Palvella Therapeutics Inc (PVLA) 2022 Q3 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Pieris Pharmaceuticals, Inc. Third Quarter Earnings Call. (Operator Instructions)

女士們、先生們，美好的一天，歡迎參加 Pieris Pharmaceuticals, Inc. 第三季財報電話會議。 （操作員說明）

At this time, it is my pleasure to turn the floor over to your host, Tom Bures. Sir, the floor is yours.

現在，我很高興將發言權交給東道主湯姆布雷斯。先生，地板是你的了。

Thank you. Good morning, everyone, and thank you for joining us for our third 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. You can access the press release released this morning on the Investor Relations page of our website at www.pieris.com.

謝謝。大家早安，感謝您參加我們的 2022 年第三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。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 the 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 third quarter 2022 earnings call. Today, I will give an update on how our lead programs are progressing, what upcoming catalysts to expect and exciting new programs we have announced recently. We are driving towards numerous catalysts and inflection points over the next year across both our respiratory and our IO franchises.

謝謝湯姆，也謝謝大家今天參加我們的 2022 年第三季財報電話會議。今天，我將介紹我們的主導項目的進展、即將到來的催化劑以及我們最近宣布的令人興奮的新項目。明年，我們的呼吸和 IO 特許經營業務將迎來眾多催化劑和轉折點。

More specifically within respiratory, in addition to preparing for the Phase IIa readout and subsequent opt-in decision for elarekibep, also known as PRS-060 or AZD1402, we are advancing a pipeline of wholly owned, highly differentiated, inhaled respiratory products. Similarly, within IO, we are expecting to have initiated expansion of PRS-344 in co-development with Servier while anticipating clinical starts of 4-1BB-based IO assets by collaborators Seagen and Boston Pharmaceuticals as we continue to be a leader in the realm of targeted 4-1BB costimulation. By early next year, we expect there will be 3 4-1BB Mabcalin, or antibody-Anticalin fusion bispecifics, in active clinical development. But before I go into these details, I will give a more in-depth overview on the respiratory franchise.

更具體地說，在呼吸領域，除了為elarekibep（也稱為PRS-060 或AZD1402）的IIa 期讀數和隨後的選擇決定做準備外，我們還在推進全資、高度差異化的吸入呼吸產品的管道。同樣，在 IO 領域，我們預計將與 Servier 共同開發 PRS-344 的擴展，同時預計合作者 Seagen 和 Boston Pharmaceuticals 開始基於 4-1BB 的 IO 資產的臨床，因為我們將繼續成為該領域的領導者目標4 -1BB 共刺激。到明年初，我們預計將有 3 種 4-1BB Mabcalin 或抗體-Anticalin 融合雙特異性藥物處於積極的臨床開發中。但在詳細介紹這些細節之前，我將對呼吸系統產品進行更深入的概述。

In the Phase IIa trial of the dry powder formulated elarekibep, an inhaled IL-4 receptor alpha inhibitor that we are developing with AstraZeneca for the treatment of moderate to severe asthma, I'm pleased to report that AstraZeneca has completed the enrollment of Part 1b, which is the safety of the 10 mg cohort, while enrollment continues for Part 2, which is efficacy of the 3 mg cohort versus placebo.

在乾粉配方elarekibep 的IIa 期試驗中，我們正在與阿斯特捷利康共同開發一種吸入性IL-4 受體α 抑制劑，用於治療中度至重度氣喘，我很高興地報告阿斯特捷利康已完成第1b 部分的入組，這是 10 mg 隊列的安全性，而第 2 部分繼續入組，這是 3 mg 隊列與安慰劑的療效。

AstraZeneca also is making great strides in addressing enrollment challenges encountered for the efficacy portion of this study. During last quarter's earnings update, we announced that AstraZeneca was pursuing regulatory and ethical submission across all jurisdictions where the study is active with the objective of improving speed of enrollment and focusing enrollment into the 3 mg cohort. AstraZeneca has since completed these submissions in all territories with acceptance and implementation tracking according to expectations.

阿斯特捷利康在解決本研究有效性部分所遇到的入組挑戰方面也取得了長足進步。在上季度的收益更新中，我們宣布阿斯特捷利康正在研究活躍的所有司法管轄區尋求監管和道德提交，目的是提高入組速度並將入組重點納入 3 mg 隊列。此後，阿斯特捷利康已在所有地區完成了這些提交，並根據預期進行了驗收和實施追蹤。

With these changes being implemented, top line results from this study are expected to be recorded in third quarter of next year. These results will include the safety data of the 1 mg, 3 mg and 10 mg dose cohorts and efficacy data from the 3 mg cohort. As a reminder, the primary endpoint in this study is FEV1 improvement at 4 weeks versus placebo. This important data set, alongside a development plan and a budget from AstraZeneca, will trigger an opt-in decision for either 25% or 50% of cost sharing. Being in a strong position to opt in if data are positive remains one of the highest company priorities for the coming year.

隨著這些變化的實施，這項研究的主要結果預計將在明年第三季公佈。這些結果將包括 1 mg、3 mg 和 10 mg 劑量組的安全性數據以及 3 mg 組的療效數據。提醒一下，本研究的主要終點是 4 週時 FEV1 與安慰劑相比的改善。這一重要的資料集與阿斯特捷利康的開發計劃和預算一起，將觸發 25% 或 50% 成本分攤的選擇加入決策。如果數據積極，那麼處於有利位置選擇加入仍然是公司來年的最高優先事項之一。

Also within the AstraZeneca alliance, we do continue to advance 2 discovery stage programs alongside elarekibep. We retain co-development and U.S. co-commercialization options for these 2 programs.

