Palvella Therapeutics Inc (PVLA) 2022 Q4 法說會逐字稿

Hello, and welcome to the Pieris Pharmaceuticals, Inc. Year-End 2022 Conference Call and Webcast. (Operator Instructions) As a reminder, this conference is being recorded.

您好，歡迎參加 Pieris Pharmaceuticals, Inc. 2022 年年終電話會議和網路廣播。 （操作員指示）謹此提醒，本次會議正在錄製中。

It's now my pleasure to turn the call over to Tom Bures. Please go ahead, sir.

現在我很高興將電話轉給湯姆布雷斯。請繼續，先生。

Thanks, Kevin. Good morning, everyone, and thank you for joining us for our year-end 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; Shane Olwill, our Chief Development Officer; and Mary Fitzgerald, Vice President, Project Leader for elarekibep, who will be available for Q&A. You can access the press release issued this morning on the Investor Relations page of our website at www.pieris.com.

謝謝，凱文。大家早安，感謝您參加我們的 2022 年底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； Shane Olwill，我們的首席開發長； elarekibep 副總裁兼專案負責人 Mary Fitzgerald 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 obligations 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。

I will now turn the call over to Steve.

我現在將把電話轉給史蒂夫。

Well, thank you, Tom, and thank you to everyone for joining us today for our year-end 2022 earnings call. Today, I will be providing an update on how we have continued to advance multiple clinical and preclinical programs that carry transformative potential while also remaining committed to cost-effective operations. I also will provide progress updates on the company's top priority, obtaining data from the elarekibep Phase IIa study in asthma.

好吧，謝謝你，湯姆，也謝謝大家今天參加我們的 2022 年底財報電話會議。今天，我將提供有關我們如何繼續推進多個具有變革潛力的臨床和臨床前項目的最新信息，同時仍然致力於具有成本效益的運營。我還將提供公司首要任務的最新進展，即從 elarekibep IIa 期氣喘研究中獲取數據。

Elarekibep is an oral inhaled IL-4 receptor alpha antagonist, also referred to as PRS-060 or AZD1402, which is partnered with AstraZeneca.

Elarekibep 是一種口服吸入型 IL-4 受體 α 拮抗劑，也稱為 PRS-060 或 AZD1402，與阿斯特捷利康合作。

Further, I will provide an update on the additional clinical and preclinical inhaled respiratory programs Pieris is advancing alongside elarekibep as we seek to build a leading respiratory pipeline. Respiratory diseases such as asthma, idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease are areas of significant unmet need, and these are also indications that continue to be dramatically underserved by the biopharmaceutical industry. If we are successful advancing inhaled biologics that directly target the relevant lung tissue, we expect to offer a fundamentally new approach to treating multiple, high-prevalence respiratory diseases, potentially transforming how patients with these diseases are treated.

此外，我將提供有關 Pieris 與 elarekibep 一起推進的其他臨床和臨床前吸入呼吸計劃的最新信息，因為我們尋求建立領先的呼吸管道。氣喘、特發性肺纖維化和慢性阻塞性肺病等呼吸系統疾病是嚴重未滿足需求的領域，而這些也是生物製藥產業仍嚴重缺乏服務的適應症。如果我們成功地開發出直接針對相關肺組織的吸入生物製劑，我們期望能夠提供一種全新的方法來治療多種高發呼吸系統疾病，從而有可能改變這些疾病患者的治療方式。

Turning to our respiratory pipeline in more detail, I will begin with elarekibep. We are working closely with our collaborator, AstraZeneca or AZ, who is enrolling the ongoing Phase IIa study for asthma as the study sponsor. We believe elarekibep could represent an expansive opportunity as an inhaled biologic for asthma that has the potential to address important shortcomings of currently approved drugs. The underlying biology targeted by elarekibep is well characterized, and we believe that the development path for this program has also been meaningfully derisked.

更詳細地討論我們的呼吸管道，我將從elarekibep開始。我們正在與我們的合作者阿斯特捷利康 (AstraZeneca) 或 AZ 密切合作，後者作為研究申辦者正在招募正在進行的氣喘 IIa 期研究。我們相信elarekibep作為一種治療氣喘的吸入生物製劑可能代表著廣闊的機會，有可能解決目前核准的藥物的重要缺點。 elarekibep 所針對的基礎生物學已得到很好的表徵，我們相信該專案的開發路徑也已有意義地降低了風險。

Elarekibep targets IL-4 receptor alpha, as mentioned, a target validated by dupilumab, which is an FDA-approved inhibitor of IL-4 receptor alpha that has demonstrated pheno reduction and clinical efficacy in uncontrolled moderate to severe asthma. The elarekibep commercial opportunity is substantial when considering the current multibillion-dollar asthma therapeutics market. By directly targeting lung tissue through a convenient route of administration, elarekibep has the ability to provide a superior product profile, offering a route of administration that many patients and health care providers would prefer.

如前所述，Elarekibep 的靶點是IL-4 受體α，這是經過dupilumab 驗證的靶點，dupilumab 是FDA 批准的IL-4 受體α 抑制劑，已在不受控制的中度至重度在氣喘中證明了表型減少和臨床療效。考慮到當前價值數十億美元的氣喘治療市場，elarekibep 的商業機會是巨大的。透過便捷的給藥途徑直接針對肺組織，elarekibep 能夠提供卓越的產品特性，提供許多患者和醫療保健提供者更喜歡的給藥途徑。

If we are successful, we believe that elarekibep could transform how asthma is managed and the result in commercial opportunity would be substantial. Further, we believe positive data from elarekibep would validate our broader respiratory franchise. In addition, there may be future opportunities to develop elarekibep in indications beyond asthma. Notably, recently reported positive dupilumab Phase III data in COPD provide clear clinical evidence that an IL-4 receptor alpha antagonist can help COPD patients with type 2 inflammation. It is our view that an inhaled IL-4 receptor alpha intervention could be as relevant to treat COPD as it is for asthma.

