Palvella Therapeutics Inc (PVLA) 2022 Q2 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Pieris Pharmaceuticals Second Quarter Earnings Call. I will now turn the program over to Tom Bures, Chief Financial Officer.

早安，女士們、先生們，歡迎參加 Pieris Pharmaceuticals 第二季財報電話會議。我現在將該計劃移交給財務長 Tom Bures。

Good morning, everyone, and thank you for joining us for our second quarter 2022 conference call and corporate update. On the call today, we have Steve Yoder, our President and CEO, who will provide a corporate overview and outlook on our pipeline; Hitto Kaufmann, our Chief Scientific Officer; and Shane Olwill, our Chief Development Officer, who will be available for Q&A.

大家早安，感謝您參加我們的 2022 年第二季電話會議和公司最新動態。在今天的電話會議上，我們的總裁兼執行長 Steve Yoder 將提供公司概況和對我們管道的展望； Hitto Kaufmann，我們的首席科學長；我們的首席開發長 Shane Olwill 將出席問答環節。

You can access the press release released this morning on the Investor Relations page of our website at www.pieris.com.

您可以在我們網站 www.pieris.com 的投資者關係頁面上造訪今天早上發布的新聞稿。

Before we begin, I'd like to caution that comments made during this conference call may contain forward-looking statements involving risks and uncertainties regarding the operations and future results of operations of Pieris, including statements related to the timing and progress of our clinical trials and preclinical programs, including the anticipated timing for reporting of data, our partnerships and our financial position, and actual results or events may differ materially from those expressed or implied by such forward-looking statements. Factors that might cause such differences are described in our filings with the SEC, including our annual, quarterly and current reports. The information being presented is only accurate as of today, and Pieris undertakes no obligation to update any statements to reflect future events or circumstances.

在我們開始之前，我想提醒大家，本次電話會議期間發表的評論可能包含涉及 Pieris 營運和未來營運結果的風險和不確定性的前瞻性陳述，包括與我們臨床試驗的時間和進度相關的陳述和臨床前計劃，包括數據報告的預期時間、我們的合作夥伴關係和我們的財務狀況以及實際結果或事件可能與此類前瞻性陳述明示或暗示的內容存在重大差異。我們向 SEC 提交的文件中描述了可能導致此類差異的因素，包括我們的年度報告、季度報告和當前報告。所提供的資訊僅截至今日準確，Pieris 不承擔更新任何聲明以反映未來事件或情況的義務。

With that, I will now turn the call over to Steve.

現在，我將把電話轉給史蒂夫。

Thank you, Tom, and thank you to everyone for joining us today for our second quarter 2022 earnings call. Before diving into the detailed updates from today's earnings release, I would like to acknowledge the tough economic climate, not least for small-cap biotech companies like Pieris. While we are excited about the high value potential of our programs and their continued advancement, along with the fact that we have several committed alliance partners to help advance this pipeline, we have not been spared the tough decision-making that goes along with being a resource-constrained company in this market environment. The challenges of drug development require the need to focus, which is our guiding principle as we continue to prioritize our lead respiratory program, PRS-060 or AZD1402. These themes will be reflected during today's call as we cover an update of our pipeline, the outlook over the coming quarters and the ability of our balance sheet and cost-effective program structures to deliver on our goals.

謝謝湯姆，也謝謝大家今天參加我們的 2022 年第二季財報電話會議。在深入了解今天財報的詳細更新之前，我想承認經濟狀況嚴峻，尤其是像 Pieris 這樣的小型生技公司。雖然我們對我們的計劃的高價值潛力及其持續進步感到興奮，而且我們有幾個忠誠的聯盟合作夥伴來幫助推進這一管道，但我們也未能倖免於作為一個在這種市場環境下，公司資源有限。藥物開發的挑戰需要集中精力，這是我們繼續優先考慮我們的主要呼吸系統項目 PRS-060 或 AZD1402 的指導原則。這些主題將在今天的電話會議中反映，我們將討論我們的管道更新、未來幾季的前景以及我們的資產負債表和具有成本效益的計劃結構實現我們目標的能力。

Turning to our pipeline. I would first like to give an update on our lead respiratory program, which I just mentioned, PRS-060 or AZD1402 in inhaled IL-4 receptor alpha inhibitor that we are developing with AstraZeneca for the treatment of moderate to severe asthma. AstraZeneca is conducting a Phase IIa study with a dry powder formulation. Having successfully completed the safety portion of the 1 milligram and 3-milligram cohorts in moderate asthmatics controlled on standard of care last year, AstraZeneca is currently enrolling the 1 milligram and 3-milligram efficacy dose cohorts. In this part of the study, PRS-060 is being administered twice a day on top of standard of care regimen in moderate uncontrolled asthmatic patients randomized across 2 doses and 1 placebo arm. Additionally, AstraZeneca is currently enrolling the 10-milligram safety portion of the Phase IIa study, randomized between treatment to placebo.

轉向我們的管道。我首先想介紹我們的主要呼吸計畫的最新情況，我剛才提到了我們正在與阿斯特捷利康合作開發的吸入性IL-4 受體α 抑制劑中的PRS-060 或AZD1402，用於治療中度至重度氣喘。阿斯特捷利康正在進行乾粉製劑的 IIa 期研究。阿斯特捷利康去年成功完成了在標準護理控制下的中度氣喘患者中的 1 毫克和 3 毫克隊列的安全部分，目前正在招募 1 毫克和 3 毫克有效劑量隊列。在這部分研究中，在標準護理方案的基礎上，PRS-060 每天兩次被隨機分配到 2 個劑量組和 1 個安慰劑組的中度未受控制的氣喘患者。此外，阿斯特捷利康目前正在招募 IIa 期研究的 10 毫克安全部分，隨機分配治療組和安慰劑組。

In last quarter's earnings update, we communicated there was a heightened risk of a delay in the availability of top line results from the Phase IIa study, given geopolitical and pandemic-driven challenges. We are now guiding that following a time line reforecast by AstraZeneca, accounting for the challenges of recruiting for respiratory clinical trials caused by the continued impact of COVID-19, the top line results for the Phase IIa study are now expected to be reported by the third quarter of 2023. This updated time line follows a significant amount of analysis and is informed by 2 important updates to the study, which I will now explain in more detail.

