Liquidia Corp (LQDA) 2023 Q2 法說會逐字稿

Good morning, and welcome, everyone, to the Liquidia Corporation Second Quarter 2023 Financial Results and Corporate Update Conference Call. My name is Olivia, and I will be your conference operator today. (Operator Instructions). I would like to remind everyone that this conference call is being recorded. I will now hand the conference call over to Jason Adair, Chief Business Officer.

早上好，歡迎大家參加 Liquidia Corporation 2023 年第二季度財務業績和公司最新動態電話會議。我叫奧利維亞，今天我將擔任你們的會議操作員。 （操作員說明）。我想提醒大家，這次電話會議正在錄音。我現在將電話會議交給首席商務官 Jason Adair。

Thank you, Olivia. It's my pleasure to welcome everyone to Liquidia's Second Quarter 2023 Financial Results and Corporate Update Call. Joining the call today are Chief Executive Officer, Dr. Roger Jeffs; Chief Financial Officer, Michael Kaseta; General Counsel, Rusty Schundler; and Chief Medical Officer, Dr. Rajeev Saggar. 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.

謝謝你，奧利維亞。我很高興歡迎大家參加 Liquidia 2023 年第二季度財務業績和公司最新情況電話會議。今天加入電話會議的還有首席執行官 Roger Jeffs 博士；首席財務官 Michael Kaseta；總法律顧問 Rusty Schundler；首席醫療官 Rajeev Saggar 博士。在我們開始之前，請注意，今天的電話會議將包含前瞻性聲明，包括有關未來業績、未經審計和前瞻性財務信息以及公司未來業績和/或成就的聲明。

These statements are subject to known and unknown risks and uncertainties, which may cause 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. I'd now like to turn the call over to Roger for our prepared remarks, after which he will open the call up for your questions.

這些陳述受到已知和未知的風險和不確定性的影響，這可能導致實際結果或業績與本次電話會議中明示或暗示的任何未來結果或業績存在重大差異。有關更多信息，包括對我們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，這些文件可以在我們的網站上訪問。現在我想將電話轉給羅傑，讓他聽取我們準備好的發言，之後他將打開電話詢問你們的問題。

Good morning, everyone, and thank you for joining us. In our opening remarks today, we're going to take a very focused approach to address the issue that is most top of mind for our company, our employees and our shareholders. Specifically, the path forward as we see it to the successful resolution of the litigation and launch of YUTREPIA for both PAH and PH-ILD.

大家早上好，感謝您加入我們。在今天的開場白中，我們將採取非常有針對性的方法來解決我們公司、員工和股東最關心的問題。具體來說，我們認為成功解決訴訟並為 PAH 和 PH-ILD 推出 YUTREPIA 的前進道路。

I will note, however, that in addition to the significant legal derisking that Rusty will talk about shortly, we also achieved other major and important milestones in the quarter most notably, the license of L606, a Phase III clinical program for twice-daily liposomal formulation of inhaled treprostinil that positions us with the best-in-class portfolio of inhaled treprostinil products to best address patient needs, not only today but also in the future.

然而，我要指出的是，除了Rusty 將很快談到的重大法律風險之外，我們在本季度還實現了其他重大和重要的里程碑，最引人注目的是L606 的許可，這是一項每日兩次脂質體的III 期臨床項目吸入曲前列環素的配方使我們能夠擁有一流的吸入曲前列環素產品組合，以最好地滿足患者的需求，不僅在今天，而且在未來。

As mentioned, the bulk of our prepared remarks will focus on the recent legal and regulatory actions related to the ongoing litigation. I've asked Rusty to elaborate on 4 specific points. First, the favorable affirmation by the Federal Circuit that we do not infringe any valid claims of the '066 patent.

如前所述，我們準備的發言大部分將集中於與正在進行的訴訟相關的近期法律和監管行動。我請 Rusty 詳細闡述了 4 個具體點。首先，聯邦巡迴法院有利地確認我們沒有侵犯'066 專利的任何有效權利要求。

Second, our confidence that United's attempt to overturn the PTAB's decision on the '793 patent will fail. Third, the positive impact in submitting an amendment to add the PH-ILD indication to YUTREPIA's label. And lastly, our confidence in why we feel that the recently allowed patent claims to United Therapeutics related to the treatment of PH-ILD, will not be an impediment to YUTREPIA. Rusty?

其次，我們相信美聯航推翻 PTAB 對 '793 專利的決定的嘗試將會失敗。第三，提交修正案以在YUTREPIA標籤中添加PH-ILD指示的積極影響。最後，我們相信為什麼我們認為最近獲得批准的聯合治療公司與 PH-ILD 治療相關的專利主張不會成為 YUTREPIA 的障礙。生鏽了？

Thank you, Roger. As a reminder, Liquidia has been partied to 2 separate appeal proceedings at the Federal Circuit that are relevant to the launch of YUTREPIA. Broadly speaking, the appeals related to 2 patents asserted against Liquidia. The '066 Patent, which describes a way of making and storing treprostinil and the '793 Patent, which describes the method of use to treat patients with pulmonary hypertension.

謝謝你，羅傑。需要提醒的是，Liquidia 已參與聯邦巡迴法院的 2 項獨立上訴程序，這些程序與 YUTREPIA 的推出相關。從廣義上講，上訴涉及針對 Liquidia 主張的 2 項專利。 '066 專利描述了曲前列環素的製造和儲存方法，'793 專利描述了治療肺動脈高壓患者的方法。

Before walking through the recent decisions and activities, I would like to point out that our guidance over the last 12 months is still the same. We believe the ongoing litigation will be concluded between the end of 2023 and in the middle of 2024, clearing the path to final approval and launch of YUTREPIA. The only thing that has changed in the last year is our increased confidence in our guidance with each legal decision. Now moving to the recent decision.