如果我們成功，我們相信 elarekibep 可以改變氣喘的治療方式，並帶來巨大的商業機會。此外，我們相信來自 elarekibep 的積極數據將驗證我們更廣泛的呼吸特許經營權。此外，未來可能有機會開發elarekibep用於氣喘以外的適應症。值得注意的是，最近報告的 Dupilumab 在 COPD 中的陽性 III 期數據提供了明確的臨床證據，表明 IL-4 受體 α 拮抗劑可以幫助患有 2 型發炎的 COPD 患者。我們認為，吸入 IL-4 受體 α 介入對於治療慢性阻塞性肺病可能與治療氣喘一樣重要。

Now turning to the details of the current clinical study. The elarekibep Phase IIa trial is well powered and intended to provide clear evidence of the clinical promise of elarekibep in moderate to severe uncontrolled asthma. From an efficacy perspective, the study will compare patients administered ICS/LABA background therapy plus 3 milligrams of DPI, or dry powder inhaled, formulated elarekibep versus patients administered as ICS/LABA background therapy plus placebo. The study's primary efficacy endpoint will evaluate FEV1 improvement at 4 weeks relative to placebo. The top line results will also include an overview of the 1-milligram, 3-milligram and 10-milligram DPI dose cohorts in the safety portion of this study.

現在轉向目前臨床研究的細節。 elarekibep IIa 期試驗效果良好，旨在提供明確的證據，證明 elarekibep 在中度至重度不受控制的氣喘的臨床前景。從療效角度來看，研究將比較接受 ICS/LABA 背景治療加 3 毫克 DPI（或吸入乾粉、配製的 elarekibep）的患者與接受 ICS/LABA 背景治療加安慰劑的患者。研究的主要療效終點將評估 4 週時 FEV1 相對於安慰劑的改善。最重要的結果還將包括本研究安全部分中 1 毫克、3 毫克和 10 毫克 DPI 劑量組的概述。

Based on our recent discussions with AstraZeneca, top line Phase IIa study results from this study are now expected to be reported by the middle of 2024. AstraZeneca continues as the operational lead, and this change from prior guidance is based on their most recent assessment of the study as well as updated projections based on AstraZeneca's actions taken to deliver this study.

根據我們最近與阿斯特捷利康的討論，這項研究的主要 IIa 期研究結果預計將於 2024 年中期報告。阿斯特捷利康繼續擔任營運領導者，與先前指導的這一變化是基於他們最近的評估該研究以及基於阿斯特捷利康為進行該研究而採取的行動的更新預測。

As a baseline, we are pleased that AstraZeneca has received regulatory approval in all jurisdictions for a previously announced protocol amendment. As a reminder, this amendment was prepared to improve recruitment while maintaining study rigor. The protocol changes include expanding FEV1 inclusion from 60% to 80% to 50% to 85%; permitting high-dose inhaled corticosteroids and long-acting beta agonist ICS/LABA combinations as background therapy, where previously this was limited to moderate dose ICS/LABA. In addition, there was simplification of the schedule of assessments and other modifications intended to reduce unnecessary patient and site burdens.

作為基線，我們很高興阿斯特捷利康先前宣布的協議修正案已獲得所有司法管轄區的監管批准。提醒一下，這項修正案是為了在保持研究嚴謹性的同時改善招募。協議變更包括將 FEV1 包含範圍從 60% 至 80% 擴大至 50% 至 85%；允許高劑量吸入性皮質類固醇和長效β受體激動劑ICS/LABA組合作為背景治療，而先前僅限於中等劑量的ICS/LABA。此外，也簡化了評估時間表和其他修改，旨在減少不必要的患者和現場負擔。

Moreover, AZ has communicated to us that elarekibep is a high-priority program and that their organization is significantly increasing operational resources on the study to drive patient recruitment, including the addition of several new countries and sites, bringing the total number of clinical sites in this study to over 100.

此外，AZ 也告知我們，elarekibep 是一個高度優先的項目，他們的組織正在大幅增加該研究的營運資源，以推動患者招募，包括增加幾個新的國家和地點，從而使臨床地點總數達到這項研究超過100個。

While it remains too early to fully appreciate the impact of these study changes, leading indicators such as clinical site engagement and patient screening data are encouraging. With elarekibep being strongly supported by AstraZeneca's organizational commitment and with the increased resources provided, we are eagerly looking forward to obtaining study results. This important data set, alongside the delivery of a development plan and budget from AstraZeneca, will trigger our opt-in decision into co-development. Being in a position to opt-in if data are positive is a top priority for our company, and you will hear in a few moments from Tom how we are prudently managing our finances with elarekibep as our highest priority.

雖然現在要充分認識這些研究變化的影響還為時過早，但臨床中心參與度和患者篩檢數據等領先指標令人鼓舞。由於elarekibep得到了阿斯特捷利康組織承諾的大力支持以及所提供的資源的增加，我們熱切期待獲得研究結果。這一重要的數據集，以及阿斯特捷利康提供的開發計劃和預算，將觸發我們選擇共同開發的決定。如果資料呈陽性，則能夠選擇加入是我們公司的首要任務，稍後您將聽到 Tom 講述我們如何以 elarekibep 作為我們的最高優先事項來謹慎管理我們的財務。

Before this, however, I want to spend some time discussing 2 other highly differentiated inhaled respiratory programs that we are advancing, PRS-220 and PRS-400, both of which are fully proprietary. Given the data we have generated so far with elarekibep, we have increased conviction in the validity and differentiation of our inhaled therapeutic protein approach.

然而，在此之前，我想花一些時間討論我們正在推進的另外 2 個高度差異化的吸入呼吸項目，PRS-220 和 PRS-400，這兩個項目都是完全專有的。鑑於迄今為止我們透過 elarekibep 獲得的數據，我們對吸入治療蛋白方法的有效性和差異性更加確信。

PRS-220 is an inhaled Anticalin protein with best-in-class potential that targets connective tissue growth factor, or CTGF, for the treatment of idiopathic pulmonary fibrosis in other forms of fibrotic lung disease. Preclinically, PRS-220 has demonstrated superior on-target potency compared to pamrevlumab, which is an intravenously infused CTGF antagonist in late-stage clinical development. Critically, we believe that an inhaled route of administration provides for superior lungs exposure and may lead to a superior clinical outcome compared to a systemically administered approach in this pathway.