同樣在阿斯特捷利康聯盟內，我們繼續與 elarekibep 一起推進 2 個發現階段項目。我們保留這兩個項目的共同開發和美國共同商業化選項。

I would now like to spend some time discussing the fully proprietary inhaled respiratory programs we are developing, PRS-220 and PRS-400, given that the data we have generated so far with elarekibep have strengthened our conviction in the validity and differentiation of our inhaled therapeutic protein approach. Earlier this week, we announced the dosing of the first subject in the Phase I study of PRS-220, an inhaled Anticalin protein targeting connective tissue growth factor, or CTGF, for the treatment of idiopathic pulmonary fibrosis and other forms of fibrotic lung disease.

我現在想花一些時間討論我們正在開發的完全專有的吸入式呼吸系統PRS-220 和PRS-400，因為迄今為止我們與elarekibep 生成的數據增強了我們對吸入式呼吸系統的有效性和差異化的信念。治療性蛋白質方法。本週早些時候，我們宣布了PRS-220 I 期研究中第一位受試者的給藥，PRS-220 是一種吸入性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和其他形式的纖維化肺部疾病。

The study will evaluate the safety, tolerability and pharmacokinetics of an oral inhaled nebulized formulation of PRS-220 in healthy volunteers. This is the second inhaled Anticalin-based programs we are bringing into the clinic, and we expect to report the outcome of this study next year. As a reminder, this work is partially funded by a grant from the Bavarian Ministry of Economic Affairs , Regional Development and Energy?, within the framework of the Bavarian Therapy Strategy to combat the COVID-19 pandemic, or also known as BayTherapie2020.

研究將評估 PRS-220 口服吸入霧化製劑在健康志願者中的安全性、耐受性和藥物動力學。這是我們將基於 Anticalin 的吸入療法引入臨床的第二個項目，我們預計明年將報告這項研究的結果。提醒一下，這項工作的部分資金來自巴伐利亞經濟事務、區域發展和能源部的撥款，在巴伐利亞對抗 COVID-19 大流行的治療策略（也稱為 BayTherapie2020）的框架內。

Beyond PRS-220, we recently unveiled another proprietary inhaled respiratory program at the 2022 European Respiratory Society's International Congress called PRS-400, which is an inhaled Jagged-1 antagonist we are developing for the treatment of muco-obstructive lung diseases. A wealth of third party data supports that upregulation of the Jagged-1 Notch signaling can cause goblet cell metaplasia, hyperplasia, mucus hypersecretion and mucus plugging. Also shows that downregulation of this pathway can drive goblet cells toward a ciliary phenotype. However, systematically administered drugs targeting Notch signaling have caused systemic side effects and tolerability issues such as GI toxicities.

除了PRS-220 之外，我們最近在2022 年歐洲呼吸學會國際大會上推出了另一個專有的吸入呼吸計劃，稱為PRS-400，它是我們正在開發的一種吸入式Jagged-1 拮抗劑，用於治療黏膜阻塞性肺部疾病。大量第三方數據支持 Jagged-1 Notch 訊號傳導的上調可導致杯狀細胞化生、增生、黏液分泌過多和黏液堵塞。也顯示該途徑的下調可以驅動杯狀細胞向睫狀體表型發展。然而，系統性施用針對Notch訊號傳導的藥物已引起系統性副作用和耐受性問題，例如胃腸道毒性。

PRS-400 is designed to block JAG1 Notch signaling locally in the lung via oral inhalation with the objective of reversing, independent of stimulus, goblet cell metaplasia, hyperplasia and mucus plugging as well as increasing the number of ciliated cells. Preclinical data presented at ERS showed that in vitro, multiple PRS-400 drug candidates can penetrate mucus-coated epithelia to potently inhibit JAG1-induced signaling on lung epithelial cells, thereby reducing mucin expression. We also achieved in vivo proof of concept with PRS-400 candidates in an IL-13 induced mucus hypersecretion mouse model, not only by significantly improving mucus score and reducing goblet cell numbers, but also by significantly increasing a key marker of ciliary cells.

PRS-400 旨在透過口腔吸入在肺部局部阻斷 JAG1 Notch 訊號傳導，目的是在不受刺激的情況下逆轉杯狀細胞化生、增生和黏液堵塞，並增加纖毛細胞的數量。 ERS 上公佈的臨床前數據表明，在體外，多種 PRS-400 候選藥物可以穿透黏液包被的上皮細胞，有效抑制 JAG1 誘導的肺上皮細胞信號傳導，從而減少黏蛋白表達。我們還在IL-13 誘導黏液分泌過多的小鼠模型中實現了PRS-400 候選物的體內概念驗證，不僅顯著提高了黏液評分並減少了杯狀細胞數量，而且還顯著增加了睫狀細胞的關鍵標記物。

We are excited about this program because it follows the same local treatment approach via inhalation we are taking with elarekibep and PRS-220. Moreover, JAG1 represents a highly translatable target that we believe has significant potential to treat a variety of muco-obstructive diseases, and there is a strong rationale for a local inhaled intervention given the desire to avoid GI toxicities. We are continuing to work on this program in preclinical work and look forward to giving further updates in due course.

我們對該計劃感到興奮，因為它遵循與我們使用 elarekibep 和 PRS-220 相同的吸入局部治療方法。此外，JAG1 代表了一個高度可轉化的靶點，我們認為它具有治療多種黏膜阻塞性疾病的巨大潛力，考慮到避免胃腸道毒性的願望，局部吸入乾預有充分的理由。我們正在繼續進行該計畫的臨床前工作，並期待在適當的時候提供進一步的更新。

Turning now to our IO franchise. Our Mabcalin bispecifics pipeline also has some exciting updates, including a new partnered program announcement and upcoming first-in-human trial starts for program -- multiple partnered programs. First, I want to note that enrollment of the dose escalation portion of the Phase I/II study of PRS-344, or S095012, remains ongoing. PRS-344 is a 4-1BB/PD-L1 Mabcalin bispecific for the treatment of solid tumors we are developing in co-development with Servier, and it is our lead IO program. We expect to present data from the study at a medical meeting next year for this program. As a reminder, we retain full U.S. rights for this program, and we will receive royalties on any ex-U.S. sales. Beyond PRS-344, Servier is continuing development of PRS-352, or S095025, which is an OX40/PD-L1 bispecific for which Servier has global rights.