在上季的收益更新中，我們表示，鑑於地緣政治和大流行病驅動的挑戰，IIa 期研究的頂線結果延遲提供的風險加大。我們現在指導，在阿斯特捷利康重新預測時間線後，考慮到因 COVID-19 的持續影響而導致的呼吸系統臨床試驗招募的挑戰，IIa 期研究的主要結果現在預計將由2023 年第三季度。這個更新的時間表遵循了大量的分析，並根據研究的2 個重要更新提供信息，我現在將更詳細地解釋這些更新。

First, AstraZeneca is simplifying the protocol to relieve site burden and increase recruitment rates. This includes changes such as broadening ICS or LABA, the standard of care combination and allowing separate devices, modifying FEV1 criteria and broadening exacerbation criteria, to cite a few examples. Second, AstraZeneca will be focusing the efficacy phase on the 3-milligram dose, which is anticipated to be a dose that represents an optimal composite of efficacy and commercial attractiveness based on data from prior studies and the modeling of the 3-milligram dose as well as CMC considerations. In connection with the aforementioned trial amendments intended to boost enrollment rates, AstraZeneca will then cease enrollment of the 1 milligram cohort and will no longer be enrolling a 10-milligram efficacy cohort. AZ remains committed to completing enrollment of the ongoing 10-milligram safety cohort.

首先，阿斯特捷利康正在簡化方案以減輕現場負擔並提高招募率。舉幾個例子，這包括擴大 ICS 或 LABA、護理組合標準和允許單獨的設備、修改 FEV1 標準和擴大惡化標準等變化。其次，阿斯特捷利康將把功效階段的重點放在 3 毫克劑量上，根據先前研究的數據和 3 毫克劑量的建模，預計該劑量將代表功效和商業吸引力的最佳組合。作為CMC 的考慮因素。與上述旨在提高入組率的試驗修正案相關，阿斯特捷利康將停止 1 毫克療效隊列的入組，並且將不再入組 10 毫克功效組。 AZ 仍致力於完成正在進行的 10 毫克安全隊列的註冊。

Accordingly, the top line results to be reported next year will include the safety data for all 3 dose cohorts, that is the 1 milligram, 3 milligram, which have both passed the safety gate, and the 10 milligram, which is ongoing. The efficacy data from the 3-milligram cohort, which we continue to believe is appropriately powered versus placebo for a proof-of-concept study assessing FEV1 improvement and some limited efficacy data from the 1 milligram cohort, given that patients will continue to be randomized into the 1 milligram cohort until the aforementioned protocol amendments become active. We believe that these study design updates will allow AstraZeneca to run a more focused and efficient study without compromising on what we believe is the key cohort of the study in which we think will ensure a well-informed co-development opt-in decision following review of the Phase IIa data next year.

因此，明年報告的主要結果將包括所有 3 個劑量組的安全性數據，即 1 毫克、3 毫克（均已通過安全門）和 10 毫克（正在進行中）。 3 毫克隊列的療效數據，我們仍然認為，對於評估FEV1 改善的概念驗證研究，與安慰劑相比，3 毫克隊列的療效數據是適當的；考慮到患者將繼續隨機分組，來自1 毫克隊列的一些有限療效數據進入 1 毫克隊列，直到上述方案修正案生效。我們相信，這些研究設計的更新將使阿斯特捷利康能夠進行一項更有針對性和更有效率的研究，而不會影響我們認為研究的關鍵群體，我們認為這將確保在審查後做出明智的共同開發選擇決定明年的IIa期資料。

Beyond PRS-060, we continue to work on 2 discovery-stage programs with AstraZeneca for which we recently extended our research term. We retained co-development and U.S. co-commercialization options for each of these 2 programs. Beyond our partnered respiratory pipeline, we are making high-impact investments on a focused set of proprietary assets. Our most advanced proprietary asset is PRS-220, a proprietary inhaled Anticalin protein targeted connective tissue growth factor, or CTGF, for the treatment of idiopathic pulmonary fibrosis, which continues to move forward according to plan. I'm pleased to report that a regulatory filing seeking authorization for a first-in-human clinical study has been submitted. Pending approval, we expect PRS-220 will enter a Phase I study in healthy volunteers as an oral inhaled nebulized formulation later this year with the study outcome anticipated next year.

除了 PRS-060 之外，我們還繼續與阿斯特捷利康合作 2 個發現階段項目，最近我們延長了研究期限。我們為這兩個項目保留了共同開發和美國共同商業化的選項。除了我們合作的呼吸管道之外，我們還對一組集中的專有資產進行高影響力的投資。我們最先進的專有資產是PRS-220，這是一種專有的吸入性Anticalin 蛋白靶向結締組織生長因子（CTGF），用於治療特發性肺纖維化，該計畫繼續按計劃向前推進。我很高興地報告，尋求首次人體臨床研究授權的監管文件已經提交。在等待批准期間，我們預計 PRS-220 將在今年稍後作為口服吸入霧化製劑在健康志願者中進入 I 期研究，並預計明年得出研究結果。

I would now like to give a brief update on our IO pipeline, beginning with what has been our flagship 4-1BB bispecific program for several years, which is our 4-1BB/HER2 bispecific PRS-343 cinrebafusp alfa or CINRA for short, which has been in a Phase II study for both HER2 high and separately HER2-low gastric cancer.

現在我想簡單介紹一下我們的 IO 管道，首先是我們多年來的旗艦 4-1BB 雙特異性計劃，即我們的 4-1BB/HER2 雙特異性 PRS-343 cinrebafusp alfa 或簡稱 CINRA，它已進行HER2高胃癌和HER2 低胃癌的II 期研究。

As a reminder, in a Phase I escalation study, CINRA had shown clear single-agent activity especially demonstrating meaningful activity in HER2-expressing gastric cancer patients. We believe the publicly disclosed clinical data from CINRA revalidated 4-1BB as a clinical intervention point, leading to several additional third-party approaches to localized 4-1BB agonism. Despite the progress we have made on this program since it entered clinical development as the first clinical stage 4-1BB bispecific, we have made a strategic pipeline decision to cease enrollment of this program in order to focus our resources, and we are now conducting an orderly wind down of this program. Although we will no longer be advancing this program towards approval, the clinical data we have generated with CINRA have been of great value, giving both Pieris and its partners conviction in our 4-1BB-based bispecific franchise more broadly. I want to sincerely thank the team who has worked tirelessly on bringing CINRA forward to the patients that have participated in our trials and to the investigators who have worked with us on the clinical development of this drug candidate.