在詳細介紹最近的決定和活動之前，我想指出，我們過去 12 個月的指導方針仍然相同。我們相信正在進行的訴訟將於 2023 年底至 2024 年中期結束，為 YUTREPIA 的最終批准和推出掃清道路。去年唯一改變的是我們對每項法律決定的指導信心增強。現在轉向最近的決定。

On July 24, the Federal Circuit affirmed the District Court's decision from last August in the Hatch-Waxman litigation. The outcome of the appeal was in line with our expectations, meaning 5 of 6 claims in the and '066 Patent, were affirmed as obvious, unpatentable and as invalid and the YUTREPIA does not infringe the single valid '066 Patent claim that was asserted against us.

7 月 24 日，聯邦巡迴法院維持了地方法院去年 8 月在 Hatch-Waxman 訴訟中的裁決。上訴結果符合我們的預期，這意味著 和 '066 專利中的 6 項權利要求中的 5 項被確認為顯而易見、不可專利且無效，並且 YUTREPIA 並未侵犯針對 '066 專利的單一有效權利要求我們。

The Federal Circuit also affirmed that YUTREPIA infringes the asserted claims of the '793 Patent and that based solely on the arguments presented in the Hatch-Waxman litigation, the '793 Patent is valid. However, the court also commented in the written decision that the court is aware that the Patent Trial and Appeal Board or PTAB, has found all of the claims of the '793 Patent to be unpatentable.

聯邦巡迴法院還確認 YUTREPIA 侵犯了 '793 專利所主張的權利要求，並且僅根據 Hatch-Waxman 訴訟中提出的論點，'793 專利是有效的。然而，法院還在書面判決中評論說，法院知道專利審判和上訴委員會或 PTAB 已發現 '793 專利的所有權利要求均不具有專利性。

And that the PTAB decision is on appeal, which I will discuss shortly. As we've noted previously, should the PTAB decision be affirmed on appeal, the '793 Patent would be completely invalidated and all previous rulings related to the alleged infringement of the '793 Patent would be dissolved. Liquidia would then be free to seek final approval from the FDA for YUTREPIA.

PTAB 的決定正在上訴，我將很快討論這一點。正如我們之前指出的，如果 PTAB 的裁決在上訴中得到維持，'793 專利將完全無效，之前所有與涉嫌侵犯 '793 專利相關的裁決都將被撤銷。然後，Liquidia 將可以自由地尋求 FDA 對 YUTREPIA 的最終批准。

As next steps with respect to the Federal Circuit ruling, it is possible that one or both parties could seek a rehearing by the 3-judge panel and/or a hearing on bond in front of the full Federal Circuit. One of both parties could also file for cert with the United States Supreme Court. However, we see nothing in the Federal Circuit's decision regarding the '066 Patent that we believe is likely to lead to any further rehearing or cert being granted.

作為聯邦巡迴法院裁決的下一步，一方或雙方可能會尋求由 3 名法官組成的小組進行重審和/或在整個聯邦巡迴法院舉行保釋聽證會。雙方之一也可以向美國最高法院申請認證。然而，我們認為聯邦巡迴法院關於 '066 專利的決定中沒有任何內容可能導致任何進一步的複審或授予證書。

Even if a rehearing or cert is granted, it is important to remember that all 4 judges who have rolled on the '066 Patent, between the District Court and Federal Circuit have found the '066 patent claims to be invalid or not infringed. Regardless, our ability to seek final approval for YUTREPIA is not contingent on the conclusion of rehearing or appeal of the affirmed Hatch-Waxman decision. The proceeding that is currently limiting our ability to see final approval for YUTREPIA is United's appeal of the PTAB's decision, which invalidates the '793 Patent, which I mentioned briefly earlier.

即使獲得了重審或認證，重要的是要記住，地方法院和聯邦巡迴法院之間審理 '066 專利的所有 4 名法官均發現 '066 專利權利要求無效或未侵權。無論如何，我們尋求 YUTREPIA 最終批准的能力並不取決於重審的結論或對已確認的 Hatch-Waxman 決定的上訴。目前限制我們獲得 YUTREPIA 最終批准的程序是美聯航對 PTAB 決定的上訴，該決定使我之前簡要提到的 '793 專利無效。

To summarize, all of the '793 Patent claims have been ruled by the PTAB to be on unpatent. Their first ruling was in July 2022. The merits of Liquidia's arguments were further reinforced in February 2023, when the PTAB denied United's request for rehearing and reaffirm that all of the claims are obvious over publicly accessible prior art. In April, United appealed the PTAB's decision to the Federal Circuit. And briefing should be completed in the 4th quarter of this year.

總而言之，所有 '793 專利權利要求均已被 PTAB 裁定為非專利。他們的首次裁決是在2022 年7 月。Liquidia 的論點在2023 年2 月得到進一步強化，當時PTAB 拒絕了美聯航的重審請求，並重申所有主張相對於可公開獲取的現有技術都是顯而易見的。 4 月，美聯航就 PTAB 的決定向聯邦巡迴法院提起上訴。簡報應在今年第四季度完成。

Once briefing is completed, the Federal Circuit has ordered oral arguments to be scheduled on the next available date in its calendar, which we expect to be in the late 4th quarter of 2023 to early 2024. Once heard, the Federal Circuit could issue its ruling by 1 of 2 procedures. First, the court could issue a simple summary affirmance of the PTAB's decision within a few days after oral argument. Or second, the court could issue a full written opinion, in which case, we would anticipate likely receiving the decision within a few months after oral argument, similar to the timing of the Hatch-Waxman appeal decision. We will not predict which of these decision paths is unlikely.