現在轉向我們的 IO 特許經營權。我們的 Mabcalin 雙特異性藥物管道也有一些令人興奮的更新，包括新的合作項目公告和即將開始的項目首次人體試驗 - 多個合作項目。首先，我想指出 PRS-344 或 S095012 I/II 期研究的劑量遞增部分的招募仍在進行中。 PRS-344 是一種 4-1BB/PD-L1 Mabcalin 雙特異性藥物，用於治療實體瘤，我們正在與 Servier 共同開發，它是我們的主導 IO 計畫。我們預計將在明年該計畫的醫學會議上展示該研究的數據。提醒一下，我們保留該計劃在美國的全部權利，並且我們將收到任何美國以外地區的特許權使用費。銷售量。除了 PRS-344 之外，施維雅也持續開發 PRS-352（即 S095025），這是施維雅擁有全球權利的 OX40/PD-L1 雙特異性藥物。

We also continue to work on a number of programs as part of our IO collaboration with Seagen, and I am pleased to announce the unveiling of the first of those programs, which is SGN-BB228, also known as PRS-346, at the upcoming SITC conference next week. SGN-BB228 is a first-in-class 4-1BB/CD228 bispecific Mabcalin compound. The IND for the Phase I study for this program has recently been accepted, and Seagen plans to initiate the study in the coming months, at which point we will receive a milestone payment from Seagen. Beyond this program, Seagen continues to develop a second undisclosed bispecific program and has recently nominated the third bispecific program for initiation within the collaboration. As a reminder, we have a U.S. co-promotion option for 1 program in this 3 program collaboration.

作為與 Seagen IO 合作的一部分，我們也繼續致力於許多項目，我很高興地宣佈在即將舉行的 IO 大會上推出了第一個項目，即 SGN-BB228，也稱為 PRS-346. SITC 會議下週。 SGN-BB228 是一流的 4-1BB/CD228 雙特異性馬布卡林化合物。該專案 I 期研究的 IND 最近已被接受，Seagen 計劃在未來幾個月內啟動研究，屆時我們將收到 Seagen 的里程碑付款。除了該計劃之外，Seagen 還在繼續開發第二個未公開的雙特異性計劃，並於最近提名了第三個雙特異性計劃在合作中啟動。提醒一下，我們在這 3 個專案合作中為 1 個專案提供了美國聯合推廣選項。

Turning to our most recent IO partnership. In the next 6 months, we also expect the initiation of the Phase I study of PRS-342, or BOS-342, which is a 4-1BB/GPC3 bispecific Mabcalin compound licensed by Boston Pharmaceuticals, which is being developed in solid tumors. Both the Seagen program and the Boston Pharmaceuticals program represent a broadening of our clinical 4-1BB footprint in immuno-oncology, and we are excited to have the support of our many partners in advancing the various applications of the Anticalin technology. Among these several partners is Genentech, with whom we signed a discovery stage collaboration for 1 respiratory target and 1 ophthalmology target last year and which continues to progress. In addition to contributing R&D know-how and resources, our partnerships have served and continue to serve as an important source of non-dilutive capital, the importance of which cannot be overstated in these current markets.

談談我們最近的 IO 合作夥伴關係。在接下來的6 個月內，我們也預計將啟動PRS-342 或BOS-342 的I 期研究，PRS-342 是波士頓製藥公司許可的4-1BB/GPC3 雙特異性Mabcalin 化合物，正在實體瘤中開發。 Seagen 計畫和 Boston Pharmaceuticals 計畫都代表了我們在免疫腫瘤學領域臨床 4-1BB 足跡的拓寬，我們很高興能得到許多合作夥伴的支持，推動 Anticalin 技術的各種應用。這些合作夥伴包括基因泰克 (Genentech)，我們去年與他們簽署了針對 1 個呼吸標靶和 1 個眼科標靶的發現階段合作，並且該合作仍在繼續取得進展。除了貢獻研發知識和資源外，我們的合作關係已經並將繼續成為非稀釋資本的重要來源，其重要性在當前市場中怎麼強調都不為過。

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

我準備好的演講到此結束，現在我想將電話轉回湯姆。

Thank you, Steve, and good morning again, everybody.

謝謝你，史蒂夫，大家早安。

Cash and cash equivalents and investments totaled $69.8 million for the quarter ended September 30, 2022, compared to a cash and cash equivalents balance of $117.8 million for the quarter ended December 31, 2021. The decrease in cash is due to funding operations in the current year. Including the proceeds from anticipated near-term milestones, we will continue to make disciplined pipeline investments that demonstrate our commitment to achieve multiple inflection points across our clinical program in the next year, and we believe this cash balance provides sufficient funding into the second quarter of 2024.

截至 2022 年 9 月 30 日的季度現金和現金等價物及投資總額為 6,980 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。現金減少是由於當前的融資業務年。包括預期近期里程碑的收益在內，我們將繼續進行嚴格的管道投資，以證明我們致力於在明年實現整個臨床項目的多個拐點，我們相信這一現金餘額為第二季度提供了足夠的資金2024年。

R&D expenses were $13.6 million for the quarter ended September 30, 2022, compared to $18.9 million for the quarter ended September 30, 2021. The decrease is due to lower program costs as work related to the company's sponsored Phase I trial of elarekibep was largely completed in 2021 as well as due to lower manufacturing costs across all later stage respiratory and immuno-oncology programs and lower consulting costs. These lower costs were partially offset by higher clinical costs for PRS-344, or S095012, higher preclinical costs for earlier stage programs and an increase in personnel costs.