PRS-220 是一種吸入式 Anticalin 蛋白，具有同類最佳潛力，以結締組織生長因子 (CTGF) 為靶點，用於治療其他形式的纖維化肺病中的特發性肺纖維化。在臨床前，PRS-220 與 pamrevlumab 相比已表現出優越的標靶效力，pamrevlumab 是一種處於臨床開發後期的靜脈注射 CTGF 拮抗劑。至關重要的是，我們認為，與該途徑中的全身給藥方法相比，吸入給藥途徑提供了更好的肺部暴露，並可能導致更好的臨床結果。

Based on these potential benefits, the convenience of at-home delivery via inhalation as well as the ability to combine PRS-220 with current standard of care for IPF, we believe PRS-220 could have best-in-class potential for this serious disease. We continue to administer PRS-220 according to plan to subjects in a Phase I single ascending dose and multi-ascending dose study that is evaluating the safety, tolerability and pharmacokinetics in healthy volunteers. We expect to report study results in the second half of this year. As a reminder, this work is partially funded by a grant from the Bavarian Ministry of Economic Affairs Regional Development and Energy.

基於這些潛在的好處、透過吸入在家分娩的便利性以及將 PRS-220 與當前 IPF 護理標準相結合的能力，我們相信 PRS-220 對於這種嚴重疾病可能具有同類最佳的潛力。我們繼續按計劃對 I 期單劑量遞增和多劑量遞增研究中的受試者施用 PRS-220，該研究正在評估健康志願者的安全性、耐受性和藥物動力學。我們預計將在今年下半年報告研究結果。提醒一下，這項工作的部分資金來自巴伐利亞經濟事務部區域發展和能源部的撥款。

Lastly, I want to provide an update on PRS-400, which is an inhaled anti-Jagget-1 antagonist being developed for the treatment of muco-obstructive lung disease. Our enthusiasm for this program is based on the large market opportunity represented by mucus-driven respiratory diseases and is supported by preclinical data showing that PRS-400 can regulate mucus production in the lung.

最後，我想提供有關 PRS-400 的最新信息，它是一種吸入式抗 Jagget-1 拮抗劑，正在開發用於治療黏液阻塞性肺病。我們對該計劃的熱情基於以粘液驅動的呼吸系統疾病為代表的巨大市場機會，並得到了臨床前數據的支持，表明 PRS-400 可以調節肺部粘液的產生。

Furthermore, given the desire to avoid disrupting mucus homeostasis throughout the body, especially in the intestines, we believe an inhaled intervention is the most appropriate route of administration to address muco-obstructive lung disease. PRS-400 is designed to block the JAG1 notch signaling locally in the lung via oral inhalation with the objective of reversing Goblet Cell metaplasia, hyperplasia and mucus plugging as well as increasing the number of ciliated cells. Unlike many other interventions that aim to reduce mucus burden, PRS-400's mode of action is independent of stimulus, which we believe offers applicability across a broader patient population.

此外，考慮到避免破壞全身性黏液穩態的願望，特別是在腸道中，我們認為吸入乾預是解決黏液阻塞性肺部疾病的最合適的給藥途徑。 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。與許多其他旨在減少黏液負擔的干預措施不同，PRS-400 的作用模式獨立於刺激，我們相信這適用於更廣泛的患者群體。

Our team has made excellent progress optimizing and further characterizing PRS-400 program lead candidates, and we anticipate presenting additional preclinical data throughout 2023 and we are also working towards a development candidate nomination later this year.

我們的團隊在優化和進一步表徵 PRS-400 項目主要候選藥物方面取得了巨大進展，我們預計在 2023 年全年提供更多臨床前數據，並且我們還在努力在今年稍後提名開發候選藥物。

Turning now briefly to our immuno-oncology pipeline. We remain committed to delivering on our partnered obligations, and I want to highlight that with the benefit of our existing collaborators, our immuno-oncology pipeline is being advanced in a cost-efficient manner. We also believe that multiple opportunities exist to generate value from this portfolio based on promising preclinical and clinical data, and we continue to work to achieve this objective.

現在簡單介紹一下我們的免疫腫瘤學管道。我們仍然致力於履行我們的合作義務，我想強調的是，在我們現有合作者的幫助下，我們的免疫腫瘤學管道正在以具有成本效益的方式推進。我們也相信，基於有前景的臨床前和臨床數據，存在多種機會從該產品組合中創造價值，我們將繼續努力實現這一目標。

For example, in our collaboration agreement with Servier, we continue enrollment in the dose escalation portion of the Phase I/II study of PRS-344 or S095012, which is a 4-1BB PD-L1 Mabcalin bispecific for the treatment of solid tumors.

例如，在我們與施維雅的合作協議中，我們繼續參與PRS-344 或S095012 的I/II 期研究的劑量遞增部分，這是一種用於治療實體瘤的4-1BB PD-L1 Mabcalin 雙特異性藥物。

Next, within our Seagen collaboration, we earned a $5 million milestone payment when they initiated a Phase I study for SGN-BB228 also known as PRS-346, which is a first-in-class CD228 4-1BB bispecific antibody Anticalin compound designed to provide a potent co-stimulatory bridge between tumor-specific T cells and CD228-expressing tumor cells. Beyond this program, Pieris is committed to delivering on 2 other programs with Seagen. We believe -- we received full reimbursement for internal and external spending on these programs.

接下來，在我們與Seagen 的合作中，當他們啟動SGN-BB228（也稱為PRS-346）的I 期研究時，我們獲得了500 萬美元的里程碑付款，SGN-BB228 是一種一流的CD228 4-1BB 雙特異性抗體Anticalin 化合物，旨在在腫瘤特異性 T 細胞和表達 CD228 的腫瘤細胞之間提供有效的共刺激橋樑。除了該計劃之外，Pieris 還致力於與 Seagen 合作實施另外 2 個計劃。我們相信——我們收到了這些項目的內部和外部支出的全額報銷。

Finally, I want to mention that Boston Pharmaceuticals continues to advance PRS-342 or BOS-342, which is a 4-1BB GPC3 bispecific Mabcalin compound towards the clinic with Phase I expected to begin in the coming months. We are eligible to receive a more nominal milestone payment upon the first in-human dosing on this program, and we believe that clinical entry of this program, which would be the fourth clinical stage 4-1BB bispecific from our IO franchise offers additional long-term upside.

最後，我想提一下，波士頓製藥公司繼續將 PRS-342 或 BOS-342（一種 4-1BB GPC3 雙特異性 Mabcalin 化合物）推向臨床，第一階段預計將在未來幾個月開始。我們有資格在該計劃的首次人體給藥後獲得更名義上的里程碑付款，並且我們相信該計劃的臨床進入，這將是我們IO 特許經營權中的第四個臨床階段4-1BB 雙特異性藥物，可提供額外的長期-術語上行。

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

我準備好的演講到此結束，現在我將把電話交還給湯姆。

Thank you, Steve. Cash and cash equivalents and investments totaled $59.2 million for the quarter ended December 31, 2022, and this does not include the $5 million Seagen milestone payment which was received in February of 2023.