簡報完成後，聯邦巡迴法院已下令在其日曆中的下一個可用日期安排口頭辯論，我們預計該日期為 2023 年第四季度末至 2024 年初。聽證會後，聯邦巡迴法院可以發布裁決通過2 個過程中的1 個。首先，法院可以在口頭辯論後幾天內發布對 PTAB 決定的簡單摘要確認。其次，法院可以發布完整的書面意見，在這種情況下，我們預計可能會在口頭辯論後幾個月內收到裁決，類似於哈奇-韋克斯曼上訴裁決的時間安排。我們不會預測這些決策路徑中哪一條不太可能。

However, whenever a favorable decision is issued, Liquidia will immediately seek final regulatory approval for YUTREPIA. With these time frames in mind, we continue to believe that the ongoing litigation will be concluded sometime between late 2023 and early 2024. I'd like to turn now to the amended NDA that Liquidia submitted to request the addition of the PH-ILD indication to the proposed label for YUTREPIA. The amendment was filed on July 24, the same day that we received the decision in the Hatch-Waxman appeal.

然而，每當發布有利的決定時，Liquidia 將立即尋求 YUTREPIA 的最終監管批准。考慮到這些時間框架，我們仍然相信正在進行的訴訟將在 2023 年底至 2024 年初之間的某個時間結束。我現在想談談 Liquidia 提交的修訂後的 NDA，以請求添加 PH-ILD 指示到YUTREPIA的擬議標籤。該修正案於 7 月 24 日提交，同一天我們收到了 Hatch-Waxman 上訴的裁決。

Due to the nature of the amendment, we were required to issue a second Paragraph IV notice that certified as of the date of the submission that the 6 patents listed for Tyvaso in the Orange Book are invalid and/or not infringed by YUTREPIA. Three of those patents, the '066, '901 and '793 patents are the same 3 patents that have been litigated over the last several years and has been found to be invalid or not infringed by YUTREPIA. The other 3 patents in the Orange book for Tyvaso are directed specifically to the nebulized delivery of treprostinil are completely unrelated to YUTREPIA, and we're not asserted against Liquidia in the original Hatch-Waxman litigation.

由於修正案的性質，我們需要發布第二份第四段通知，證明截至提交之日，橙皮書中列出的 Tyvaso 的 6 項專利無效和/或未被 YUTREPIA 侵犯。其中三項專利，即“066”、“901”和“793”專利，與過去幾年中受到訴訟並已被認定為無效或未被 YUTREPIA 侵犯的 3 項專利相同。 Tyvaso 橙皮書中的其他 3 項專利專門針對曲前列環素的霧化給藥，與 YUTREPIA 完全無關，而且我們在最初的 Hatch-Waxman 訴訟中並未針對 Liquidia 提出主張。

Although it is possible that United could file a new Hatch-Waxman, possibly based on this amended NDA. The existing Federal Circuit decisions on this '066 and '901 patents and the future favorable affirmant of the PTAB's in validation of the '793 Patent would be binding once finalized on appeal. Under well settled legal principles, United cannot maintain a second lawsuit for infringement of the same old patents against the same YUTREPIA products even if the new lawsuit is filed and a new 30-month stay at the FDA is triggered, that lawsuit would effectively end upon completion of the '793 appeal because all issues in the new lawsuit would have been decided and in binding at that time. Thus, although it is possible that the amended NDA could trigger further litigation from United, we do not anticipate any material change to our time line.

儘管曼聯有可能根據修訂後的保密協議提交新的 Hatch-Waxman 申請。一旦上訴最終確定，聯邦巡迴法院對該 '066 和 '901 專利的現有裁決以及 PTAB 對 '793 專利有效性的未來有利肯定將具有約束力。根據既定的法律原則，United 不能就同一 YUTREPIA 產品侵犯相同舊專利提起第二次訴訟，即使提起新訴訟並觸發 FDA 新的 30 個月的中止，該訴訟將有效結束'793 上訴已完成，因為新訴訟中的所有問題均已在當時得到裁決並具有約束力。因此，儘管修訂後的保密協議可能會引髮美聯航的進一步訴訟，但我們預計我們的時間表不會發生任何重大變化。

Finally, I want to address the new patent claims of the United at the end of June, which cover the treatment of PH-ILD patients with inhaled treprostinil. We expect the patent will issue in the coming weeks and likely be added to the Orange book for Tyvaso. Two main questions we have received have been: a, how do these claims impact the FDA's approval of YUTREPIA for PH-ILD; and b, how could the USPTO grant these plans, given the unpatentability of the '793 claims to treat patients with all forms of pulmonary hypertension. I will address each of these in turn.

最後，我想談談美國在 6 月底提出的新專利主張，其中涵蓋了吸入曲前列環素治療 PH-ILD 患者的情況。我們預計該專利將在未來幾週內發布，並可能被添加到 Tyvaso 的橙皮書中。我們收到的兩個主要問題是：a、這些聲明如何影響 FDA 批准 YUTREPIA 治療 PH-ILD； b，考慮到“793”號聲稱治療所有形式的肺動脈高壓患者的權利要求不具有專利性，美國專利商標局如何批准這些計劃。我將依次討論這些問題。

As the first question, it is important to note that because the new patent was not listed in the Orange book at the time we submitted our NDA amendment, there will be no 30-month stay at the FDA that attaches to this new patent. While we expect United may file a lawsuit alleging that Liquidia infringes this new patent, we would not automatically be delayed in our ability to seek final approval for the PH-ILD indication. Instead, the burden would be on United to seek and prevail in obtaining a preliminary injunction. To do so, the burden would be on United to demonstrate, among other things, that they are substantially likely to prevail on the merits of the case.

