 PH-ILD 的批准嗎？什麼－您能為我們介紹一下這個時間軸的情況嗎？

Yeah, I'd love to. So Rajeev also overseeing that effort to. Rajeev, if you wouldn't mind answering the question.

是的，我很樂意。因此 Rajeev 也負責監督這項工作。Rajeev，如果你不介意的話，請回答這個問題。

Yeah. Thank you, Matt, and good morning to you as well. So as you alluded to on L606 or liposomal formulation of sustained relief for [three partner] that's going to be delivered twice a day with really a smart portable nebulizer. So we're really excited about this program as it's leading the effort to a Phase 3 program that the program is designed using a similar strategy like we have a YUTREPIA so this is a filer [5b2] pathway with the label drug being Tyvaso.

是的。謝謝你，馬特，也祝你早安。因此，正如您所提到的 L606 或脂質體製劑可以為 [三位合夥人] 提供持續緩解，每天將透過智慧型便攜式霧化器進行兩次給藥。因此，我們對這個項目感到非常興奮，因為它正在引領第 3 階段計劃的努力，該計劃的設計採用了類似的策略，就像我們的 YUTREPIA 一樣，所以這是一個申報 [5b2] 途徑，標籤藥物是 Tyvaso。

In our Type C discussions with FDA that have occurred back in December of 2023. Once again, we had confirmation that a single placebo efficacy study with L606, would lead to approval for both indications for Group 1 PAH as well as Group 3 PH-ILD. In that regard, as you stated we specifically have chosen the indication for PH-ILD to take into a global large Phase 3 study, that study is gated to initiate sometime into new Q4 of 2024.

在我們與 FDA 進行的 C 類討論中，早在 2023 年 12 月就進行了此類討論。我們再次確認，對 L606 進行的單一安慰劑療效研究將獲得針對第 1 組 PAH 以及第 3 組 PH-ILD 兩種適應症的批准。在這方面，正如您所說，我們特意選擇了 PH-ILD 作為適應症，以開展全球大型 3 期研究，該研究計劃於 2024 年第四季度的某個時候啟動。

Great. Thank you, Rajeev. And I think the one thing to add to that is, I guess the other part of your question is how long will that take? I think because there's such a scarcity of treatments for PH-ILD, the clinical trial, particularly when we do it in European centers, for instance, it has potential to enroll quite rapidly. I think in the normal time course, for the sample size we're contemplating would be two years or so. But I think maybe we can shorten that a bit and there's time to get through the six-month time endpoint and then time to collect the data submit and reviews. So I think just in broad brush strokes, we're looking at it from first patient into FDA decision is probably in the 3.5 to 4-year arrangement.

偉大的。謝謝你，拉吉夫。我認為需要補充的一點是，我猜你問題的另一部分是這需要多長時間？我認為，由於 PH-ILD 的治療方法非常稀缺，臨床試驗（特別是當我們在歐洲中心進行試驗時）有潛力迅速招募患者。我認為，在正常的時間過程中，我們考慮的樣本量應該是兩年左右。但我認為也許我們可以縮短一點時間，有時間度過六個月的時間終點，然後有時間收集資料提交和評論。因此，我認為，從大體上看，從第一位患者到 FDA 做出決定，可能需要 3.5 到 4 年的時間。

Next question, please. Operator?

請回答下一個問題。操作員？

Kambiz Yazdi, Jefferies.

坎比茲·亞茲迪（Kambiz Yazdi），傑富瑞（Jefferies）。

Good m,orning, team. With the filed motion for preliminary injunction with regard to 327, what would be the timelines associated with that.

早安，各位團隊。關於 327 的初步禁令動議已經提交，與之相關的時間表是怎樣的。

And then can you remind us the FDA's perspective of NDA real amendment versus NDA for indication expansion with regards to tentatively approved drugs? Do we have any precedence there? Thank you.

然後，您能否提醒我們 FDA 對暫時核准藥物的 NDA 真正修正與適應症擴大的 NDA 的看法？我們在那裡有任何先例嗎？謝謝。

Yeah. I think both of those questions are in Rusty courts. Have you in mind, Rusty?

是的。我認為這兩個問題都在 Rusty 法庭上。你介意嗎，拉斯蒂？

Sure. So on the first question, for the 327 Patent. So the there is a briefing schedule on that, United Therapeutics has filed their brief requesting in support of their request for a preliminary injunction. Our responses do currently due on April 5, at their reply them do April 19.