截至2022年9月30日的季度研發費用為1360萬美元，而截至2021年9月30日的季度研發費用為1890萬美元。這一下降是由於與公司贊助的elarekibep第一期試驗相關的工作已基本完成，因此項目成本降低。2021 年，由於所有後期呼吸系統和免疫腫瘤學項目的製造成本降低以及諮詢成本降低。這些較低的成本被 PRS-344 或 S095012 較高的臨床成本、早期項目較高的臨床前成本以及人員成本的增加部分抵消。

G&A expenses were $3.9 million for the quarter ended September 30, 2022, compared to $4.1 million for the quarter ended September 30, 2021. The period-over-period decrease was driven primarily by lower professional service costs and lower facilities costs, partially offset by higher travel expenses.

截至 2022 年 9 月 30 日的季度，一般及行政費用為 390 萬美元，而截至 2021 年 9 月 30 日的季度為 410 萬美元。同比下降主要是由於專業服務成本和設施成本下降，部分被更高的旅行費用。

And finally, for other income, for the quarter ended September 30, 2022, $1.5 million of grant income was recorded with respect to PRS-220 compared to $1.8 million for the quarter ended September 30, 2021. The decrease is due to lower overall costs incurred this quarter on PRS-220 compared to the same quarter in the prior year.

最後，對於其他收入，截至 2022 年 9 月 30 日的季度，PRS-220 記錄了 150 萬美元的補助收入，而截至 2021 年 9 月 30 日的季度為 180 萬美元。減少的原因是總體成本降低與去年同期相比，本季PRS-220 產生的費用。

Overall, net loss was $9.7 million, or a $0.13 loss per share, for the quarter ended September 30, 2022, compared to a net loss of $16.5 million, or a $0.24 loss per share, for the quarter ended September 30, 2021.

整體而言，截至2022 年9 月30 日的季度淨虧損為970 萬美元，即每股虧損0.13 美元，而截至2021 年9 月30 日的季度淨虧損為1,650 萬美元，即每股虧損0.24 美元。

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

這樣，我會將電話轉回給史蒂夫。

Thank you, Tom. We would now like to open the call for your questions.

謝謝你，湯姆。我們現在想開始電話詢問您的問題。

(Operator Instructions) Our first question comes from Jonathan Miller with Evercore.

（操作員說明）我們的第一個問題來自 Evercore 的 Jonathan Miller。

Congrats on all the progress, especially all the collaboration progress. I just wanted to -- maybe a couple housekeeping things. The runway that you -- runway guidance you've given, what clinical development, what internal clinical development does that include? Which of those programs, especially the ones that are slated to enter the clinic, are you funding through that runway? And sort of relatedly, you said that the middle PRS-060 opt-in level is quite easy for you to fund. Is there any risk to your ability to fund that next year, or are you really thinking about whether you can afford the higher opt-in level?

祝賀所有的進展，特別是所有的合作進展。我只是想做一些家事。您提供的跑道指導，包括哪些臨床開發、哪些內部臨床開發？您正在透過該跑道資助哪些項目，尤其是那些計劃進入診所的項目？與此相關的是，您說過中間的 PRS-060 選擇加入等級對您來說很容易資助。您明年的資助能力是否有任何風險，或者您是否真的考慮是否能夠負擔更高的選擇加入程度？

Jon, it's Steve. Thanks for the questions. I'll turn it over to Tom to cover these, and then I can fill in with anything that you have residual questions on.

喬恩，我是史蒂夫。感謝您的提問。我會把它交給湯姆來解決這些問題，然後我可以填寫您還有剩餘問題的任何內容。

Yes. Thanks, Jon. Yes, so the runway includes the ongoing 220 and 344 along with 060 costs. So those are the primary clinical assets that we have, and so those are the key to our sort of SG&A playing and continued development there. So again, a reminder that 060 right now, there's really limited costs on our books because that's all being funded by AstraZeneca. For 220, our costs are supported by the Bavarian government that we referred to, the grant that we received, and that's been really helpful in terms of pushing that forward and getting that into the clinic as we just announced. So that's great progress there, and we appreciate their support. And then also 344 partnered with Servier. So about just under 50% funded by Servier there. So very cost efficient strategy, and that's how we continue to budget this out. For those other assets that we referred to in IO moving into the clinic, those are out licensed, so we have no cost obligation related to those. So those would just be the partners' cost. So that could be, again, next year, 5 clinical stage assets, and we're paying for about the total of 1.

是的。謝謝，喬恩。是的，所以跑道包括正在進行的 220 和 344 以及 060 的成本。這些是我們擁有的主要臨床資產，也是我們 SG&A 發揮和持續發展的關鍵。再次提醒大家，060 目前，我們帳簿上的成本確實有限，因為這一切都是由阿斯特捷利康資助的。對於 220，我們的費用得到了我們提到的巴伐利亞政府的支持，即我們收到的贈款，這對於推動這一進程並將其進入診所非常有幫助，正如我們剛剛宣布的那樣。這是巨大的進步，我們感謝他們的支持。然後344也與施維雅合作。因此，大約有不到 50% 的資金是由施維雅資助的。這是非常具有成本效益的策略，這就是我們繼續制定預算的方式。對於我們在 IO 中提到的其他進入診所的資產，這些資產已獲得許可，因此我們沒有與這些資產相關的成本義務。所以這些只是合作夥伴的成本。因此，明年可能會有 5 項臨床階段資產，而我們總共支付約 1 項資產。

I believe your second question related to the opt-in for PRS-060. And right, like you mentioned, I think we continue to focus on the opt-in at the 25% believing, again, that is manageable, given that sort of the spread of the costs, along with the -- our share of development milestones that we would continue to get on that program that are meaningful to us, it's something that we think is, again, relatively affordable. We do have to think about, of course, the capital allocation across our programs. And I think if we were thinking about opting in at a higher level, I think that's going to be based upon the quality of the top line results and how good those are, and really the credit I think that we're going to be able to get hopefully externally for this program and moving into that clinical readout.