作為第一個問題，值得注意的是，由於在我們提交 NDA 修正案時，新專利尚未列入橙皮書，因此該新專利不會在 FDA 停留 30 個月。雖然我們預計美聯航可能會提起訴訟，指控 Liquidia 侵犯這項新專利，但我們不會自動推遲尋求 PH-ILD 適應症最終批准的能力。相反，曼聯有責任尋求並最終獲得初步禁令。為此，曼聯有責任證明，除其他外，他們很有可能根據案件的是非曲直獲勝。

Historically, the courts have generally declined to grant preliminary injunctions in situations where there are substantial questions as to the validity of the patented issue. This brings us to the second question, how could the USPTO grant these claims, given the unpatentability of the '793 claims to treat all of pulmonary hypertension. As you know, we cannot reveal the details of our legal positions. That being said, we strongly believe that this new path will be found to be valid because of substantial prior art to predate the priority date of this new patent application and fully anticipates all of these new patent claims.

從歷史上看，在專利問題的有效性存在重大問題的情況下，法院通常拒絕授予初步禁令。這給我們帶來了第二個問題，考慮到治療所有肺動脈高壓的“793”權利要求不可獲得專利，美國專利商標局如何批准這些權利要求。如您所知，我們無法透露我們法律立場的細節。話雖這麼說，我們堅信這條新途徑將被認為是有效的，因為大量的現有技術早於該新專利申請的優先權日期，並且充分預見了所有這些新專利權利要求。

For example, the '793 patent itself, which was filed in 2007 and predates this new patent implication by more than 10 years, already covers and discloses the same treatment of treprostinil to patients with all groups of pulmonary hypertension, including PH-ILD, as United itself has argued in the court. In addition, over the last 10 to 15 years, many physicians have conducted and published studies and analysis regarding the treatment of PH-ILD patients with treprostinil, including inhaled treprostinil, in fact, our own Chief Medical Officer, Rajeev Saggar, explored the use of treprostinil to treat PH-ILD patients almost 15 years ago, measuring the same basic endpoints that are identified in this new set of patent claims.

例如，'793 專利本身於 2007 年提交，比該新專利含義早了 10 多年，它已經涵蓋並公開了曲前列環素對所有肺動脈高壓患者（包括 PH-ILD）的相同治療方法，如聯合航空本身也在法庭上進行了辯護。此外，在過去的10到15年裡，許多醫生進行並發表了關於曲前列環素治療PH-ILD患者的研究和分析，包括吸入曲前列環素，事實上，我們自己的首席醫療官Rajeev Saggar探索了曲前列環素的使用大約 15 年前，曲前列環素用於治療 PH-ILD 患者，測量的基本終點與這組新專利權利要求中確定的基本終點相同。

A great many of these publications predate United's new patent applications by a number of years and constitute prior year art to the new patent. Ultimately, this new patent will likely be litigated, but it is fundamental to patent law that a patent that is not novel and covers methods of treatment that were already widely known will not be valid. Accordingly, we strongly believe this new patent will not affect Liquidia's ability to commercialize YUTREPIA. In summary, the merits of Liquidia's arguments remain sound, and if affirmed, will open the door to treating patients in the near future and we do not view this new patent as having any impact on that result. I'll now pass the call on to Mike to briefly address our financial reporting. Mike?

其中許多出版物早於美聯航的新專利申請許多年，並構成了新專利的前一年技術。最終，這項新專利可能會受到訴訟，但專利法的基礎是，一項不新穎且涵蓋已廣為人知的治療方法的專利將無效。因此，我們堅信這項新專利不會影響 Liquidia 將 YUTREPIA 商業化的能力。總而言之，Liquidia 的論點的優點仍然是合理的，如果得到證實，將為在不久的將來治療患者打開大門，我們認為這項新專利不會對該結果產生任何影響。現在我將把電話轉給邁克，簡要介紹一下我們的財務報告。麥克風？

Thank you, Rusty, and good morning, everyone. Our second quarter 2023 financial results can be found in the press release and the 10-Q filed this morning. Broadly speaking, the company continues to execute and manage its business activity with financial discipline in mind. We ended the second quarter with $88.2 million in cash, equating to a net burn of only $5.1 million over the first 6 months of this year. During the quarter, revenue from treprostinil injection increased $0.9 million compared to the same quarter last year due to favorable gross to net charge back and rebate adjustments, while cost of sales remained flat at $0.7 million.

謝謝你，Rusty，大家早上好。我們的 2023 年第二季度財務業績可在今天早上提交的新聞稿和 10-Q 中找到。從廣義上講，公司繼續在執行和管理其業務活動時牢記財務紀律。截至第二季度末，我們的現金為 8820 萬美元，相當於今年前 6 個月的淨消耗僅為 510 萬美元。本季度，由於有利的總淨額退款和回扣調整，曲前列環素注射液的收入與去年同期相比增加了 90 萬美元，而銷售成本則保持在 70 萬美元不變。

R&D expenses in the quarter increased $12.5 million compared to second quarter 2022, primarily due to the $10 million upfront payment tied to licensing North American rights to L606 from Pharmosa Biopharm, an expense which has been offset by the recent (technical difficulty) The increase of $2.3 million or 33% (technical difficulty) increased stock-based compensation expense.