提醒一下，在 I 期升級研究中，CINRA 顯示出明顯的單藥活性，尤其是在表達 HER2 的胃癌患者中表現出有意義的活性。我們相信，CINRA 公開揭露的臨床數據重新驗證了 4-1BB 作為臨床幹預點的有效性，從而催生了幾種額外的第三方局部 4-1BB 激動方法。儘管自從該計畫作為第一個臨床階段4-1BB 雙特異性藥物進入臨床開發以來我們已經取得了進展，但我們已做出策略性管道決定，停止該計畫的招募，以集中我們的資源，我們現在正在進行一項該計劃有序結束。儘管我們將不再推進該專案的批准，但我們與 CINRA 產生的臨床數據具有巨大的價值，使 Pieris 及其合作夥伴對我們基於 4-1BB 的雙特異性特許經營權更加廣泛地充滿信心。我要衷心感謝為將 CINRA 帶給參與我們試驗的患者以及與我們合作進行該候選藥物臨床開發的研究人員而不懈努力的團隊。

Speaking of our broader 41BB franchise, we continue to enroll the Phase I/II study of PRS-344, also known as S-09-5012, which is a 4-1BB/PD-L1 Anticalin-based bispecific for the treatment of solid tumors that we are developing in collaboration with Servier. We expect to have data from the study to inform expansion on a select number of jointly vetted indications by year-end. We continue to believe this program has the potential to drive clinical benefit, and we are narrowing in on what indications we would like to pursue. Indication selection criteria include an efficient development approach, combining the high probability of success to both proof-of-concept and BLA filing, along with the consideration for biology, regulatory path and financial considerations. As a reminder, we retained full U.S. rights for this program, and we receive royalties on any ex U.S. sales by Servier. Beyond PRS-344, Servier is also continuing the development of PRS-352 or S-09-5025, an OX40 PD-L1 bispecific.

說到我們更廣泛的41BB 特許經營權，我們繼續開展PRS-344（也稱為S-09-5012）的I/II 期研究，這是一種基於4-1BB/PD-L1 Anticalin 的雙特異性藥物，用於治療實體腫瘤我們正在與施維雅合作開發腫瘤。我們期望在年底前獲得該研究的數據，為擴大選定數量的聯合審查適應症提供資訊。我們仍然相信該計劃有潛力推動臨床效益，並且我們正在縮小我們想要追求的適應症。適應症選擇標準包括高效的開發方法，將概念驗證和 BLA 備案的高成功機率結合起來，同時考慮生物學、監管路徑和財務因素。提醒一下，我們保留了該計劃在美國的全部權利，並且我們從施維雅在美國之前的任何銷售中收取特許權使用費。除了 PRS-344 之外，施維雅也持續開發 PRS-352 或 S-09-5025（一種 OX40 PD-L1 雙特異性抗體）。

I would like to quickly end on a brief update on some of our other collaborations with other programs within our oncology franchise. First, Boston Pharmaceuticals continues to advance PRS-342, or BOS 342, a 4-1BB GPC3 bispecific towards the clinic. We expect Phase 1 to begin in the first half of 2023, which would trigger a milestone payment. Additionally, Seagen continues to make great progress advancing the first program within our alliance which is an undisclosed costimulatory bispecific. We are pleased with the progress of the program for which we hope to share additional details later this year. Seagen also continues the development of a second program in the collaboration, and we retain a co-promotion option in the United States for one of the programs in the alliance. Beyond oncology, Genentech discovery-stage collaboration we initiated last year continues to be a source of excitement for us, further bolstering our respiratory pipeline while investigating a new application for our technology in ophthalmology in addition to additional platform investments.

最後，我想簡要介紹一下我們與腫瘤學專營權內其他項目的一些其他合作。首先，波士頓製藥公司持續將 PRS-342 或 BOS 342（一種 4-1BB GPC3 雙特異性藥物）推向臨床。我們預計第一階段將於 2023 年上半年開始，這將觸發里程碑付款。此外，Seagen 在推進我們聯盟內的第一個項目方面繼續取得巨大進展，該項目是一個未公開的共刺激雙特異性項目。我們對該計劃的進展感到高興，我們希望在今年稍後分享更多細節。 Seagen 也繼續開發合作中的第二個項目，並且我們為聯盟中的其中一個項目保留了在美國共同推廣的選項。除了腫瘤學之外，我們去年發起的基因泰克發現階段合作仍然讓我們興奮不已，除了額外的平台投資之外，還進一步增強了我們的呼吸產品線，同時研究了我們的技術在眼科領域的新應用。

As a final update, I would like to mention that Dr. Tim Demuth, who has served as Senior Vice President and Chief Medical Officer, will be leaving the company, and I would like to thank Tim for his contributions to Pieris and to wish him all the best in his future endeavors. As we stay focused on PRS-060, partnered with AstraZeneca, PRS-344, partnered with Servier, and PRS 220, which will soon enter a Phase I study in healthy volunteers, we're fortunate to have a great stable of partners to complement a solid talent base at Pieris to advance several programs through multiple clinical readouts within the next 12 months.

作為最後的更新，我想提一下，曾擔任高級副總裁兼首席醫療官的 Tim Demuth 博士將離開公司，我要感謝 Tim 對 Pieris 的貢獻並祝愿他他未來的努力一切順利。由於我們繼續專注於與阿斯特捷利康合作的PRS-060、與施維雅合作的PRS-344 以及即將在健康志願者中進入I 期研究的PRS 220，我們很幸運能夠擁有一大批穩定的合作夥伴來補充Pieris 擁有堅實的人才基礎，可在未來 12 個月內透過多次臨床試驗推進多個計畫。

This concludes my prepared remarks, and I would now like to hand the call over to Tom.

我準備好的演講到此結束，現在我想將電話轉交給湯姆。

Thank you, Steve, and good morning again, everyone. Before providing an update on our quarterly financial results, I wanted to reiterate our commitment to managing our balance sheet to deliver important program updates in the coming months. With the wind down of CINRA Phase II trials, along with the expectation of modest near-term development milestones across a number of programs, the company now believes operations are sufficiently funded into the second quarter of 2024.

謝謝你，史蒂夫，大家早安。在提供季度財務業績的最新資訊之前，我想重申我們對管理資產負債表的承諾，以便在未來幾個月內提供重要的計劃更新。隨著 CINRA 二期試驗的結束，以及多個項目近期將取得適度發展里程碑的預期，該公司現在認為，營運資金充足，可以持續到 2024 年第二季。

Cash and cash equivalents totaled $80.9 million for the quarter ended June 30, 2022, compared to a cash and cash equivalents balance of $117.8 million for the quarter ended December 31, 2021. This decrease is due to funding operations in the first half of 2022. Our R&D expenses were $11.9 million for the quarter ended June 30, 2022, compared to $15.8 million for the quarter ended June 30, 2021. This decrease is due to lower program costs as work related to the company's sponsored Phase I trial of PRS-060 was largely complete in 2021 as well as lower manufacturing costs across all later stage respiratory and immuno-oncology programs, lower collaboration license fees due to new partnerships entered into in 2021 and lower consulting costs. These lower costs were partially offset by higher clinical costs for PRS-344 partnered with Servier and higher manufacturing and preclinical costs for earlier-stage programs and finally, an increase in personnel costs.