謝謝你，史蒂夫。截至 2022 年 12 月 31 日的季度，現金及現金等價物及投資總額為 5,920 萬美元，不包括 2023 年 2 月收到的 500 萬美元 Seagen 里程碑付款。

The year-end cash balance is compared to a cash and cash equivalents balance of $117.8 million for the year-ended December 31, 2021, with the overall decrease during the course of 2022 being a result of the need to fund operations. The company believes operations are sufficiently funded for more than the next 12 months.

與截至 2021 年 12 月 31 日止年度的現金和現金等價物餘額 1.178 億美元相比，年終現金餘額在 2022 年期間總體減少，這是由於需要為營運提供資金。該公司相信，未來 12 個月的營運資金充足。

Research and development expenses were $53 million for the year-ended December 31, 2022, compared to $66.7 million for the year-ended December 31, 2021. This decrease is due to the lower overall program costs for both elarekibep and cinrebafusp alfa as well as due to lower manufacturing costs across other late-stage respiratory and immuno-oncology programs, lower license fees and lower consulting costs. These lower costs were partially offset by higher clinical costs for PRS-220 and PRS-344 or S095012. Higher preclinical spending was also incurred on PRS-400, and there's an increase in personnel and travel costs.

截至2022年12月31日止年度的研發費用為5,300萬美元，而截至2021年12月31日止年度的研發費用為6,670萬美元。這一減少是由於elarekibep和cinrebafusp alfa以及由於其他後期呼吸系統和免疫腫瘤學課程的製造成本較低、許可費和諮詢成本較低。這些較低的成本被 PRS-220 和 PRS-344 或 S095012 較高的臨床成本部分抵消。 PRS-400 的臨床前支出也較高，人員和差旅費用也增加。

Next, general and administrative costs were $16.4 million for the year-ended December 31, 2022, compared to $16.6 million for the year-ended December 31, 2021. The period-over-period decrease was driven primarily by lower personnel facilities and audit and tax costs, partially offset by higher business development, travel and amortization of deferred costs related to revenue recognition.

其次，截至 2022 年 12 月 31 日止年度的一般及行政費用為 1,640 萬美元，而截至 2021 年 12 月 31 日止年度為 1,660 萬美元。同比下降的主要原因是人事設施和審計及稅收成本，部分被較高的業務發展、差旅和與收入確認相關的遞延成本攤銷所抵銷。

Moving on to other income. For the year-ended December 31, 2022, $8.2 million of grant income was recorded with respect to PRS-220 compared to $3.7 million for the year-ended December 31, 2021. The increase is due to higher overall costs incurred on PRS-220 as the program progressed into Phase I clinical studies along with a full year of grant funding eligibility in 2022 compared to 2021, the year in which the grant was awarded.

轉向其他收入。截至2022 年12 月31 日止年度，PRS-220 記錄了820 萬美元的補助收入，而截至2021 年12 月31 日止年度的補助金收入為370 萬美元。這一增長是由於PRS-220 產生的整體成本較高與授予補助金的 2021 年相比，該計畫已進入 I 期臨床研究，並在 2022 年獲得全年補助金資助資格。

The company's net loss was $33 million -- $33.3 million or a $0.45 loss per share for the year-ended December 31, 2022, compared to a net loss of $45.7 million or $0.71 loss per share for the year-ended December 31, 2021.

截至2022年12月31日止年度，該公司的淨虧損為3,300萬美元，即3,330萬美元或每股虧損0.45美元，而截至2021年12月31日止年度的淨虧損為4,570萬美元或每股虧損0.71美元。

With respect to my remarks that we believe operations are sufficiently funded for more than the next 12 months, I wanted to make a few additional comments. First, we believe in the immense commercial potential of our respiratory programs and that inhaled biologics can yield transformative therapies not possible by other modalities. We remain committed to our mission and are evaluating opportunities to support the long-term development of therapeutic candidates such as PRS-220 and PRS-400.

關於我的言論，即我們認為未來 12 個月以上的營運資金充足，我想發表一些額外的評論。首先，我們相信我們的呼吸系統計畫具有巨大的商業潛力，吸入生物製劑可以產生其他方式無法實現的變革性療法。我們仍然致力於我們的使命，並正在評估支持 PRS-220 和 PRS-400 等治療候選藥物長期開發的機會。

However, we cannot ignore the more constrained environment in which we are operating and we continue to reduce our cost profile, as evidenced by the significantly reduced cash burn of approximately $22 million in the second half of 2022 compared to more than $40 million in the first half while having meaningfully advanced our 2 proprietary respiratory programs PRS-220 and PRS-400.

然而，我們不能忽視我們的營運環境更加受限，我們將繼續降低成本，2022 年下半年的現金消耗大幅減少約 2,200 萬美元，而上半年的現金消耗則超過 4,000 萬美元。一半，同時有意義地推進了我們的2 個專有呼吸計畫PRS-220 和PRS-400。

Although our operating plans for the current year include the benefit of cost saving actions we have already taken, we are prepared to gate future investments on PRS-220 and PRS-400, including certain Phase II readiness activities for PRS-220 and IND-enabling activities for PRS-400 in the interest of achieving our top priority, namely obtaining data from the elarekibep Phase IIa study in asthma.

儘管我們今年的營運計劃包括我們已經採取的成本節約行動的好處，但我們準備好控制 PRS-220 和 PRS-400 的未來投資，包括 PRS-220 和 IND 啟用的某些第二階段準備活動PRS- 400 的活動是為了實現我們的首要任務，即從elarekibep IIa 期氣喘研究中獲取數據。

Based on the current time lines for AZ to deliver this study, we are confident we will be able to achieve our cash reach objective on the basis of our current balance sheet, making cost saving decisions as needed and being supported by anticipated modest milestones from existing collaborations.

根據 AZ 提供這項研究的當前時間表，我們相信我們將能夠在當前資產負債表的基礎上實現我們的現金目標，根據需要做出成本節約決策，並得到現有預期適度里程碑的支持合作。

With that, I'll now hand the call back over to Steve.

這樣，我現在將把電話轉回給史蒂夫。

Thank you, Tom, and thank you all for joining us on the call today. We would now like to open the call for any questions.

謝謝湯姆，也謝謝大家今天加入我們的電話會議。我們現在想打開電話詢問任何問題。

(Operator Instructions) Our first question today is coming from Roger Song from Jefferies.