與2022 年第二季度相比，本季度的研發費用增加了1250 萬美元，主要是由於與Pharmosa Biopharm 授權L606 的北美權利相關的1000 萬美元預付款，該費用已被最近（技術難度）的增加所抵消。股票補償費用增加 230 萬美元，即 33%（技術難度）。

Overall, the company remains well positioned financially through the key value-creating milestones tied to the resolution of the litigation. We are preparing to launch YUTREPIA with speed, building a pipeline with new product and remain opportunistic in our ability to create value going forward. With that, I'd like to now turn the call back over to Roger.

總體而言，通過與解決訴訟相關的關鍵價值創造里程碑，該公司在財務上仍然處於有利地位。我們正準備快速推出 YUTREPIA，建立新產品的管道，並在未來創造價值的能力方面保持機會主義。有了這個，我現在想把電話轉回給羅傑。

Thank you, Mike. And thank you, Rusty, for clearly articulating why the merits of our case give us great confidence. And importantly, while we anticipate our time line for legal clarity to remain as we have been saying, specifically between the end of 2023 and mid-2024. With that, I would now like to open the call for questions. Operator, first question, please.

謝謝你，邁克。感謝您，Rusty，您清楚地闡明了為什麼我們的案例的優點給了我們很大的信心。重要的是，儘管我們預計法律明確性的時間表將保持不變，特別是在 2023 年底至 2024 年中期之間。現在我想開始提問。接線員，第一個問題。

(Operator Instructions) Our first question coming from the line of Greg Harrison with Bank of America.

（操作員說明）我們的第一個問題來自美國銀行的格雷格·哈里森 (Greg Harrison)。

This is Mary Kate, on for Greg. I guess looking at L606 here, where do you see this fitting into the treatment paradigm for PAH and PH-ILD, and do you think there are certain patients who will likely prefer this to a DPI?

這是瑪麗·凱特，替格雷格發言。我想看看這裡的 L606，您認為這在哪裡適合 PAH 和 PH-ILD 的治療範例，您認為某些患者可能會更喜歡這種方法而不是 DPI？

We appreciate the question. Rajeev, if you would, please answer that.

我們感謝這個問題。 Rajeev，如果你願意的話，請回答這個問題。

Yes, Ann Mary Kate. So a few things about L606. Remember, this is a liposomal formulation of treprostinil that has been purposely designed to have extended pharmacokinetic plasma levels over a course of 12 hours. Because of these attributes, it's also purposely designed to show a lower Cmax by relative to 8x lower than Type A. So we believe this is very important because we believe this negates some of the core side effects that we see with peak plasma exposures with Tyvaso, but still maintaining a similar AUC.

是的，安·瑪麗·凱特。關於 L606 的一些事情。請記住，這是曲前列環素的脂質體製劑，經過專門設計，可在 12 小時內延長藥代動力學血漿水平。由於這些屬性，它還經過專門設計，顯示出較低的Cmax，比A 型低8 倍。因此，我們認為這非常重要，因為我們相信這可以消除我們在Tyvaso 峰值血漿暴露中看到的一些核心副作用，但仍保持相似的 AUC。

So essentially, what this allows for is a very sort of consistent, stable 24-hour exposure or twice a day dosing, which we believe is -- if you understand the last since 2009, Tyvaso is delivered 4 times a day. And remember, dosing is not provided during usually the sleeping hours. So we provide a complete 24-hour coverage. We anticipate that as we run through the clinical studies, this will be really taken up both in PAH and PH-ILD as a best in choice process. I think because of these clinical attributes. Roger?

因此，從本質上講，這實現了一種非常一致、穩定的24 小時暴露或每天兩次給藥，我們相信，如果您了解自2009 年以來的最後一次給藥，泰瓦索每天給藥4次。請記住，通常在睡眠時間內不提供給藥。所以我們提供完整的24小時覆蓋。我們預計，當我們進行臨床研究時，這將真正成為 PAH 和 PH-ILD 的最佳選擇過程。我認為是因為這些臨床特徵。羅傑？

Next question.

下一個問題。

(Operator Instructions) And our next question coming from the line of Julian Harrison with BTIG.

（操作員說明）我們的下一個問題來自 BTIG 的 Julian Harrison。

First, just to confirm some of your prepared remarks, United's new PH-ILD patent does not preclude your ability to seek final FDA approval for YUTREPIA and PH-ILD. Did I understand that correctly?

首先，為了確認您準備好的一些言論，United 的新 PH-ILD 專利並不排除您尋求 FDA 對 YUTREPIA 和 PH-ILD 最終批准的能力。我理解正確嗎？

Yes, Russ, do you want to address that?

是的，拉斯，你想解決這個問題嗎？

Sure. So I think there are -- that's correct, unless United was to obtain a preliminary injunction. So I think as I commented on previously, there would be no 30-month stay that would attach to this new patent, and so we would not be automatically prevented from obtaining approval for PH-ILD instead the burden would be on United to obtain a preliminary injunction. And for the reasons noted during the prepared remarks, we think they'll have a hurdle to overcome to obtain that preliminary injunction.

當然。所以我認為這是正確的，除非曼聯要獲得初步禁令。因此，我認為正如我之前評論的那樣，這項新專利不會有30 個月的中止期限，因此我們不會自動阻止獲得PH-ILD 的批准，而是由美聯航承擔獲得PH-ILD 批准的責任。初步禁令。由於在準備好的發言中指出的原因，我們認為他們需要克服一個障礙才能獲得初步禁令。

Okay. Great. Thanks for clarifying that. And then can you just remind us of your clinical development plan in PH-ILD, you don't need clinical data for approval here, but I'm curious what data points you think would be most helpful to characterize for the medical community. And generally speaking, are you able to comment on the time line there?