當然。第一個問題是關於 327 專利。因此有一個關於該問題的簡報時間表，聯合治療公司已經提交了簡短的請求，以支持他們的初步禁令請求。我們的回覆截止日期為 4 月 5 日，最晚回覆截止日期為 4 月 19 日。

The thing I'd add, and then from there, the court discussion of the hearing or not and makes a decision. The thing I'd remind you, though, is that again, the default is that if there's no preliminary injunction in place, there's nothing that blocks us from moving forward getting approval and launching. So the burdens on United Therapeutics to get a preliminary injunction before that happens. So we'll see if they're trying to accelerate the proceedings or what they're trying to do on that front, but that's the time line currently in place on that.

我想補充的是，然後從那裡開始，法庭將討論是否舉行聽證會並做出決定。不過，我要提醒你的是，預設情況下，如果沒有初步禁令，就沒有什麼可以阻止我們繼續獲得批准和啟動。因此，聯合治療公司有責任在那之前獲得初步禁令。因此，我們將看看他們是否試圖加快進程或他們試圖在這方面做些什麼，但這是目前的時間表。

As far as the FDA's position on amendments versus supplements. Again, I think if you look at the FDA existing guidance's, there's a 2004 nonbinding guidance. That is what United Therapeutics is point to which they claim stands for the proposition there. You can never add an amendment to a pending NDA -- I'm sorry, never had an indication to a pending NDA. However, the 2016 regulations in the site is 21 CFR, [314.60] Subsection F, expressly contemplates situations where new indications could be added to a pending NDA, including a [505b2] NDA like ours. So again, I think clearly the FDA is contemplating that there are early circumstances where indications can be added to NDA's, as evidenced by the regulations.

至於 FDA 對修正案與補充案的立場。再次，我認為如果你看看 FDA 現有的指南，你會發現有一份 2004 年的非約束性指南。這就是聯合治療公司 (United Therapeutics) 的觀點，他們聲稱這代表了該主張。您永遠無法對未決的保密協議 (NDA) 新增修訂 — — 抱歉，我們從未收到有關未決的保密協議 (NDA) 的跡象。然而，該網站中的 2016 年法規是 21 CFR，[314.60] F 小節，明確考慮了可以在待決 NDA 中添加新適應症的情況，包括像我們這樣的 [505b2] NDA。因此，我再次認為，FDA 顯然正在考慮在早期情況下可以將適應症添加到 NDA 中，正如法規所證明的那樣。

And if I may add in Acambis, I think the guidance that there that United Therapeutics is pointing towards is the bundling guidance, but that's really more specific in Europe, changing route dosage formulation and providing new data that should be submitted separately. And it's a way to make sure that the agency gets there reduces. We've done none of that. Same route, same dosage forms, same formulation and no new data. So we think we're well within that protection. The rest, Rusty just described.

如果我可以補充 Acambis，我認為 United Therapeutics 所指向的指導是捆綁指導，但這在歐洲確實更為具體，改變途徑劑量配方並提供應單獨提交的新數據。這是一種確保該機構能夠減少成本的方法。我們什麼都沒做。相同途徑、相同劑型、相同配方且沒有新數據。因此我們認為我們完全處於這種保護範圍內。其餘的，Rusty 只是描述了一下。

Great. Operating?

偉大的。操作？

I guess one other follow-up is on the ASCENT trial, what patient populations are being studied and how is the enrollment proceeding there?

我想另一個後續問題是有關 ASCENT 試驗的，該試驗研究的患者群體是什麼，以及招募工作進展如何？

Yeah. Great question. Appreciate that. Rajeev, If you wouldn't mind..

是的。好問題。非常感謝。Rajeev，如果你不介意的話...

Yeah. Thanks, Kambiz. So once again, the ASCENT study is something that we are extremely excited about. More importantly, this study that's absolutely needed in the literature and has actually been desired by the KOLs across the entire region of the United States requesting that patients that have been recently diagnosed with PH-ILD that are naive to any therapy are then placed onto YUTREPIA, which is, which really will highlight three pillars that we have continued to suggest, though that are very important to have patient profile.