我相信您的第二個問題與選擇加入 PRS-060 有關。是的，就像你提到的，我認為我們繼續關注 25% 的選擇加入，再次相信，考慮到成本的分散，以及我們在開發里程碑中所佔的份額，這是可以管理的我們將繼續參加對我們有意義的計劃，我們再次認為這是相對負擔得起的。當然，我們確實必須考慮各個項目的資本分配。我認為，如果我們考慮選擇更高的水平，我認為這將基於頂線結果的品質以及這些結果的好壞，以及我認為我們將能夠獲得的信用希望能夠從外部獲得該計劃並進入臨床讀數。

Yes. Thanks, Tom, for that. The only color I would add to the second question is just to remind everyone that the opt-in decision that we have, which is at our discretion and could be not at all, which we would not want to do, or 25% or 50%, we do not have to make that decision until after the top line data are revealed and we can talk about them, as well as a go-forward plan and budget. So the external stakeholders will certainly have the ability to digest all of that. And there could be reasons, as Tom said, the data alone could be a basis for appreciation in value that allow us to opt in at a higher level than 25%. And of course, there are things independent, extrinsic to PRS-060 that would create value in the company. That's why we have multiple programs, multiple franchises and several partnerships. So when we consider the landscape of potential catalysts next year, and the core being PRS-060 Phase IIa, but several other things, we are very encouraged about the ability to opt in, whether that's at 25% or beyond.

是的。謝謝你，湯姆。我要為第二個問題添加的唯一顏色只是提醒大家，我們的選擇加入決定是由我們自行決定的，也可能根本不是我們不想做的，或者 25% 或 50 ％，我們不必做出決定，直到頂線數據公佈之後我們可以討論它們，以及前進的計劃和預算。因此，外部利害關係人肯定有能力消化所有這些。正如湯姆所說，可能有一些原因，僅憑數據就可以成為價值升值的基礎，使我們能夠選擇高於 25% 的水平。當然，還有一些獨立於 PRS-060 之外的東西可以為公司創造價值。這就是我們擁有多個項目、多個特許經營權和多個合作夥伴關係的原因。因此，當我們考慮明年潛在催化劑的前景時，核心是 PRS-060 IIa 階段，但還有其他一些事情，我們對選擇加入的能力感到非常鼓舞，無論是 25% 還是更高。

Great. Great. That makes sense. And then maybe on PRS-220, the data next year in healthy volunteers, what can we expect to learn from that from a translation perspective? I understand there's not really good biomarkers, other than just targeting IPF. Can you get on target PD? Can you get some other measure out of that healthy volunteer study that will give you good confidence in your ability to deliver for patients?

偉大的。偉大的。這就說得通了。然後也許在 PRS-220 上，明年在健康志願者中的數據，從翻譯的角度我們可以期望從中學到什麼？我知道除了針對 IPF 之外，沒有真正好的生物標記。你能達到目標PD嗎？您能否從健康志願者研究中獲得一些其他衡量標準，讓您對自己為患者提供服務的能力充滿信心？

Yes, Jon. It's a great question. At a high level, I would frame what we're going to be looking at at the end of the Phase I study next year is the set of the data that we're going to be generating, SAD/MAD data in healthy subjects, which will not have -- I think we've already mentioned that -- not have a wealth of biomarker data. And we know that that is a challenge with this particular intervention. However, we have 2 other important data sets that I want to keep in mind. One is the FibroGen pamrevlumab data. The data will read out. We know that they've enrolled the trial. We expect the pamrevlumab top line data to come out of the Phase III study about the same time, probably from mid next year. And we are working hard to generate a lot of preclinical data in parallel with our own program and benchmarking against other relevant controls. So when we have all of that, we will feel, I hope, very confident with the goal that we would make on moving forward into Phase II and also the dose. And Shane is online, and Shane can also comment a bit more on the types of nuances that one might be looking for beyond the SAD/MAD safety/tolerability data from our study. Shane?

是的，喬恩。這是一個很好的問題。在高水平上，我會框架我們將在明年第一階段研究結束時關注的是我們將生成的數據集，健康受試者的 SAD/MAD 數據，我想我們已經提到過，它不會擁有豐富的生物標記數據。我們知道，對於這種特殊的干預措施來說，這是一個挑戰。然而，我想記住另外 2 個重要的數據集。一是 FibroGen pamrevlumab 資料。數據將被讀出。我們知道他們已經參加了試驗。我們預計 pamrevlumab 的第一線數據將在大約同一時間（可能從明年中期）從 III 期研究中得出。我們正在努力與我們自己的計劃並行產生大量臨床前數據，並針對其他相關控制進行基準測試。因此，當我們擁有所有這些時，我希望我們對進入第二階段的目標和劑量非常有信心。 Shane 在線，Shane 還可以對我們研究中 SAD/MAD 安全性/耐受性數據之外的細微差別類型進行更多評論。謝恩？

Yes. Thanks, Steve. So they're the fundamental things that we wanted to see in this study, but of course, we'll also look at things, some things like taste. We'll look at the PK exposure just to confirm that it's in line with what we have modeled. And then as Steve said, as we build out the preclinical data set, we'll continue to model what we believe to be the most efficacious doses based on our understanding of the molecule or understanding of Anticalins as inhaled medicaments. And also, of course, keeping an eye on that -- those trial readouts such as the pamrevlumab one, which will come mid next year, we'll keep an eye on the emergence starting to occur. And of course, consider any additional data that we can build to support our differentiated mechanism of action, but also to support the most effective Phase II study design.

是的。謝謝，史蒂夫。所以它們是我們想在這項研究中看到的基本東西，但當然，我們也會專注在一些東西，例如味道。我們將查看 PK 曝光，以確認它與我們建模的內容一致。然後，正如史蒂夫所說，當我們建立臨床前數據集時，我們將根據我們對分子的理解或對 Anticalins 作為吸入藥物的理解，繼續對我們認為最有效的劑量進行建模。當然，也要密切注意那些試驗數據，例如將於明年年中發布的 pamrevlumab 試驗數據，我們將密切關注開始出現的情況。當然，請考慮我們可以建立的任何其他數據來支持我們的差異化作用機制，同時也支持最有效的第二階段研究設計。

Our next question comes from Matt Phipps with William Blair.