截至2022 年6 月30 日的季度現金和現金等價物總額為8090 萬美元，而截至2021 年12 月31 日的季度現金和現金等價物餘額為1.178 億美元。這一減少是由於2022 年上半年的融資業務所致。截至2022 年6 月30 日的季度，我們的研發費用為1,190 萬美元，而截至2021 年6 月30 日的季度為1,580 萬美元。這一下降是由於與公司贊助的PRS-060第一階段試驗相關的工作導致項目成本降低。2021 年基本完成，所有後期呼吸系統和免疫腫瘤學項目的製造成本降低，由於2021 年建立新的合作夥伴關係而降低了合作許可費用，並且諮詢成本也降低了。這些較低的成本被與施維雅合作的 PRS-344 較高的臨床成本、早期項目較高的製造和臨床前成本以及最後人員成本的增加部分抵消。

Our G&A expenses were $4.1 million for the quarter ended June 30, 2022, compared to $4.2 million for the quarter ended June 30, 2021. This period-over-period decrease was driven primarily by lower professional service costs and lower facility costs, partially offset by the return of some travel expenses. For the quarter ended June 30, 2022, we recorded $1.2 million of grant income for PRS-220 compared to $800,000 for the quarter ended June 30, 2021. This increase is due to higher levels of activity as the company plans to initiate a Phase I clinical trial for PRS-220 this year. And finally, our net loss was $10.3 million or a loss of $0.14 per share for the quarter ended June 30, 2022, compared to a net loss of $15.5 million or a $0.25 loss per share for the quarter ended June 30, 2021.

截至2022 年6 月30 日的季度，我們的一般管理費用為410 萬美元，而截至2021 年6 月30 日的季度為420 萬美元。這一同比下降主要是由於專業服務成本和設施成本下降，部分抵消了透過返還一些差旅費。截至2022 年6 月30 日的季度，我們記錄了PRS-220 的贈款收入120 萬美元，而截至2021 年6 月30 日的季度為80 萬美元。這一增長是由於公司計劃啟動第一階段的活動量較高今年PRS-220的臨床試驗。最後，截至2022 年6 月30 日的季度，我們的淨虧損為1,030 萬美元，即每股虧損0.14 美元，而截至2021 年6 月30 日的季度，我們的淨虧損為1,550 萬美元，即每股虧損0.25 美元。

And with that, I will turn the call back over to Stephen.

然後，我會將電話轉回給史蒂芬。

Well, thank you, Tom, and thank you for -- all of you for joining us today. We would now like to open the call for your questions.

好吧，謝謝你，湯姆，也謝謝你們所有人今天加入我們。我們現在想開始電話詢問您的問題。

(Operator Instructions) It looks like our first will come from Roger Song of Jefferies.

（操作員說明）看起來我們的第一個將來自 Jefferies 的 Roger Song。

The first one is for 060. So as AstraZeneca is reevaluating the enrollment and the study design, what kind of data they have been seeing along the process and to help them to make the decision 3-milligram may be optimal for the efficacy readout?

第一個是針對060 的。那麼當阿斯特捷利康正在重新評估招募和研究設計時，他們在整個過程中看到了什麼樣的數據並幫助他們做出決定，3 毫克可能是功效讀數的最佳選擇？

Sure. Thanks, Roger. So your question is what data are AZ using and maybe in totality to inform our view that the 3-milligram dose is the optimal dose to focus on for the efficacy trial portion, correct?

當然。謝謝，羅傑。所以你的問題是 AZ 使用哪些數據，也許全部數據都可以告訴我們這樣的觀點：3 毫克劑量是功效試驗部分的最佳劑量，對嗎？

Yes, that's right. Yes.

恩，那就對了。是的。

Yes. So I would point to maybe 2 groups of data here. As a reminder, this is a blinded study. And the efficacy portion 4, what we call Part IIa, which is the 1 milligram and the 3-milligram -- those are -- that's ongoing. So there would be no data from the efficacy part of the study to be used. But the first bucket of data that I would suggest they are using is just to make sure that the dose is safe, and we have that from the 1 and 3-milligram part -- Part 1a, which successfully passed the safety gate as we announced previously. And so that gives us great confidence of the safety of the drug. And then looking at a composite of other factors, which include the Phase Ib data, where we have nebulized administration in the pheno high population, and we could see a lot of good target engagement with the PD correlates looking at, in particular, pheno reductions relative to placebo over 10 days. We also know the correlation from PK and other preclinical modeling assessments on what nebulized data are dosing from Part 1b, what that correlates in terms of dry powder. And I think previously, we said that is roughly a 2:1 basis. So what is 3 milligrams in the dry powder is equivalent to 6 milligrams in the nebulized formulation. And we're very confident on the basis of the data we've seen in the Phase Ib that, that is an appropriate dose to be focusing on. There are a number of other preclinical data sets for modeling preclinical data that we also have used to collectively inform the view. And those are data sets that I would imagine will continue to be -- will be further if they're not publicly disclosed in due course so that everyone understands the rationale. But I would say, primarily, it is the pheno data which we think are the most positive in the decision to focus on the 3-milligram dose.

是的。所以我想在這裡指出可能有兩組數據。提醒一下，這是一項盲法研究。功效部分 4，我們稱之為第 IIa 部分，即 1 毫克和 3 毫克——這些是——正在進行中。因此，不會使用該研究的功效部分的數據。但我建議他們使用的第一桶數據只是為了確保劑量是安全的，我們從 1 毫克和 3 毫克部分（第 1a 部分）中獲得了這些數據，正如我們宣布的那樣，該部分成功通過了安全門之前。這讓我們對藥物的安全性充滿信心。然後綜合考慮其他因素，其中包括 Ib 期數據，我們在表型高人群中進行了霧化給藥，我們可以看到許多良好的目標參與與 PD 相關，特別是表型減少相對於安慰劑超過10天。我們也知道 PK 和其他臨床前模型評估中關於第 1b 部分中霧化資料劑量的相關性，以及與乾粉的相關性。我想之前我們說過這大約是 2:1 的基礎。因此，乾粉中的 3 毫克相當於霧化製劑中的 6 毫克。根據我們在 Ib 期中看到的數據，我們非常有信心，這是值得關注的適當劑量。還有許多其他用於對臨床前數據進行建模的臨床前數據集，我們也使用它們共同為視圖提供資訊。我認為這些數據集將繼續存在——如果它們沒有在適當的時候公開披露，以便每個人都理解其基本原理，那麼它們將會進一步存在。但我想說，我們認為主要是表型數據對於決定關注 3 毫克劑量是最積極的。

Excellent. All right. And the next one, also related to the 060. Can you just remind us what will be the sample size or patient side for 3-milligram for efficacy? Given this change for the design, would you increase the size to see better power? And second part of the question is what will be the potential next step after you read out the top line for 3 milligrams for efficacy? Will you go right into the pivotal? Or you will need to do additional study to explore kind of more doses if you see kind of very different results than you desire?