（操作員說明）今天我們的第一個問題來自 Jefferies 的 Roger Song。

Great. Thanks for the update and taking our questions. Just a couple from us. The first one for 060, knowing the time line projection is mostly driven by AstraZeneca, but just do you know any kind of -- I think, Steve, you mentioned on the call some leading indicators, the enrollment is accelerating after the protocol amendment and opening new sites. Can you just give us a little bit more color around this acceleration of the enrollment and how confident maybe you and AstraZeneca about the new time line for the top line data in mid-2024.

偉大的。感謝您的更新並回答我們的問題。只有我們幾個人。第一個是060，知道時間線預測主要是由​​阿斯特捷利康推動的，但你知道嗎——我想，史蒂夫，你在電話會議上提到了一些領先指標，在協議修訂後，註冊人數正在加速，並且開設新網站。您能否就註冊人數的加速向我們提供更多信息，以及您和阿斯特捷利康對 2024 年中期營收數據的新時間線有多大信心？

Sure, Roger. Thanks for the question. Understood. Look, PRS-060 has been challenging to enroll, as we mentioned. However, we're very encouraged by the composite of efforts that AZ has been doing and has really increased resource commitments, as we've communicated, hopefully, clearly today. There has been a composite of meaningful protocol amendments that squarely address a significant portion of previously observed screen failures and those have been fully approved in all the jurisdictions we mentioned.

當然，羅傑。謝謝你的提問。明白了。看，正如我們所提到的，註冊 PRS-060 一直很困難。然而，我們對 AZ 一直在做的綜合努力感到非常鼓舞，並且確實增加了資源承諾，正如我們今天所明確傳達的那樣。已經出現了一系列有意義的協議修正案，這些修正案直接解決了先前觀察到的螢幕故障的很大一部分，並且這些修正案已在我們提到的所有司法管轄區中得到充分批准。

There has been meaningful additional site engagement, which has translated into some of the increase in, for example, screening, which we can come back to. And very importantly, there has been this clear increase in operational commitments to increase both geographies by more than 50% of the current number of geographies that are listed on ct.gov and a significant increase of sites to over more than 100.

網站的參與度也增加了，這很有意義，這也轉化為一些增加，例如篩選，我們可以回過頭來討論。非常重要的是，營運承諾明顯增加，將兩個地區的數量增加到目前 ct.gov 上列出的地區數量的 50% 以上，並將站點數量大幅增加到 100 多個。

So when we combine the more ease in enrollment, the increased site engagement and the significant volume of increased sites, we believe that, that is all trending in the direction that we need it to go. And I think there's -- without question, -- nope, there is no question that AZ doesn't believe this is a very high priority, and they are treating it as a very high priority.

因此，當我們將更輕鬆的註冊、增加的網站參與度以及大量增加的網站結合起來時，我們相信，這一切都朝著我們需要的方向發展。我認為——毫無疑問，——不，毫無疑問，AZ 不認為這是一個非常高的優先級，而且他們將其視為非常高的優先級。

I think what is also very helpful is as we've been working through COVID and we're working through post-COVID, we are operating under a new normal for enrolling asthma studies. And we, with every passing month, every passing quarter, are getting more real-time visibility on the throughput of patients through sites on studies such as PRS-060. And so we will continue to rely on real-time intelligence from the global CRO that's administering the study for AZ to be as accurately informed as possible on those recruitment rates. And that is something that we have factored into our go-forward projections for delivering the study by the middle of 2024.

我認為也非常有幫助的是，由於我們一直在努力應對新冠疫情以及後疫情時期的工作，因此我們正在按照新常態進行氣喘研究的招募工作。我們每個月、每季都透過 PRS-060 等研究網站獲得更多關於患者吞吐量的即時可見性。因此，我們將繼續依賴負責管理 AZ 研究的全球 CRO 的即時情報，盡可能準確地了解這些招募率。我們已將這一點納入 2024 年中期進行研究的前瞻性預測中。

There is, I think, some important nuances or other aspects of the study we can remind on in terms of the path to getting patients ultimately randomized, they are not maybe hand it over to Mary Fitzgerald, who can go through the actual sequence of events and why the screenings, we believe, are a reliable leading indicator to ultimately increasing the enrollment and delivering the study on plan. So Mary, do you want to take that one?

我認為，就讓患者最終隨機化的路徑而言，我們可以提醒研究的一些重要細微差別或其他方面，他們可能不會將其交給可以經歷實際事件順序的瑪麗·菲茨杰拉德以及為什麼我們相信篩檢是最終增加入學率和按計劃進行研究的可靠領先指標。瑪麗，你想買那個嗎？

Thank you, Steve. Yes, Roger, one of the things that happened is that screening takes some time to translate into actual randomization. So we have a 2-week screening period followed by a 4-week run-in period. So there is 6 weeks then between the initial screening and when patients can be randomized. So there is always a lag behind an increase in screening and the randomization. So we expect based on the approval of the new protocol with these amendments that will enhance screening will take a little bit of time to come into place that based on this 6-week period before patients are randomized.

謝謝你，史蒂夫。是的，羅傑，發生的事情之一是篩選需要一些時間才能轉化為實際的隨機化。因此，我們有 2 週的篩選期，然後是 4 週的磨合期。因此，從初次篩選到對患者進行隨機分組之間有 6 週的時間。因此，篩檢和隨機化的增加總是存在滯後。因此，我們預計，基於新方案的批准以及這些將加強篩檢的修正案，根據患者隨機分組前的 6 週時間，需要一些時間才能落實到位。

That's great. Yes, thanks for all the comments. I think we have a better understanding of the improvement here. Okay, so maybe just another question related to 060, also the cash runway, given the time line, it's kind of working towards your cash for the top line, understanding you're gating your other earlier pipeline to prioritize the 060. But just to remind us what will be the next step for 060 after top line. What will happen there? And how does that build into your operational plan?

那太棒了。是的，感謝所有的評論。我想我們對這裡的改進有了更好的理解。好吧，也許只是與 060 相關的另一個問題，也是現金跑道，考慮到時間線，這有點為您的現金收入而努力，了解您正在關閉其他早期管道以優先考慮 060。但只是為了提醒我們060在頂線之後的下一步是什麼。那裡會發生什麼事？這如何納入您的營運計劃？

So Roger, I'll just say at a high level a couple of remarks and turn it over to Tom. So we are considering that the current cash reach will allow us to get through the data, the 060 elarekibep top line data. And that is absolutely a priority. It's prio 1, it's something we are extremely committed to getting through on the basis of our balance sheet and, as we mentioned, modest anticipated milestones from our existing collaborations.