我們的下一個問題來自馬特·菲普斯和威廉·布萊爾。

I guess just curious on 344 for data next year. Could you remind us just is there any preference as far as tumor types for enrollment or PD-L1 expression levels? And then will the data next year just be from dose escalation, or do you think you'll also start to get into some expansion cohorts?

我想只是對 344 明年的數據感到好奇。您能否提醒我們，就入組腫瘤類型或 PD-L1 表現量而言，是否有任何偏好？那麼明年的數據只是來自劑量遞增，還是您認為您也會開始進入一些擴展隊列？

Thanks, Matt. I'll have an overview here before I turn it over to Shane on your question in more detail. For the time lines, as a reminder, we're currently still in escalation. We're pleased with the pace of escalation so far as planned. And based on certain predetermined go signals that we would want to see to initiate expansion, we believe that that's something we would be doing next year. And there's a range of -- there's a corridor based on data sets that we would want to generate beforehand. And that could be early to mid, late next year depending on the set, and we're going to be data driven on that. That's really important. So when we think about data next year, I think you should be thinking about that as escalation data. I would note, though, that the protocol does allow for backfilling, and as we would go to expansion, we would still have the ability to utilize backfilling options. So we would have potentially meaningful data, PD clinical data that would also be meaningful to inform why we would have made a go in the first place into expansion as well as a rationale for why we're picking certain tumor types in expansion. And at that time, when we announced a go in expansion, I think that would be a good time for us to acknowledge why we're going into certain indications and put more color on those specific indications, why they emerge as a priority for us. I mean, Shane can comment on some of the nuances you mentioned. Are there any preferential tumors being enrolled? Are there any PD-1 cutoff -- PD-L1 cutoffs? So Shane, I'll turn it over to you for some of those nuances on the trial.

謝謝，馬特。在將您的問題更詳細地轉交給 Shane 之前，我將在這裡進行概述。對於時間線，提醒一下，我們目前仍在升級中。我們對迄今為止按計劃升級的速度感到滿意。基於我們希望看到的某些預定的訊號來啟動擴張，我們相信這是我們明年要做的事情。有一個基於我們想要預先生成的數據集的走廊。這可能是明年年初到中期、年底，取決於具體情況，我們將以此為數據驅動。這真的很重要。因此，當我們明年考慮數據時，我認為您應該將其視為升級數據。不過，我要指出的是，該協議確實允許回填，並且當我們進行擴展時，我們仍然能夠利用回填選項。因此，我們將獲得潛在有意義的數據，PD 臨床數據，這些數據也將有意義地告訴我們為什麼我們首先要進行擴張，以及為什麼我們在擴張中選擇某些腫瘤類型的理由。那時，當我們宣布進行擴張時，我認為這將是我們承認為什麼我們要進入某些適應症並為這些特定適應症添加更多色彩，為什麼它們成為我們的優先事項的好時機。我的意思是，肖恩可以對你提到的一些細微差別發表評論。有沒有優先入組的腫瘤？是否存在 PD-1 截止值－PD-L1 截止值？所以謝恩，我會把審判中的一些細微差別交給你。

Yes, certainly. Thanks, Steve, and hi, Matt. So in terms of the dose escalation, so we are not -- we do not have a PD-L1 cutoff from that perspective. We are also enrolling all comer solid tumors into the study. Now why are we doing that? We don't want to be overly prescriptive in terms of picking -- selecting an indication for this purpose -- or sorry, for the stage of the study. We also want to be very efficient in terms of moving through the cohorts. As Steve said, the study is going well. We are certainly benefiting from all of our knowledge gained on PRS-343. We're also benefiting from all the biomarker assays we had set up, having that institutional knowledge in terms of what are meaningful modulations on several of these biomarkers. With regards to Steve mentioned the backfilling option. So we do have backfilling options in our cohorts. We can, if we choose to, bias those towards particular indications.

是的，當然了。謝謝，史蒂夫，嗨，馬特。因此，就劑量遞增而言，我們沒有——從這個角度來看，我們沒有 PD-L1 截止值。我們也將所有角落實體瘤納入研究。現在我們為什麼要這樣做？我們不想在選擇方面過於規範——為此目的選擇一個適應症——或者抱歉，對於研究階段。我們還希望在隊列移動方面非常有效率。正如史蒂夫所說，研究進展順利。我們當然受益於我們在 PRS-343 上所獲得的所有知識。我們也受益於我們建立的所有生物標記檢測，在對其中幾種生物標誌物進行有意義的調節方面擁有機構知識。關於史蒂夫提到的回填選項。因此，我們的隊列中確實有回填選項。如果我們選擇的話，我們可以將這些偏向特定的適應症。

With regards to the speed with which we will move from escalation to expansion, as Steve indicated, there is a bit of a dose range there that, as you know from the competitive programs, what we're looking for here is optimal biological dose. And there is -- there are predictions in terms of where one will see that. And we have the predefined conditions that we would say would warrant going into expansion in those indications that we have selected. As and when we initiate those expansions in the indication-specific expansions, we can let you guys know why we selected them. But in essence, some of the things that we were thinking about was what's the probability of success here? We want strong proof of concept out of these escalations, but we also want a path to a BLA filing. So when we consider our knowledge of the biology, what's happening in some of the competitor programs, and also considering regulatory path and risk/reward from a financial perspective, there were some of the things that come into the discussion when we were identifying the most high priority indications to go for once we have expansion.