出色的。好的。下一個也與 060 有關。您能否提醒我們 3 毫克的療效的樣本量或患者側是多少？鑑於設計的這種變化，您會增加尺寸以獲得更好的功率嗎？問題的第二部分是，在您讀出 3 毫克的功效頂線後，下一步可能會是什麼？你會直接進入關鍵嗎？或者，如果您看到的結果與您想要的結果非常不同，您將需要進行額外的研究來探索更多的劑量？

Okay. So great, Roger. Those are -- so 2 questions in general there. I'm hearing. The first one concerns the power of the study, in particular, of the 3-milligram dose, how we're thinking about that in view of these modifications. And number two, what happens after the Phase IIa data, assuming the top line data are positive on FEV1 in totality.

好的。太棒了，羅傑。這些是——一般來說有兩個問題。我聽到了。第一個問題涉及研究的功效，特別是 3 毫克劑量，以及我們如何考慮這些修改。第二，假設 FEV1 總體數據為正，則 IIa 期數據之後會發生什麼。

So backing up to say, when we designed the study with AstraZeneca and AstraZeneca designed the study, there was a great deal of assessment that included the wealth of information we have from other IL-4 receptor alpha interventions, including dupilumab. So based on the totality of the data there based on other data that are proprietary to AstraZeneca, there is a great deal of confidence that the powering of the study to achieve the targeted FEV1 improvement endpoints is very appropriate, very robust for a Phase II proof-of-concept study. And that included roughly 80 patients in the placebo arm and then 80 patients in the treatment cohorts. So as it stands, we are maintaining the size of the placebo group and the size of the 3-milligram group. So that would be 80 patients in placebo and 80 patients in 3 milligrams. We think that is very well powered to look at the targeted endpoint of FEV1 improvement relative to placebo. There will be far fewer in the 1 milligram dose, as we mentioned, but the focus is clearly 3 milligrams. And so we feel very good about that. So as a result, we do not anticipate increasing size of any of the other cohorts or the placebo or the treatment. We think we're well placed there.

所以說，當我們與阿斯特捷利康一起設計這項研究時，阿斯特捷利康設計了這項研究，進行了大量的評估，其中包括我們從其他IL-4 受體α 幹預措施（包括dupilumab）獲得的大量資訊。因此，根據阿斯特捷利康專有的其他數據的整體數據，我們非常有信心地認為，該研究為實現目標 FEV1 改善終點的動力是非常合適的，對於第二階段的證明來說非常穩健概念研究。其中包括安慰劑組中的約 80 名患者，以及治療組中的 80 名患者。因此，我們維持安慰劑組和 3 毫克組的規模。因此，80 名患者服用安慰劑，80 名患者服用 3 毫克。我們認為這非常有利於研究相對於安慰劑的 FEV1 改善的目標終點。正如我們所提到的，1毫克劑量的含量會少得多，但重點顯然是3毫克。所以我們對此感覺非常好。因此，我們預計任何其他隊列或安慰劑或治療的規模都不會增加。我們認為我們在那裡處於有利地位。

And the interest is also to finely recruit the trial. And with COVID and with masking, as we talked about in prior calls, that has made it more challenging in general for any company to enroll any asthma trial at the current time. So I think we feel really good about all that.

且息亦精招試。正如我們在之前的電話會議中所討論的那樣，隨著新冠肺炎和掩蓋，這使得任何公司目前參加任何哮喘試驗都變得更具挑戰性。所以我認為我們對此感覺非常好。

Then with respect to next steps, I mean this is up to AstraZeneca, and it's part strategy, and it's going to be part data. We think either is possible. Phase IIb is probably more probable than straight to Phase III since a likely Phase III would have as an endpoint exacerbations over a 12-month period, which is different than the currently assessed endpoint of FEV1 over improvement at 4 weeks. I would remind you and everyone that importantly, as part of the co-development framework, AstraZeneca would need to deliver a plan and a budget through BLA which we will be able to communicate at the appropriate time and level of detail publicly before triggering any co-development option given the materiality there. So analysts, investors, any external stakeholders will clearly understand what the go-forward plan would be before we would trigger our co-development option. Is that clear?

然後關於下一步，我的意思是這取決於阿斯特捷利康，它部分是戰略，部分是數據。我們認為兩者都有可能。 IIb 期可能比直接進入 III 期更有可能，因為可能的 III 期將在 12 個月內以惡化為終點，這​​與目前評估的 FEV1 在 4 週內改善的終點不同。我想提醒您和大家，重要的是，作為共同開發框架的一部分，阿斯特捷利康需要通過 BLA 提供計劃和預算，我們將能夠在適當的時間和詳細程度公開溝通，然後再觸發任何合作。- 考慮到那裡的重要性，開發選項。因此，在我們觸發共同開發選項之前，分析師、投資者和任何外部利害關係人都會清楚了解未來計劃是什麼。明白了嗎？

No, that's very, very, very helpful. I think it's clear. Okay. So that's for 060. Maybe just one question for your IO program in general. Maybe since you mentioned the data from 4343 CINRA data from both Phase I and the Phase II, you see the clinical benefit. Can you just elaborate on what kind of clinical benefit you see in the Phase IIa, which you just kind of reduced enrollment? And is that consistent with what you have been seeing in the Phase I? And also, what gives you the confidence your 4-1BB program will still generate the benefit in other ongoing trials?

不，這非常非常非常有幫助。我想很清楚了。好的。這就是 060 的問題。也許只是您的 IO 程式的一個問題。也許自從您提到了 I 期和 II 期的 4343 個 CINRA 數據中的數據後，您就看到了臨床益處。您能否詳細說明您在 IIa 期試驗中看到了什麼樣的臨床益處，您只是減少了入組人數？這與您在第一階段看到的情況一致嗎？此外，是什麼讓您有信心您的 4-1BB 計劃仍能在其他正在進行的試驗中產生效益？

Sure. Okay. Yes. Great questions. So starting with the ongoing Phase II study, the data we're seeing is, we think, very consistent with what we observed and published in the Phase I study, which included a number of gastric cancer patients, including patients that had progressed after receiving immunotherapy, checkpoint therapy, the KEYNOTE-11 regimen and then had a meaningful and durable benefit even on monotherapy when receiving CINRA. So yes, we -- in this ongoing study, which we're winding down now, we did see responses that suggests the drug is active and provides clinical benefit to patients. We did enroll a limited number of patients, so we don't want to over-interpret the data as it relates to the 343 itself. But the clinical data observed gives us confidence in the localized 4-1BB agonism approach generally. And that leads into your second question. What we know from CINRA, it's safe, it's well tolerated, has a very manageable low immunogenicity profile. And monotherapy and combo, it's safe and well tolerated. It's very active. And it is relevant over standard of care, including checkpoint therapies. The open hypothesis is durability. And we need more time. And we simply didn't have enough time to test that hypothesis given the totality of our other pipeline members, the balance sheet and the current economic environment. So this is not based on any negative data. This is based on the current economic landscape. And we trust that our partners actually see it the same way. CINRA was a major positive for 4-1BB, as I mentioned, it put 4-1BB back on the map, and we're proud of that.