羅傑，我將簡單說幾句話，然後將其轉交給湯姆。因此，我們正在考慮目前的現金範圍將使我們能夠獲取數據，即 060 elarekibep 頂線數據。這絕對是一個優先事項。這是首要任務，我們非常致力於在我們的資產負債表的基礎上完成這項任務，正如我們所提到的，我們現有合作的適度預期里程碑。

The mechanics of co-development are pretty clear. And we also believe it's going to be a watershed moment for that program leading to clinical validation, and we would be prepared to manage financing a co-development opt-in at that time. Tom can talk again about the specific mechanics of what triggers our co-development opt-in and what we will have at the time, both internally and externally, to communicate publicly at the time we would communicate our opt-in decision.

共同開發的機制非常清楚。我們也相信，這將是該計劃走向臨床驗證的分水嶺，屆時我們將準備好為共同開發選擇提供融資。湯姆可以再次談論觸發我們共同開發選擇加入的具體機制，以及我們在傳達選擇加入決定時將在內部和外部進行公開溝通的具體機制。

Yes. Thanks. And right, so we have -- at the time of the top line data readout, right, AstraZeneca would also need to give us a development plan -- going-forward development plan that they would prepare in asthma, the indication of asthma, for this program to get to BLA filing. With those 2 pieces of information, we have to make our co-development opt-in decision.

是的。謝謝。是的，所以我們——在頂線數據讀出時，阿斯特捷利康還需要給我們一個開發計劃——他們將在哮喘、哮喘的適應症方面準備的未來開發計劃，該程序可用於 BLA 備案。有了這兩個訊息，我們必須做出共同開發的決定。

The opt-in, we can, at 2 levels, one at 25% with a cost share, with a cost cap. And the other is a 50% without a cost cap. In either one of those scenarios, the benefit compared to not opting in, for example, is that we get an increased share of economics for the lifetime of the program as opposed to a defined royalty -- defined term or period if we don't opt-in. so enhanced economics on the back end.

我們可以選擇加入，分為 2 個級別，第一個級別為 25%，並具有成本分攤和成本上限。另一種是 50%，沒有成本上限。例如，在這兩種情況中的任何一種情況下，與不選擇加入相比，好處是我們在計劃的整個生命週期中獲得了更大的經濟份額，而不是確定的特許權使用費——如果我們不選擇，則確定的期限或期限選擇參加。因此增強了後端的經濟性。

And when we think about the opt-in overall, again, I think one of the pieces that we think is very manageable for us, again regardless of our profile, is at the time of the readout, assuming the data is good, the opt-in at 25% at a minimum is something that we will achieve or have an offset of future development milestones on this program that cover about 50% of the overall opt-in cost that we would have with AstraZeneca. So that becomes a very attractive option for us on this program. And it's, again, we think about the -- again, like the multibillion-dollar opportunity in asthma and the market brings not even to mention the potential for COPD or other respiratory indications, right, again, we see the pathway that dupilumab has forged and this, again, creates a great opportunity for us, and so we very much value the co-development opt-in decisions that we have.

當我們再次考慮整體選擇加入時，我認為我們認為對我們來說非常容易管理的部分之一（無論我們的個人資料如何）是在讀出時，假設數據良好，選擇加入- 至少25% 是我們將實現的目標，或抵銷該計劃的未來發展里程碑，該計劃涵蓋了我們與阿斯特捷利康的整體選擇成本的約50%。因此，這對我們這個計劃來說是一個非常有吸引力的選擇。我們再次想到，就像氣喘領域帶來的數十億美元的機會，市場帶來的甚至更不用說慢性阻塞性肺病或其他呼吸系統疾病的潛力，對，我們再次看到 dupilumab 已經形成的途徑這再次為我們創造了一個絕佳的機會，因此我們非常重視我們所做的共同開發選擇決定。

Thank you. Your next question is coming from Jonathan Miller from Evercore ISI.

謝謝。您的下一個問題來自 Evercore ISI 的 Jonathan Miller。

Just to follow on, on Roger's question there. Am I understanding right that the current cash milestone, you no longer anticipate -- the current cash flow you no longer anticipate to be sufficient to fund that 25% opt-in on its own and you have to finance that when the time comes?

繼續，關於羅傑的問題。我的理解是否正確，即當前的現金里程碑，您不再預期 - 當前的現金流量您不再預期足以單獨為 25% 選擇加入提供資金，而您必須在時機成熟時為其提供資金？

And then just related to that, when you say you're prepared to gate for the development for 220 and 400 in the interest of 060 advancement, can you give us some color around the time lines, how those time lines might change as we wait and when you would know whether or not you can move forward with those development programs in advance of the 060 readout.

與此相關的是，當你說你準備為了 060 的進步而準備 220 和 400 的開發時，你能給我們一些關於時間線的信息嗎？在我們等待的過程中，這些時間線可能會如何變化以及您何時知道是否可以在060 讀數之前推進這些開發計劃。

Sure. Thanks, Jon. On the first question, just to be clear that, yes, we are not factoring our runway the ability to opt-in on the back of positive clinical efficacy data for PRS-060 or elarekibep, but we've never factored that in. So again, we believe that, that data set will be a watershed moment for the program. And given the time line for that data set to be delivered and all of the other optionality within our pipeline and our history of transacting with third parties to create significant shareholder value, we remain very optimistic and confident that we will be able to manage through that at the appropriate time.

當然。謝謝，喬恩。關於第一個問題，需要明確的是，是的，我們並沒有將我們的跑道選擇加入 PRS-060 或 elarekibep 的積極臨床療效數據的能力考慮在內，但我們從未考慮過這一點。我們再次相信，該數據集將成為該計劃的分水嶺。考慮到該資料集的交付時間表以及我們管道中的所有其他可選性，以及我們與第三方進行交易以創造重大股東價值的歷史，我們仍然非常樂觀和有信心，我們將能夠管理好這一問題在適當的時間。

The second question was around gating expenses. Well, I would say at a high level, and I'll turn it over to Tom, that we believe we still have time to manage those critical path activities, to look at multiple options that we're working on across our pipeline. And as you could imagine, PRS-400, more early stage, is a lower cost investment relative to PRS-220. However, PRS-220 is going to continue to benefit heavily from Bavarian grant through the Phase I study, and we are absolutely committed to completing the Phase I study which is on plan.