至於我們從升級到擴張的速度，正如史蒂夫指出的那樣，有一個劑量範圍，正如您從競爭性計劃中知道的那樣，我們在這裡尋找的是最佳生物劑量。並且有一些關於人們會在哪裡看到這一點的預測。我們有預先定義的條件，我們認為這些條件可以保證在我們選擇的那些適應症中擴張。當我們在特定於指示的擴充中啟動這些擴充時，我們可以讓你們知道我們選擇它們的原因。但本質上，我們考慮的一些事情是這裡成功的可能性有多大？我們希望從這些升級中獲得強而有力的概念證明，但我們也希望獲得 BLA 備案的途徑。因此，當我們考慮我們的生物學知識、一些競爭對手項目中發生的情況，並從財務角度考慮監管路徑和風險/回報時，當我們確定最重要的項目時，會討論一些事情。一旦我們進行擴張，就需要採取高優先級的指示。

Thanks for that, Shane. I guess just one question on 060. Completed enrollment in the 10 mg cohort. Has the safety follow-up been completed yet on those? Just kind of wondering if we can check the box on that safety being okay at the 10 mg level.

謝謝你，謝恩。我想只有一個關於 060 的問題。已完成 10 毫克隊列的登記。那些的安全後續工作已經完成了嗎？只是想知道我們是否可以勾選 10 毫克的安全性。

Well, remember, it's a blinded study, and there is -- after enrollment, there is the treatment period and then there's follow-up. So it will go through the same thorough review that we put the 1 mg and the 3 mg cohorts through. So we would expect that as we had had an announcement of passing the safety gate for the 1 mg and the 3 mg cohorts earlier this year, we would expect to do a similar review and analysis and announcement in due course. But that still has to get through the dosing and the follow-ups. So although we will not be moving the 10 mg cohort into the efficacy phase, having that 10 mg safety data will be very valuable because it will -- one, it will confirm if we pass the gate, it will confirm the drug is safe at quite high doses. And number two, really relevantly, it will allow flexibility beyond Phase IIa to dose beyond 3 mg if we want to do that for whatever reason. So I would say stay tuned. There's a process and an unblinding process and assessment. And I would expect that we would do the same thing that we did with the 1 mg and 3 mg for the 10 mg.

好吧，請記住，這是一項盲法研究，入組後，有治療期，然後是追蹤期。因此，它將經歷與我們對 1 毫克和 3 毫克組相同的徹底審查。因此，我們預計，正如今年早些時候我們宣布通過 1 毫克和 3 毫克組的安全門一樣，我們預計會在適當的時候進行類似的審查、分析和公告。但這仍然需要透過給藥和後續行動。因此，儘管我們不會將 10 毫克隊列進入療效階段，但擁有 10 毫克安全性數據將非常有價值，因為它會——第一，它將確認我們是否通過了大門，它將確認該藥物在相當高的劑量。第二，真正相關的是，如果我們出於任何原因想要這樣做，它將允許 IIa 期之後的劑量超過 3 毫克的靈活性。所以我想說請繼續關注。有一個過程，一個非盲過程和評估。我預計我們會對 10 毫克的藥物做與 1 毫克和 3 毫克相同的事情。

Our next question comes from Roger Song with Jefferies.

我們的下一個問題來自 Jefferies 的 Roger Song。

Great. Congrats for all the progress. A few quick ones for 060. One is since the protocol amendment by AstraZeneca, so can you just provide some color around the enrollment improvements? And particularly as we see the COVID still living with us, but people start to wearing masks less and less. And do you start to see normal people for the efficacy portion, or it's kind of gradually kind of changed over time? Maybe last quick one, just a follow-up. I think, Steve, you mentioned 10 mg is for the safety. You're not going to do this for the Phase Ia for efficacy. But is that possible -- just confirm, is that possible for you to go up to 10 mg in Phase IIb or Phase III later? If that's the case, what kind of a signal you need for you to make that decision?

偉大的。祝賀所有的進步。 060 的一些快速資訊。其中之一是自阿斯特捷利康 (AstraZeneca) 修訂方案以來，您能否提供一些有關註冊改進的資訊？尤其是當我們看到新冠病毒仍然與我們共存，但人們開始越來越少戴口罩時。您是否開始看到正常人的功效部分，或隨著時間的推移逐漸改變？也許是最後一個快速的，只是一個後續。我想，史蒂夫，你提到 10 毫克是為了安全。您不會為了療效而在 Ia 期中這樣做。但這有可能嗎？只要確認一下，你們是否有可能在 IIb 期或之後的 III 期將劑量提高到 10 毫克？如果是這樣的話，你需要什麼樣的訊號才能做出決定？

Great. Thanks, Roger. So your first question was around enrollment trends, and then the second one was, again, what -- how the 10 mg and other factors could -- safety data from the 10 mg and other factors could inform what we would do beyond Phase IIa beyond the 3 mg dose. For the first question on enrollment, I would say we're not going to break out specific enrollment numbers. We haven't done that, and we're not going to be able to do that. However, I would say there are probably 3 factors that would impact enrollment rates. You mentioned one is just the broader environment. If masks are coming off more and if people get back to more of a normal lifestyle, if that then presents opportunities for more viral exposure challenges, would that just drive up incidence and make the throughput overall throughput higher. So that's one factor to consider. Second one is just more site engagement. And that's one that will I think, per se, help to improve enrollment rates. And the third point, which I think is the most meaningful, is the impact of the amendments. Remember, we said we were going to be broadening the funnel. We don't have to go into all the details. We talked about them pretty thoroughly last quarter. But we do believe that those amendments will squarely address a lot of the reasons for screen failures in the early parts of the study. And as those filings have been made, and a number of those filings have been through the review process and been accepted, they're now just being implemented. So it's too early to be able to predict accurately how much they will bend the curve. But I would say that given -- that getting back to normal more and more on the lifestyle, the additional site engagement that AZ is committed to be doing, and then the implementation of the amendments over the next couple of months, that collectively gives us a good deal of hope and reason to believe that we will move the enrollment up meaningfully. And we just need more time to be able to assess that. And then, of course, we would provide an update in due course whenever we have more visibility on that.