當然。好的。是的。很好的問題。因此，從正在進行的 II 期研究開始，我們認為，我們看到的數據與我們在 I 期研究中觀察到和發表的數據非常一致，其中包括一些胃癌患者，包括接受治療後病情進展的患者免疫療法、檢查點療法、KEYNOTE-11 療法，然後在接受CINRA 時即使單一療法也能產生有意義且持久的益處。所以，是的，我們——在這項正在進行的研究中，我們現在正在結束這項研究，我們確實看到了表明該藥物具有活性並為患者提供臨床益處的反應。我們確實招募了有限數量的患者，因此我們不想過度解釋數據，因為它與 343 本身相關。但觀察到的臨床數據總體上讓我們對局部 4-1BB 激動方法充滿信心。這就引出了你的第二個問題。我們從 CINRA 了解到，它是安全的、耐受性良好、具有非常易於管理的低免疫原性特徵。單一療法和聯合療法都是安全且耐受性良好的。它非常活躍。它與護理標準相關，包括檢查點療法。開放的假設是耐久性。我們需要更多時間。考慮到我們其他管道成員的整體情況、資產負債表和當前的經濟環境，我們根本沒有足夠的時間來檢驗這個假設。所以這並不是基於任何負面數據。這是基於當前的經濟狀況。我們相信我們的合作夥伴實際上也有同樣的看法。 CINRA 對 4-1BB 來說是一個重大的積極因素，正如我所提到的，它使 4-1BB 重新回到地圖上，我們為此感到自豪。

The next person in queue will be Jonathan Miller of Evercore ISI.

隊列中的下一個人將是 Evercore ISI 的喬納森·米勒 (Jonathan Miller)。

I think let's start with Pieris-060. It feels like the delay here is longer than most folks were expecting even though we knew there was going to be some sort of recalculation here. So could you maybe give us a little bit more color on whether this is just enrollment? You mentioned a couple of changes to trial design, which -- all of which seem to be indicating a faster enrollment or at least an attempt to accelerate enrollment. So can you try and square that circle for us given that you're dropping 10-milligram efficacy, you're dropping 1 milligram efficacy down to a much lower enrollment. How is -- why is it that the delay is so substantial in the program?

我想讓我們從 Pieris-060 開始。儘管我們知道這裡將會進行某種重新計算，但感覺這裡的延遲比大多數人預期的要長。那麼您能否給我們更多的資訊來說明這是否只是註冊？您提到了試驗設計的一些變化，所有這些似乎都表明註冊速度更快，或至少嘗試加速註冊。那麼，考慮到您要降低 10 毫克功效，您可以嘗試為我們解決這個問題嗎？您可以將 1 毫克功效降低到更低的註冊人數。為什麼該計劃的延遲如此之大？

Great question, John. Thanks for the candid question. Look, I can say, based on everything that we're seeing, on the ground with AZ, the project team, the leadership at AZ. This is still a very high priority project. And you may say, well, why are the time lines third quarter if we are making, in fact, not just amendments to boost enrollment rates, but also skinny-ing down the trial to what we think is still the bull's eye? It is not the same world as it was 3 years ago, simply put. The impact of COVID is immense for respiratory trials. And I don't think everyone's fully appreciated that. It's temporal, but it's happening right now. And that is not just the supply chain, the human capital element of finding focused sites and CROs to manage it. It's also the masking. The masking has, in fact, changed the disease control [temporally], and that is impacting the enrollment rates. So we think that based on what I would characterize as a very thorough and accurate and pragmatic assessment that with all these changes, AZ is going to deliver the trial, and it's going to deliver the trial in the essential piece, which is the 3-milligram dose. So we feel good about the time lines we feel good about the changes, and we're just going to have to wait for the data now. And as that is our priority program, we made these other difficult decisions to make sure that we're adequately capitalized to do that while making other high-impact investments on other programs like 220 and like 344. But I don't wake up in the morning and wonder if AZ's committed to this program. I think they're acting very resourcefully and entrepreneurial, and I commend them for their efforts.

好問題，約翰。感謝您的坦誠提問。我可以說，根據我們在 AZ、專案團隊和 AZ 領導層所看到的一切。這仍然是一個非常高度優先的項目。你可能會說，好吧，如果我們實際上不僅要進行修改以提高入學率，而且還要將試驗縮減到我們認為仍然是靶心的程度，那為什麼要在第三季度呢？簡言之，現在的世界與三年前已經不一樣了。新冠肺炎對呼吸系統試驗的影響是巨大的。我認為並不是每個人都充分意識到這一點。這是暫時的，但它現在正在發生。這不僅是供應鏈，還包括尋找重點地點和 CRO 來管理供應鏈的人力資本要素。這也是掩蔽。事實上，掩蓋[暫時]改變了疾病控制，這正在影響入學率。因此，我們認為，基於我所描述的非常徹底、準確和務實的評估，透過所有這些變化，AZ 將提供試驗，並將提供關鍵部分的試驗，即 3-毫克劑量。因此，我們對時間軸感覺良好，我們對這些變化感覺良好，我們現在只需要等待數據。由於這是我們的優先計劃，我們做出了這些其他艱難的決定，以確保我們有足夠的資本來做到這一點，同時對 220 和 344 等其他計劃進行其他高影響力的投資。早上想知道AZ 是否致力於該計劃。我認為他們的表現非常足智多謀、富有創業精神，我對他們的努力表示讚賞。

I think then maybe following up on that, does this delay and your need to reprioritize and conserve money change your calculus around the various opt-in levels? Are you still expecting to at least do that 25% opt-in?

我想接下來，這種延遲以及您重新確定優先順序和節省資金的需要是否會改變您對各種選擇加入等級的計算？您是否仍期望至少有 25% 的人選擇加入？

Yes. I'll tee that up at a high level, and I'll let Tom provide a little more color. I think the way we have negotiated several years ago, the co-development structure; number one, it's very affordable even in the current environment at the 25%. And number two, because of the overall risk-reward benefit from what we know about the intervention of this pathway, how we're stratifying patients and the overall economic criteria of the opt-in itself, keeping it 50-50, that could be itself a significant value-driving event that would allow us to trade to appropriate market cap to take advantage of that. So we'll have to wait and see, but I'm very confident that 25% will always be in play, and we're still reasonably confident that in many scenarios, 50-50 could also be implied. And maybe Tom can go back and remind everyone why we say that.