好的。偉大的。感謝您澄清這一點。然後您能否提醒我們一下您在 PH-ILD 方面的臨床開發計劃，您不需要臨床數據來批准這裡，但我很好奇您認為哪些數據點對醫學界描述最有幫助。總的來說，您能評論一下那裡的時間線嗎？

Yes. So that's correct, Julian. I'll answer the first part. We do not need any additional data to add PH-ILD to the label. And Rajeev, if you want to talk about the Phase IV type like studies that we're doing, if you will, to better inform the community about the use of YUTREPIA in PH-ILD patients.

是的。所以這是正確的，朱利安。我來回答第一部分。我們不需要任何額外數據即可將 PH-ILD 添加到標籤中。 Rajeev，如果您想談談我們正在進行的 IV 期研究，以便更好地向社區通報 YUTREPIA 在 PH-ILD 患者中的使用情況。

Sure. Thanks for the question. Yes, just to reiterate what Roger is saying, the guidance that the FDA has provided us in the past highlight the fact that we do not need any new clinical study for amending the application for PH-ILD. In regards to YUTREPIA, we believe that one of the biggest unanswered questions is the use of a dry powder formulation of treprostinil in these patients with PH-ILD.

當然。謝謝你的提問。是的，只是重申 Roger 所說的，FDA 過去向我們提供的指導強調了這樣一個事實：我們不需要任何新的臨床研究來修改 PH-ILD 的申請。關於 YUTREPIA，我們認為最大的未解決問題之一是在這些 PH-ILD 患者中使用曲前列環素乾粉製劑。

Remember, Tyvaso was originally approved using the nebulizer. So we believe studying that in a prospective open-label fashion will definitely provide some of these unanswered questions about the utility of YUTREPIA, especially given through our low resistance inhaler. These will answer several clinical questions. One, we believe this will highlight our improved tolerability profile, which we saw in our INSPIRE study in PAH, and we believe we anticipate similar outcomes. This is also highlight our ability to titrate the drug to higher doses, which we believe is important to continue to show improved clinical improvements in basic endpoints such as walk distance.

請記住，Tyvaso 最初被批准使用霧化器。因此，我們相信，以前瞻性的開放標籤方式進行研究肯定會提供一些有關 YUTREPIA 效用的未解答的問題，特別是通過我們的低阻力吸入器給出的問題。這些將回答幾個臨床問題。第一，我們相信這將凸顯我們耐受性的改善，正如我們在 PAH 的 INSPIRE 研究中看到的那樣，我們相信我們預計會出現類似的結果。這也凸顯了我們將藥物滴定至更高劑量的能力，我們認為這對於繼續顯示步行距離等基本終點的臨床改善非常重要。

Again, we believe these patients would benefit from a more portable device such as YUTREPIA. So we believe all those facets are going to be extremely well perceived by the PAH community. And in regards to the study, we still believe that we are -- we have noted before that the study will initiate near the end of 2023, specifically in the United States.

我們再次相信這些患者將受益於 YUTREPIA 等更便攜的設備。因此，我們相信 PAH 社區將會非常清楚地認識到所有這些方面。關於這項研究，我們仍然相信我們之前已經指出，這項研究將於 2023 年底啟動，特別是在美國。

Next question, please, operator.

接線員，請下一個問題。

Our next question coming from the line of Serge Belanger with Needham.

我們的下一個問題來自 Serge Belanger 和 Needham 的對話。

Just a couple of questions. I guess the first one on the recently filed NDA amendment for the PH-ILD indication. Just wondering about the next steps? Is it kind of the standard FDA acceptance within 60 days, and do you expect extensive approval from the FDA? I think you've talked about a 6-month review process.

只是幾個問題。我猜第一個是最近提交的針對 PH-ILD 適應症的 NDA 修正案。只是想知道接下來的步驟嗎？這是 FDA 在 60 天內接受的標準嗎？您是否期望獲得 FDA 的廣泛批准？我想你已經談到了 6 個月的審查過程。

The 30-day clock before they will indicate to us whether it's a type 1 or type 2 submission. Type 1 would be granted a 2-month review, and the type 2 submission would be granted a 6-month review. We feel that it could be a type 1 resubmission.

他們之前的 30 天時鐘將向我們表明提交的是類型 1 還是類型 2。類型 1 將獲得 2 個月的審查時間，類型 2 的提交將獲得 6 個月的審查時間。我們認為這可能是類型 1 重新提交。

But again, we'll just wait to see what the agency says because the 30 days will come up in mid-October. But the good news there is then we would get potentially tentative approval for PH-ILD as early as October or as late as early 2024, which, again, we would be prohibited from launching into that indication until the users market exclusivity ends in March of '24. But that's the basic time line. I think the other thing to point out, Serge, and the question is that the tentative approval for PAH remains, this is just an amendment to that tentative approval for PAH seeking tentative approval at this time for PH-ILD.

但我們還是要等待該機構的回應，因為 30 天的期限將在 10 月中旬到來。但好消息是，我們最早可能在 10 月或最遲 2024 年初獲得 PH-ILD 的初步批准，同樣，我們將被禁止推出該適應症，直到用戶市場獨占權於 2020 年 3 月結束。 '24。但這是基本的時間線。我認為另一件事要指出，Serge，問題是 PAH 的暫定批准仍然存在，這只是對 PAH 暫定批准的修正案，目前正在尋求 PH-ILD 的暫定批准。

Okay. And just thinking ahead of YUTREPIA, lauch, do you see the opportunity here as a kind of switching from Tyvaso or it would be more of new patient starts that would begin with YUTREPIA? And does that differ between PAH and PH-ILD?