是的。謝謝，Kambiz。因此，我們再一次對 ASCENT 研究感到非常興奮。更重要的是，這項研究在文獻中是絕對需要的，實際上也是美國整個地區的關鍵意見領袖所期望的，要求將最近被診斷為 PH-ILD 且未接受任何治療的患者納入 YUTREPIA，這將真正突出我們一直建議的三大支柱，儘管這些支柱對於了解患者資料非常重要。

First thing is titrated type of tolerability and titrate credibility. These things are going to be led by our PRINT technology and therefore formulation. The combination of those two allows us to use a very low resistance off-the-shelf inhaler, which has the simplicity that is needed for patients that have impairments in lung function but can deliver the dose profiles that we believe are going to be required to not only achieve the minimum therapeutic goals of equivalency of 10 to 12 breaths four times a day of inhaled treprostinil. But more importantly, lead to actually more improvements in clinical outcomes and efficacy standards that are used such as walk distance, I mean, actual overall clinical outcomes.

首先是滴定類型的耐受性和滴定的可信度。這些事情將由我們的 PRINT 技術和配方主導。兩者的結合使我們能夠使用阻力非常低的現成吸入器，這種吸入器具有肺功能受損患者所需的簡單性，但可以提供我們認為不僅達到每天四次吸入曲前列尼爾 10 至 12 次呼吸等效的最低治療目標所需的劑量。但更重要的是，實際上會進一步改善臨床結果和所使用的療效標準​​，例如步行距離，我的意思是實際的整體臨床結果。

We're very encouraged right now by the current enrollment rate that we're seeing, we enrolled our first patient at the mid to end of December of 2023, and we anticipate that we will complete enrollment up to 60 patients by the end of this year. So we look forward to sharing some snapshots of data in future meetings that are coming up shortly. Roger?

目前的入組率讓我們感到非常鼓舞，我們在 2023 年 12 月中旬至 12 月底入組了第一位患者，預計到今年年底將完成 60 名患者的入組。因此，我們期待在即將召開的會議上分享一些數據快照。羅傑？

Thank you, Rajeev. And I think, Kambiz, it's a great question. I think the other thing you know, again, what why this data is important. And I think if when you look at the data, that's some of the data that's been published on United Therapeutics has commenced the KPI, particularly the data at the National Jewish center in Colorado. You can see that there in some difficulty with the KPI in at least their single-center patient population, about 60% of their patients dropped off between three and six months, whether or not they were naive to perhaps items that were transitioned previously from nebulized.

謝謝你，拉吉夫。我認為，Kambiz，這是一個很好的問題。我認為您知道的另一件事是，為什麼這些數據很重要。我認為，如果您查看數據，您會發現聯合治療公司發布的一些數據已經開始了 KPI，特別是科羅拉多州國家猶太中心的數據。您可以看到，至少在單中心患者群體中，KPI 存在一些困難，大約 60％ 的患者在 3 到 6 個月之間退出，無論他們是否對先前從霧化過渡的項目不熟悉。

And I think the other thing that's interesting to us is that there's still a retained 40% population of nebulized patients. I think when you launched a few years ago, the assumption was that they would convert that entire market quite quickly database at KPI. So that's not happened. So the question is why and we think it may be for the inability to dose those patients to good clinical effect, which we're trying to solve for with YUTREPIA.

我認為另一件讓我們感興趣的事情是，仍然有 40% 的霧化患者。我認為當你幾年前推出時，假設他們能夠很快地將整個市場資料庫轉換為 KPI。所以那件事並沒有發生。所以問題是為什麼呢？ 我們認為這可能是因為無法給這些患者服用藥物以達到良好的臨床效果，我們正在嘗試透過 YUTREPIA 來解決這個問題。

So if this data bears out the way we think it will, then that will certainly augur that this is the best-in-class therapy and first-in-choice therapy.

因此，如果這些數據證實了我們的想法，那麼這無疑預示著這是同類最佳的治療方法和首選治療方法。

Next question, please.

請回答下一個問題。

I'm showing no further questions and I'd like to hand the conference back over to Roger Jeffs for further remarks.

我沒有其他問題，我想將會議交還給羅傑·傑夫斯以進行進一步發言。

Great. Thanks, operator. So with no further questions, again, we thank you for joining us today. my sincere hope is that the next time we address you on the earnings call, liquidity will be prescribing to patients. What we feel is the preferred product, our in-house resource now and it will come at a critical time as the market for inhale treprostinil rapidly expand. Thank you, have a good day.

偉大的。謝謝，接線生。因此，沒有其他問題了，我們再次感謝您今天的參與。我真誠地希望，下次我們在收益電話會議上向你們致辭時，流動性將為患者開出處方。我們認為這是首選產品，也是我們現在的內部資源，它將在吸入曲前列尼爾市場迅速擴張的關鍵時刻到來。謝謝，祝你有美好的一天。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。