是的。我會以高水平開球，並讓湯姆提供更多色彩。我認為我們幾年前談判的方式是共同發展結構；第一，即使在當前 25% 的環境下，它也是非常實惠的。第二，由於我們對這一途徑幹預的了解、我們如何對患者進行分層以及選擇加入本身的總體經濟標準（保持 50-50）帶來的總體風險回報效益，這可能是它本身就是一個重要的價值驅動事件，使我們能夠交易到適當的市值以利用這一點。因此，我們必須拭目以待，但我非常有信心 25% 將始終發揮作用，而且我們仍然有理由相信，在許多情況下，也可能暗示 50-50。也許湯姆可以回去提醒大家我們為什麼要這麼說。

Yes. Thanks, Steve. And I agree with those comments about why we think that's overall target that we'd shoot for in terms of the co-development opt-in. And so just again to reiterate that 25% here, the cost of opting in, there's sort of no immediate cost or carve-back of milestones or anything for opting in. When we do that, we're still entitled to development milestones along the way for the future stages of clinical development that have sort of meaningfully offset some of the costs that we're going to have to incur. We also expect that, again, if the data readout is positive, that we would be getting credit for this. We think it's a very valuable program and being able to show that would be important. Again, if we opt in at the 50% level, there is going to be a higher cost burden because of the development milestones that we get on an ongoing basis do decrease. But again, I think the quality of the data is going to help guide and dictate along with the development plan that we get from AstraZeneca that will help guide and inform our opt-in decision.

是的。謝謝，史蒂夫。我同意這些評論，為什麼我們認為這是我們在選擇加入共同開發方面所追求的總體目標。因此，再次重申，這裡的 25%，即選擇加入的成本，沒有立即成本或里程碑的削減或任何選擇加入的東西。當我們這樣做時，我們仍然有權沿著這是臨床開發未來階段的一種方式，可以有效地抵銷我們將不得不承擔的一些成本。我們也預計，如果數據讀數是積極的，我們將因此獲得榮譽。我們認為這是一個非常有價值的項目，能夠證明這一點非常重要。同樣，如果我們選擇 50% 的水平，將會有更高的成本負擔，因為我們持續獲得的開發里程碑確實會減少。但我再次認為，數據的品質將有助於指導和規定我們從阿斯特捷利康獲得的開發計劃，這將有助於指導和告知我們的選擇加入決策。

Great. Makes sense. And then maybe one on 220. I noticed that you didn't say an IND for that. You said you have a regulatory filing. So can you talk a little bit more about what geographies you're starting developments in for the 2020 program, and how your choice -- why making the choices you're making about where to do development there?

偉大的。說得通。然後也許是 220。我注意到你沒有為此說 IND。你說你有監理備案。那麼，您能否多談談您在 2020 年計劃中開始開發的地區，以及您的選擇——為什麼要選擇在哪裡進行開發？

Yes. We didn't mention IND. We filed a CTN in Australia, and we are really repeating what we did with 060. So like 060, we filed a CTN in Australia, did healthy volunteers as a nebulized formulation with a very capable CRO. It worked really well. That time, we're going to do the same thing.

是的。我們沒有提到 IND。我們在澳洲提交了一份CTN，我們實際上是在重複我們對060 所做的事情。因此，與060 一樣，我們在澳洲提交了一份CTN，並與一位非常有能力的CRO 一起為健康志工提供了霧化製劑。效果非常好。到時候，我們也會做同樣的事情。

Great. That makes perfect sense. And then I guess, I'll also sneak one in on oncology while I've got you. The collaboration programs seem to be ongoing, they're plugging away, some things are coming into the clinic. Are there any of these that you think are particularly likely to move rapidly once they get in the clinic or have the potential to deliver near-term milestones that will help with some of your cash prioritization needs?

偉大的。這是完全有道理的。然後我想，趁著你還在，我也會偷偷地講腫瘤學。合作計畫似乎正在進行中，他們正在努力，一些東西正在進入診所。您認為其中是否有任何項目一旦進入診所就特別有可能迅速發展，或者有可能實現近期里程碑，從而有助於滿足您的一些現金優先需求？

Well, I'll let Tom talk about -- I'll talk about that as we did forecast some modest milestones for some of our cash forecasting and yes, I'll turn it over to Tom.

好吧，我會讓湯姆談談——我會談談這個，因為我們確實預測了一些現金預測的一些適度的里程碑，是的，我會把它交給湯姆。

Yes. So we did say that in terms of how we're thinking about it, and Steve used the word modest, and I would agree with that. So across the different partnerships, we have some that are earlier discovery stage and would pass some early gates. We mentioned, for example, Boston Pharma. If that program goes into the clinic as we expected, there would be some milestones for that program. But I would just sort of again characterize these as helpful milestones that support us, but they're not -- they're not, say, of the magnitude like we've seen with AstraZeneca. So just to put it in perspective, I think they're just -- they're meaningful from a development perspective to continue these programs and have our partners committed to bringing them forward and obviously, the cash does help us, but it is modest in comparison to milestones we've recorded and shown in the past.

是的。所以我們確實是根據我們的想法來這麼說的，史蒂夫用了「謙虛」這個詞，我同意這一點。因此，在不同的合作夥伴關係中，我們有一些處於早期發現階段，並且會通過一些早期關卡。例如，我們提到了波士頓製藥公司。如果該項目如我們預期進入臨床，該計畫將會有一些里程碑。但我想再次將這些描述為支持我們的有用的里程碑，但它們不是——比如說，它們的規模不像我們在阿斯特捷利康看到的那樣。因此，從長遠來看，我認為從發展的角度來看，繼續這些計劃並讓我們的合作夥伴致力於推動這些計劃是有意義的，顯然，現金確實對我們有幫助，但數額不大與我們過去記錄和展示的里程碑相比。

Our next question will come from Matt Phipps with William Blair.

我們的下一個問題將由馬特·菲普斯和威廉·布萊爾提出。

Steve, you've commented on how mapping has impacted disease control in asthma. And I'm wondering, is that just on the side of finding patients that still need certain exacerbation in FEV1 criteria? Or does that also impact what you might think a placebo arm in an FEV1 type of trial would do and therefore would require some changes to kind of maybe empower assumptions versus historical trials that happen pre-pandemic? And then more broadly, I mean if -- do you think that has any longer-term impact on the number of patients that kind of meet more of a moderate to severe qualification?

史蒂夫，您評論了繪圖如何影響氣喘疾病控制。我想知道，這是否只是為了尋找 FEV1 標準中仍需要某些惡化的患者？或者這也會影響您可能認為 FEV1 類型試驗中安慰劑組的作用，因此需要進行一些改變，以支持假設與疫情前發生的歷史試驗？更廣泛地說，我的意思是，您是否認為這對符合中度至重度資格的患者數量有任何長期影響？

Yes. Thanks, Matt. So maybe the last question I'll try to address first if there's a long-term impact here on maybe the opportunity for asthma. I don't think so. I don't think people love being masked. And I think that was part of mandates, and I think we will return to normal eventually. It just happened to hit us during the enrollment of our efficacy trial. That's just unfortunate timing. So I think even if it were to, say, overall lead to better patient control, one of the benefits of inhaled biologic that is -- remember, we say is more efficient, likely a more efficient intervention -- we have the ability to play upstream of the classically higher-cost injectable biologics. So I think if that happens, there will be no biologic better positioned to take advantage of that than something like 060. So that's something -- that's how I would be looking at navigating around a potential new normal when it comes to severity compared to historical epidemiology data.