第二個問題是關於門禁費用。好吧，我想說的是，我會將其轉交給湯姆，我們相信我們仍然有時間管理這些關鍵路徑活動，以研究我們正在整個管道中研究的多個選項。正如您可以想像的那樣，PRS-400 處於更早階段，相對於 PRS-220 來說是成本更低的投資。然而，PRS-220 將透過第一階段研究繼續從巴伐利亞撥款中受益匪淺，我們絕對致力於完成計劃中的第一階段研究。

There will be some Phase II readiness activities that we will need to consider later in the year, second half of the year, and that's probably all we can say about that. But again, we have time to work through a lot of different options, including what we think could be a very informative readout from FibroGen's pamrevlumab, which has been communicated by FibroGen as something that would be disclosed by the middle of this year. So I think that's another important piece. Nonetheless, we do believe PRS-220 has already demonstrated best-in-class potential based on the preclinical data we've seen and also based on the fundamental biology where we believe you absolutely should interrogate this locally to have a meaningful clinical benefit.

我們將需要在今年稍後、下半年考慮一些第二階段的準備活動，這可能是我們能說的全部。但同樣，我們有時間研究許多不同的選擇，包括我們認為可能是 FibroGen 的 pamrevlumab 的資訊非常豐富的讀數，FibroGen 已將其傳達為將於今年年中披露的內容。所以我認為這是另一個重要的部分。儘管如此，我們確實相信 PRS-220 已經根據我們所看到的臨床前數據以及基礎生物學表現出了一流的潛力，我們相信您絕對應該在本地進行研究以獲得有意義的臨床益處。

Yes. And maybe I'll just add one thing in terms of the overall spending. I'd say this doesn't change for those 2 programs the path that we're on today. It just is going to impact the going forward later this year, as Steve mentioned, right, and how quickly we're able to continue to move those programs along. For example, we know a Phase II study for PRS-220 is something we would have to independently work to fund. So certainly, some Phase II readiness-type activities and starting that would make sense, again, in terms of gating that type of spending in order to make sure that we have sufficient runway to achieve the readout for elarekibep.

是的。也許我會在整體支出方面添加一件事。我想說這不會改變這兩個項目我們今天所走的道路。正如史蒂夫所提到的，這只會影響今年稍後的進展，以及我們能夠以多快的速度繼續推進這些計劃。例如，我們知道 PRS-220 的 II 期研究需要我們獨立工作來資助。因此，當然，一些第二階段準備型活動和開始是有意義的，再次，在控制此類支出方面，以確保我們有足夠的跑道來實現 elarekibep 的讀數。

And it's the same thing with PRS-400, sort of. There's a lot of costs that come into play once you get to a development candidate nomination that you're going to have to incur for CMC and (inaudible) work to bring that to an IND state. So those are the type of costs that -- those programs continue. It's just those larger expenditures, some of those cannot be incurred or committed to in the near term.

PRS-400 也是如此。一旦獲得開發候選者提名，您將需要承擔 CMC 和（聽不清楚）工作以將其納入 IND 狀態，從而產生大量成本。這些就是這些計劃持續存在的成本類型。只是那些較大的支出，其中一些在短期內無法發生或承諾。

Makes sense. Makes sense. And then on the oncology side of the business. Obviously, most of this is off your balance sheet and is being done through existing collaboration agreements, which is great. I guess I'd love to get a sense for your expectation on milestone potential -- funding potential there. Is your cash crunch in any way going to impact the potential for those programs to develop with the collaborators?

說得通。說得通。然後是腫瘤學方面的業務。顯然，其中大部分都在您的資產負債表之外，並且是透過現有的合作協議完成的，這很棒。我想我很想了解您對里程碑潛力（那裡的融資潛力）的期望。您的現金短缺是否會影響與合作者共同開發這些項目的潛力？

So Jon, Steve here. I would answer that by saying we continue to increase the ratio of investments on respiratory to IO, as you probably imagine. And our current IO investments are very measured. Going forward, we're predicting that, that's probably going to be about 10% of, for example, cash on hand. So that's something that's very manageable, given, as you said, we have most of this development expenditure for IO off of our balance sheet.

喬恩、史蒂夫在這裡。我的回答是，正如您可能想像的那樣，我們將繼續增加呼吸與 IO 的投資比例。我們目前的IO投資是非常謹慎的。展望未來，我們預測，這可能會占到手頭現金的 10% 左右。因此，這是非常容易管理的，正如您所說，我們的 IO 開發支出大部分都在資產負債表之外。

For 344, escalation is ongoing and we would expect to disclose those data publicly before changing the spend ratio that I mentioned. And we believe that given all of the data we've generated and the commitment of the several partners that have now (inaudible) 4 bispecifics in the clinic based on the same format in 4-1BB biology that there will be opportunities to get a net positive outcome for Pieris. And we believe that and we're going to -- we just have to let some of those things play out.

對於 344，升級正在進行中，我們希望在更改我提到的支出比率之前公開披露這些數據。我們相信，鑑於我們產生的所有數據以及目前在臨床中擁有（聽不清楚）4 個基於 4-1BB 生物學相同格式的雙特異性抗體的幾個合作夥伴的承諾，將有機會獲得網絡皮埃里斯的積極成果。我們相信這一點，並且我們將擁有——我們只需讓其中一些事情發生即可。

Thank you. Next question is coming from Matt Phipps from William Blair.

謝謝。下一個問題來自威廉布萊爾的馬特菲普斯。

This is Rob Andrew on from Matt Phipps here. One of the issues that was raised last year was screen failures, and it's kind of been touched on a little bit here, but you've made efforts to kind of widen the funnel to avoid some of those failures. So I guess can you just confirm that you are now seeing less screening failures following the implementation of those protocol changes?

我是馬特·菲普斯的羅布·安德魯。去年提出的問題之一是螢幕故障，這裡稍微涉及了一點，但你們已經努力擴大管道以避免其中一些故障。所以我想您能否確認，在實施這些協議變更後，您現在看到的篩檢失敗次數減少了？

And then, Steve, I think you mentioned 100 sites now. Looks from clinical trials (inaudible) life, there's about 60 up and running with about 40 listed as active. Could you just give us a sense of how up to date that is and what the time lines are for getting to that 100 site number?