偉大的。謝謝，羅傑。所以你的第一個問題是關於入組趨勢，然後第二個問題又是，10 毫克和其他因素如何——來自 10 毫克和其他因素的安全性數據可以告訴我們在 IIa 期之後會做什麼3毫克劑量。對於關於入學的第一個問題，我想說我們不會透露具體的入學人數。我們還沒有這樣做，我們也不可能這樣做。然而，我想說可能有 3 個因素會影響入學率。你提到的一個只是更廣泛的環境。如果口罩脫落得更多，如果人們更多地恢復正常的生活方式，如果這帶來了更多病毒暴露挑戰的機會，這是否會增加發病率並使整體吞吐量更高。所以這是需要考慮的因素之一。第二個是更多的網站參與度。我認為這本身就有助於提高入學率。第三點，也是我認為最有意義的一點，就是修正案的影響。請記住，我們說過我們將擴大管道。我們不必討論所有細節。上個季度我們非常徹底地討論了它們。但我們確實相信，這些修正案將直接解決研究早期部分螢幕故障的許多原因。隨著這些文件的提交，其中一些文件已經通過審查程序並被接受，它們現在才剛開始實施。因此，現在準確預測它們將使曲線彎曲多少還為時過早。但我想說的是，鑑於生活方式越來越恢復正常，AZ 致力於增加網站參與度，然後在接下來的幾個月內實施修正案，這共同為我們提供了幫助我們充滿希望，也有理由相信我們將有意義地提高入學率。我們只是需要更多時間來評估這一點。當然，只要我們對此有更多了解，我們就會在適當的時候提供更新。

On the second question around the 10 mg, what would we do with that going forward, the 10 mg safety data. I think the way we would look at it is, one, we wanted to have confirmed safety at the 10 mg cohort. And so that will go through its process, as I mentioned in my answer to Matt's question. And then I think it's going to come down to, in particular, the efficacy readout. We've talked about what the bogey should be for efficacy in terms of FEV1 against placebo, and we think being better than the border of what's clinically relevant would be really useful. And if it's better than that, then that's going to be very good. And depending on how much we think we could and want to push the dose beyond 3 mg to potentially improve efficacy even more, that, coupled with the safety assessment, would be 2 important factors that would govern that decision. So we have to be data driven. We have to then first confirm that the 10 mg dose is safe. But I think that we will have enough parameters to be able to make an intelligent decision with AstraZeneca on if we want to go higher than 3 mg and what that would be. It doesn't have to go 3 mg to 10 mg. It could be something in between, of course. And that's something that we would, again, opine on before we go forward in co-development.

關於 10 毫克的第二個問題，我們將如何處理 10 毫克的安全資料。我認為我們看待這個問題的方式是，第一，我們希望確認 10 毫克隊列的安全性。正如我在回答馬特問題時提到的，這將經歷它的過程。然後我認為這將具體歸結為功效讀數。我們已經討論了 FEV1 相對於安慰劑的功效的禁忌應該是什麼，我們認為優於臨床相關的邊界將是非常有用的。如果比這更好，那就太好了。根據我們認為可以並且希望將劑量推至 3 毫克以上以進一步提高療效的程度，再加上安全性評估，這將是決定這一決定的兩個重要因素。所以我們必須以數據為驅動。然後我們必須先確認 10 毫克劑量是安全的。但我認為，我們將有足夠的參數，能夠與阿斯特捷利康一起做出明智的決定，決定是否要高於 3 毫克以及該劑量是多少。不必從 3 毫克到 10 毫克。當然，也可能介於兩者之間。在我們繼續共同開發之前，我們會再次對此發表意見。

Awesome. Maybe just very quick one for the cash runway, given you have a lot of collaboration, the potential milestone payments. So just curious, before this early 2024 cash runway, do you expect you will have meaningful milestone to extend the cash runway?

驚人的。考慮到你們有很多合作，可能只是非常快的現金跑道，潛在的里程碑付款。所以我很好奇，在 2024 年初的現金跑道之前，您是否預計會有有意義的里程碑來延長現金跑道？

I'll turn that one over to Tom, Roger.

我會把這個交給湯姆，羅傑。

Yes. So Roger, we talked in our cash runway, we do include some of the near-term milestones that we have increasing confidence and visibility into in some of our partnered assets that we've talked about on the call today. So those are included. I think just in context, though, they're nice to have. They're certainly probably more modest than some of the AZ-type milestones we've recorded in the past. So just for clarity, these are modest and meaningful to us. They help the cash balance. But they're not quite at that AZ level for that because it was a later stage asset that we were putting into the clinic at that time.

是的。羅傑，我們在現金跑道上談到了一些近期里程碑，我們對我們今天在電話會議上討論的一些合作資產的信心和可見度不斷增強。所以這些都包括在內。不過，我認為就上下文而言，擁有它們還是很高興的。它們肯定可能比我們過去記錄的一些 AZ 型里程碑更為溫和。因此，為了清楚起見，這些對我們來說是適度且有意義的。他們有助於現金平衡。但他們還沒有完全達到 AZ 水平，因為這是我們當時投入臨床的後期資產。

Got it. Thank you for confirming that.

知道了。感謝您確認這一點。

And it looks like that was our final question. I'll turn it back over to Stephen Yoder for closing remarks.

看起來這是我們的最後一個問題。我將把它轉回給史蒂芬·尤德（Stephen Yoder）做結束語。

Thank you, gentlemen. I just want to thank everyone again for your attention today, and thank you for your continued support of Pieris. Thanks, everyone. Have a great day.

謝謝你們，先生們。我只是想再次感謝大家今天的關注，並感謝大家對Pieris的持續支持。感謝大家。祝你有美好的一天。

Thank you. This concludes today's conference call. We thank you for your participation. You may disconnect your lines at this time, and have a great day.

謝謝。今天的電話會議到此結束。我們感謝您的參與。此時您可以斷開線路，祝您有個愉快的一天。