是的。謝謝，馬特。因此，如果這對氣喘的機會有長期影響，也許我會先嘗試解決最後一個問題。我不這麼認為。我不認為人們喜歡蒙面。我認為這是任務的一部分，我認為我們最終會恢復正常。它只是在我們的功效試驗招募過程中碰巧發生了。這只是不幸的時機。因此，我認為，即使總體上可以更好地控制患者，吸入生物製劑的好處之一是——記住，我們說它更有效，可能是一種更有效的干預措施——我們有能力發揮作用傳統上成本較高的注射生物製劑的上游。所以我認為，如果這種情況發生，沒有什麼生物製劑比 060 這樣的藥物能更好地利用這一點。所以，這就是我在與歷史相比的嚴重性方面如何看待圍繞潛在新常態的方式。流行病學數據。

With respect to how the control from masking or how FEV1 and exacerbation might be improved by the masking and how that informs the power of the study, and I would say AZ certainly considered that, and we feel really good about the power of the study. There is obviously a placebo arm, it's well powered, and there is a running period of 4 weeks. So we really feel good about the baselines that we'll be using to go into the trial. I think we think that the criteria actually address both ends maybe of the control spectrum. When we talk about the inclusion exclusion criteria amendments that we are making or AZ is making. So for example, we're modifying the FEV1 inclusion criteria from 60% to 80% to 50% to 85%. So patients who have less control or reduced function then will currently be allowed to come into the trial. They would now then be able to come into the trial. And I think that would actually do the opposite of what you suggested could happen if we were dealing with much more controlled patients in general.

關於如何透過遮蔽進行控制，或者如何透過遮蔽來改善 FEV1 和惡化，以及如何體現研究的力量，我想說 AZ 肯定考慮到了這一點，我們對這項研究的力量感到非常滿意。顯然有一個安慰劑臂，它動力充足，並且有 4 週的運行期。因此，我們對用於試驗的基線感到非常滿意。我認為我們認為這些標準實際上解決了控制範圍的兩端。當我們談論我們正在製定或 AZ 正在製定的納入排除標準修訂時。例如，我們將 FEV1 納入標準從 60% 修改為 80%，修改為 50% 至 85%。因此，控制能力較差或功能減弱的患者目前將被允許參加試驗。他們現在就可以參加審判了。我認為，如果我們處理的是整體上受到更多控制的患者，這實際上會與您所建議的情況相反。

We are also in that vein, allowing high dose as well as medium dose ICS/LABA combinations going forward, which also, I think, shows that we feel really good about how we're powering the study. There are a couple of other things that are maybe getting rid of unforced errors like separate ICS and LABA devices are now allowed rather than mandating a combination. But back to a couple of other things that reflect maybe what -- how the masking has changed things [temporally], looking more retrospectively at patient control, things like demonstrating a reversibility either at screening or within 5 years is another change. And then lastly, exacerbations. Typically, you see trials where you look at an exacerbation in the last year or maybe 2 years. With the amendments, it will be changed to exacerbations within the last 3 years rather than 1 year. And so those are, I think, collectively allowing us to get patients who historically had poor control before masking and also allowing the enrollment based on patients who have worse control than would be allowed to be enrolled in the trial today.

我們也遵循這一思路，允許繼續使用高劑量和中劑量的 ICS/LABA 組合，我認為這也表明我們對如何推動這項研究感到非常滿意。還有一些其他事情可能會消除非受迫性錯誤，例如現在允許使用單獨的 ICS 和 LABA 設備，而不是強制組合。但回到其他一些可能反映什麼的事情——掩蔽如何[暫時]改變事情，更回顧性地審視患者的控制，例如在篩檢或 5 年內證明可逆性是另一個變化。最後，病情加重。通常，您會看到去年或兩年內病情惡化的試驗。修訂後，病情加重由一年改為近三年內。因此，我認為，這些共同允許我們在掩蓋之前獲得歷史上控制不佳的患者，並允許根據控制能力比今天允許參加試驗的患者更差的患者進行招募。

Okay. Thanks for the additional details. One last one, on the 344, will you present any data before you move into the expansion cohorts?

好的。感謝您提供更多詳細資訊。最後一個問題是，在 344 上，您在進入擴展隊列之前會提供任何資料嗎？

We can't definitively say because it depends on our timing to escalate. It depends on how that aligns with medical or scientific conferences and also might depend on if we're going forward with like an estimated optimal biologic dose, which is likely compared to, say, NTD. We certainly want to make sure that given the capital-constrained environment that we all find ourselves in, in biotech that investors and analysts understand that there would be a sound rationale for why we would move into expansion. So I think finding some way to communicate that, whether that's at a medical conference beforehand or top line description or otherwise, that remains to be determined. But I would say we have clear plans on where to go when the time is right, and we look forward to continuing the escalation, which is going quite well with Servier to be able to make that decision towards the end of the year, hopefully.

我們不能明確地說，因為這取決於我們升級的時間。這取決於它如何與醫學或科學會議保持一致，也可能取決於我們是否繼續估計最佳生物劑量，這可能與 NTD 等進行比較。我們當然希望確保，考慮到我們所有人都所處的資本受限環境，在生物技術領域，投資者和分析師都明白，我們有一個合理的理由來解釋為什麼我們要擴張。因此，我認為找到某種方式來傳達這一點，無論是在事先的醫學會議上還是在頂線描述或其他方式上，這仍有待確定。但我想說的是，我們對於時機成熟時的發展方向有明確的計劃，我們期待著繼續升級，施維雅進展順利，希望能夠在今年年底做出決定。

All right. Ladies and gentlemen, at this time, there are no further questions in queue. (Operator Instructions)

好的。女士們、先生們，目前沒有其他問題了。 （操作員說明）

And I see nobody joining the queue. So now turn it over to Steve Yoder for closing remarks.

我看到沒有人加入隊列。現在請史蒂夫尤德 (Steve Yoder) 發表結束語。

I just want to say thanks, everyone, for joining and for your attention today and your continued support to Pieris. Have a great day.

我只想感謝大家今天的加入、關注以及對 Pieris 的持續支持。祝你有美好的一天。

Once again, ladies and gentlemen, this concludes your call. You may now disconnect your lines, and thank you for joining us today.

女士們先生們，你們的通話到此結束。現在您可以斷開線路，感謝您今天加入我們。