好的。就在 YUTREPIA 之前思考一下，你是否認為這裡的機會是從 Tyvaso 轉變過來的，或者更多的是從 YUTREPIA 開始的新患者開始？ PAH 和 PH-ILD 之間有區別嗎？

I think it's largely a new patient start paradigm. I think what -- the way we view this is we want doctors to use it a few times, get comfortable with its use in a patients who is "de novo" to prostacyclin. And then once that comfort base exists, then potentially they would switch. But I think the real opportunity here is we see it is more in the de novo patient base. There's a lot of turnover here. As you know, patients -- this is an unrelenting disease, patients come on and come off the drug -- their drugs commonly over time.

我認為這很大程度上是一個新的患者啟動範例。我認為，我們對此的看法是，我們希望醫生使用它幾次，並在“從頭”使用前列環素的患者中適應它的使用。一旦這種舒適基礎存在，他們就有可能會改變。但我認為真正的機會是我們看到它更多地發生在新的患者基礎上。這裡的營業額很大。如您所知，患者 - 這是一種無情的疾病，患者開始服藥並停藥 - 他們的藥物通常會隨著時間的推移而變化。

So for us, it's more going after the de novo market, the market that's already on a process like and can be a little bit stickier. I think we had acknowledged that. So it's less about switches. Now having said that, I think if there's intolerance as we hear in particular with PH-ILD for Tyvaso and Tyvaso DPI for example that those patients, I think, would be readily accepting of a DPI formulation that perhaps may be more tolerable and more titratable.

因此，對我們來說，更多的是追求從頭市場，這個市場已經處於一個類似的過程，並且可能會更具粘性。我想我們已經承認了這一點。所以與開關無關。話雖如此，我認為，如果我們聽到特別是 PH-ILD 對 Tyvaso 和 Tyvaso DPI 存在不耐受，那麼我認為這些患者會很容易接受 DPI 製劑，這種製劑可能更耐受且更可滴定。

So -- it's not that we won't go after the switches, I think our initial push will be in the de novo patient market, which example, I would say, look, there's lots of patients treated, I think users reporting over 6,000 on therapy at this point, seems to be about a 50-50 split between the nebulized and DPI formulations roughly speaking.

所以，這並不是說我們不會追求這些轉變，我認為我們最初的推動將是在新的患者市場，我會說，看，有很多患者接受治療，我認為用戶報告超過 6,000在這一點上，粗略地說，霧化製劑和DPI 製劑之間的比例似乎約為50-50。

And I think the other opportunity here, I probably should have mentioned is once we establish the use and efficacy of YUTREPIA, for example, in PAH, we will then go after its prostacyclin of first choice because we think is probably a better option because it's gentler to take and is now readily titratable in the YUTREPIA format and could displace oral prostacyclins, including Orenitram and Uptravi.

我認為我可能應該提到的另一個機會是，一旦我們確定了YUTREPIA 的用途和功效，例如，在PAH 中，我們將首先選擇前列環素，因為我們認為這可能是一個更好的選擇，因為它YUTREPIA 服用更溫和，現在很容易滴定，可以取代口服前列環素，包括 Orenitram 和 Uptravi。

Operator, next question, please.

接線員，請下一個問題。

And our next question coming from the line out of Kambiz Yazdi with Jefferies.

我們的下一個問題來自 Kambiz Yazdi 與 Jefferies 的對話。

How should we think about OpEx moving forward with the YUTREPIA open-label study and then eventually the L606 Phase III?

我們應該如何看待 OpEx 繼續推進 YUTREPIA 開放標籤研究以及最終的 L606 III 期研究？

Yes, that's a great question. I'll ask our CFO, Mike Kaseta, please.

是的，這是一個很好的問題。我會請教我們的首席財務官 Mike Kaseta。

So as I said earlier, we ended Q2 with about $88 million in cash. We feel very confident in our ability to get through key events in 2024, which includes onboarding our extended sales force in Q4 of '23 when we get the green light to move ahead, we will -- to launch YUTREPIA, we will be ready to do that and hit the ground running on day 1.

正如我之前所說，我們在第二季度結束時擁有約 8800 萬美元的現金。我們對完成 2024 年重大事件的能力非常有信心，其中包括在 23 年第四季度加入我們的擴展銷售隊伍，當我們獲得前進的綠燈時，我們將推出 YUTREPIA，我們將準備好這樣做並在第一天就開始工作。

So very confident there. As it relates to L606, as I mentioned, we made a $10 million upfront payment to Pharmosa. We would expect that the vast majority of development expenses will happen as we do (technical difficulty) as the Phase III progresses. So in the end, we're very confident with where we are still a (technical difficulty) when given the clarity to do so.

所以非常有信心。正如我提到的，就 L606 而言，我們向 Pharmosa 支付了 1000 萬美元的預付款。我們預計隨著第三階段的進展，絕大多數開發費用將像我們一樣發生（技術困難）。因此，最後，當我們明確這樣做時，我們對我們仍然存在的（技術困難）非常有信心。

Operator, next question, please.

接線員，請下一個問題。

(Operator Instructions) And our next question coming from the line of Matthew Kaplan with Ladenburg.

（操作員說明）我們的下一個問題來自 Matthew Kaplan 和 Ladenburg 的線路。

I guess can you comment a little bit more on why you're confident in being successful at the CAFC in the United PTAB appeal.

我想您能否多評論一下為什麼您有信心在聯合 PTAB 上訴中在 CAFC 獲得成功。

Yes. Matt, could you repeat the question you broke up a little bit there.

是的。馬特，你能重複一下你剛才提出的問題嗎？

Yes. Can you comment a little bit more on why you're confident in being successful at the CAFC and the United PTAB appeal?

是的。您能否進一步評論一下為什麼您有信心在 CAFC 和 United PTAB 上訴中取得成功？

Sure. I think Rusty addressed some of that in his prepared remarks. But Rusty, if you would maybe emphasize some additional points if you could?

當然。我認為拉斯蒂在他準備好的發言中談到了其中的一些內容。但是 Rusty，如果可以的話，您能否強調一些額外的要點？

Sure. The standard -- Matt, has to do with the burden or the standard as to when the court appeals for the Federal Circuit will overturn decision of the PTAB. It typically is a situation where there's been clear error, especially where you're dealing mostly with factual findings of the PTAB as is the case here.

當然。 Matt 的標準與聯邦巡迴法院上訴何時推翻 PTAB 的決定的負擔或標準有關。這通常是存在明顯錯誤的情況，尤其是當您主要處理 PTAB 的事實調查結果時，就像這裡的情況一樣。

So again, it's looking at the specifics of the holding and sort of our view that the holding is sensible and supported by substantial evidence and then that high bar of what you would you know you have to show as clear error in order to overturn the lower court decision or the PTAB decision in this case.

所以，再次強調，我們正在考慮持有的具體情況，以及我們的觀點，即持有是合理的，並且有大量證據支持，然後你知道你必須表現出明顯的錯誤，才能推翻較低的標準。本案中的法院判決或PTAB 判決。

Okay. That's helpful. And then just going back to a follow-up on L606. Can you talk a little bit about the potential development time line there? And is manufacturing a great learning step to potential filing for approval?

好的。這很有幫助。然後回到 L606 的後續部分。您能談談那裡潛在的開發時間表嗎？製造是否是潛在申請批准的一個很好的學習步驟？

Yes, I'll ask Rajeev, our Chief Medical Officer, who's ever seen the development to address that question.

是的，我會問我們的首席醫療官 Rajeev，他見證了解決這個問題的進展。

So first and foremost, just to highlight, the L606 program has one current ongoing open-label study that's active in the United States with the inclusion of the following patients. These are P -- Group 1 PAH patients that are either naive to prostacyclins or they can be transitioned from inhaled Tyvaso either the DPI or nebulized as well as patients that have PH-ILD that can be transitioned from Tyvaso DPI or Tyvaso nebulizer, to open-label L606. That study is already recruiting, and we have patients that have already achieved up to 1 year of exposure.

因此，首先要強調的是，L606 項目目前正在進行一項開放標籤研究，該研究在美國活躍，其中包括以下患者。這些是P——第1 組PAH 患者，他們要么未曾接受過前列環素治療，要么可以從吸入Tyvaso 過渡到DPI 或霧化，以及患有PH-ILD 的患者，可以從Tyvaso DPI 或Tyvaso 霧化器過渡到開放式治療。 -標籤L606。該研究已經開始招募，我們的患者已經接受了長達一年的暴露。

The priority now based on our understanding is that we are going to be seeking a Type B discussion with the FDA that's first and foremost priority to just confirm that the requirement from our understanding is a single placebo-controlled study with L606, specifically in PH-ILD. We believe that, that study in particular, plus our Phase I study in that combination will be enough for -- to seek NDA approval for both indications of PAH and PH-ILD. Roger, back to you.

根據我們的理解，現在的首要任務是，我們將尋求與 FDA 進行 B 型討論，首要任務是確認我們理解的要求是針對 L606 的單一安慰劑對照研究，特別是在 PH- ILD。我們相信，特別是該研究，加上我們在該組合中的第一階段研究將足以尋求針對 PAH 和 PH-ILD 兩種適應症的 NDA 批准。羅傑，回到你身邊。

Yes. Thanks, Rajeev. And Matt, as the time line, we're a little bit silent. We want to get through the Type B meeting. Again, there's a good proxy for what we need to do just from the Tyvaso ILD study that was done. So there's precedent in terms of sample size, time to get that study enrolled. And I think given its PH-ILD and that will be sort of unencumbered by background therapies, I think it would be potentially faster than what you've seen previously, particularly if somebody was doing a PAH only study. So again, it will take us a few years, but I think we have the chance to become the first less than 4 times a day option for patients.

是的。謝謝，拉吉夫。馬特，隨著時間的推移，我們有點沉默。我們希望通過 B 類會議。同樣，從已完成的 Tyvaso ILD 研究中可以很好地看出我們需要做什麼。因此，在樣本量和註冊研究的時間方面都有先例。我認為考慮到 PH-ILD 並且不會受到背景治療的阻礙，我認為它可能會比你之前看到的更快，特別是如果有人只進行 PAH 研究的話。再說一次，我們需要幾年的時間，但我認為我們有機會成為患者第一個每天少於 4 次的選擇。

Operator, next question, please.

接線員，請下一個問題。

And I see no further questions in the Q&A queue at this time. I will now turn the call back over to you, Dr. Jeffs for any closing remarks.

目前我在問答隊列中沒有看到更多問題。傑夫斯博士，我現在將把電話轉回給您，請您發表結束語。

Thank you, operator. So with no further questions, again, I'd like to thank you for joining us today. And we look forward to reporting on our continued progress in the coming quarters. Goodbye.

謝謝你，接線員。沒有其他問題了，我再次感謝您今天加入我們。我們期待在未來幾個季度報告我們的持續進展。再見。

Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect.

女士們、先生們，今天的會議到此結束。感謝您的參與。您現在可以斷開連接。