然後，史蒂夫，我想你現在提到了 100 個網站。從臨床試驗（聽不清楚）來看，大約有 60 個正在運行，其中大約 40 個被列為活躍。您能否讓我們了解一下該資訊的最新情況以及達到第 100 個站點編號的時間安排？

Sure, Rob. Happy to talk about that. Yes, your first question was on the screen failures and how much the amendments have impacted that. And then the second question was on the how current is the list on ct.gov. I think Mary closely working with AZ can talk specifically about those. We've already mentioned the impact of the -- that the amendments have -- were meant to address about 50% of the screen failures and that the T2 endotype is -- will also continue to be a basis or has been a basis for screening failures, but we do not want to compromise on that point.

當然，羅布。很高興談論這個。是的，您的第一個問題是關於螢幕故障以及修正案對其產生了多大影響。第二個問題是關於 ct.gov 上的名單的最新情況。我認為與 AZ 密切合作的 Mary 可以具體談論這些。我們已經提到了修正案的影響 - 旨在解決約 50% 的篩檢失敗問題，並且 T2 內型 - 也將繼續作為或一直是篩檢的基礎失敗，但我們不想在這一點上妥協。

Again, remember, the composite of eosinophil and pheno cutoffs, I think, really put us in the bull's eye of the right patient population. So that's something we really want to try to maintain, and we are. And we do believe with the significant increase in volume of additional sites and geographies that we're able to address that and manage that going forward.

再次記住，我認為，嗜酸性粒細胞和表型截止值的組合確實使我們成為了正確患者群體的目標心。所以這是我們真正想要努力維持的事情，而我們確實做到了。我們確實相信，隨著其他站點和地區數量的顯著增加，我們能夠解決這個問題並在未來進行管理。

But Mary, please feel free to talk a bit about the nature of those amendments and how it's addressed a critical amount of the screening failures and then also the trajectory, at a high level, of the onboarding of the additional sites to get over 100 sites as we mentioned.

但是，瑪麗，請隨意談談這些修正案的性質，以及它如何解決大量篩選失敗的問題，以及在較高層面上增加其他網站以獲得超過 100 個網站的軌跡正如我們所提到的。

Yes, of course. Yes, okay. Matt, in terms of the screening failures, some of the things that have been implemented, I mean I think you're aware of them that the widening of the FEV1, for example, they allowing high dose inhaled corticosteroids, allowing separate devices to be used for the ICS and LABA combination, all of these significantly contribute to improving the screen failure rate. So that goes down.

是的當然。是的，好的。馬特，就篩檢失敗而言，已經實施的一些措施，我的意思是，我認為您已經意識到 FEV1 的擴大，例如，它們允許高劑量吸入皮質類固醇，允許單獨的設備用於ICS和LABA組合，所有這些都顯著有助於提高螢幕故障率。這樣就下降了。

But as Steve says, we can't reduce screen failure rate to 0 and everyone would anticipate that you will still see screen failures due to ensuring we have a T2 endotype in the study, and, of course, that's the appropriate endotype for the FEV1 improvement that we're looking for.

但正如 Steve 所說，我們無法將螢幕故障率降低到 0，並且每個人都會預期您仍然會看到螢幕故障，因為確保我們在研究中具有 T2 內型，當然，這是 FEV1 的適當內型我們正在尋找的改進。

So I think we've done what we can here. And obviously, we're in constant dialogue with the site to try and make sure that we accommodate things that are difficult to the site. So we have simplified, if you like, the assessments being done at each visit. So all of these contributes making the study easier for patients and for sites. So all of these things, we think, will contribute to more patients coming into the study.

所以我認為我們已經盡力了。顯然，我們一直在與網站進行對話，以確保我們能夠適應網站遇到的困難。因此，如果您願意的話，我們簡化了每次訪問時進行的評估。因此，所有這些都有助於使患者和研究中心的研究變得更加容易。因此，我們認為所有這些都將有助於更多的患者參與研究。

And you alluded to the 60 sites that are being currently listed on clinicaltrial.gov, which is accurate. There's -- AZ have a transparency policy, whereby they put meaningful changes on clinicaltrials.gov on a regular basis. So I wouldn't expect the numbers there to be out of cost -- it's what's actually happening.

您提到了 ClinicalTrial.gov 目前列出的 60 個網站，這是準確的。 AZ 制定了透明度政策，根據該政策，他們會定期在 ClinicalTrials.gov 上進行有意義的更改。所以我不認為那裡的數字會超出成本——這就是實際發生的情況。

But when you make the decision to include new countries and new sites, of course, there's a lag between the time it takes between agreeing that you're going to do that but missing the protocols, the new protocol, to those countries to be approved and those countries being approved and then the site being activated and screening starting. So we wouldn't expect to see a significant increase there until later in the year when the countries approve the protocol and the sites that are involved in the study. So we would expect to see that happening towards the mid-half of the year, so Q2, Q3. So that's just, unfortunately, how long it takes to get countries involved and then site active. I hope that answers your question.

但是，當您決定納入新國家/地區和新網站時，當然，從同意您要這樣做但錯過協議、新協議到這些國家/地區獲得批准之間存在一段時間差這些國家獲得批准，然後網站被激活並開始篩選。因此，直到今年晚些時候，當各國批准該協議和參與研究的站點時，我們預計才會顯著增加。因此，我們預期這種情況會在今年中期發生，也就是第二季、第三季。不幸的是，這就是讓各國參與然後網站活躍起來需要多長時間。我希望這能回答你的問題。

Yes. That's helpful. Just one other question. The dupilumab success in COPD was mentioned in the call. Could you just kind of remind us the connection -- what decision to pursue an additional indication would be kind of as it relates to the original deal and opt-ins or additional indications treated separately when it comes to those kind of decisions, if there were a decision to pursue any additional indications such as COPD.

是的。這很有幫助。還有一個問題。電話會議中提到了 dupilumab 在治療慢性阻塞性肺病 (COPD) 方面的成功。您能否提醒我們這種聯繫——追求額外指示的決定會是什麼樣的，因為它與原始交易和選擇加入有關，或者在涉及此類決定時單獨處理的額外指示（如果有）決定尋求任何其他適應症，如慢性阻塞性肺病。

Thanks, Rob. And yes, so we are -- as I mentioned, we are enthusiastic about the dupilumab data, as in the past other so-called T2 intervention, say, on IL-5 5 receptor have not produced such robust results. So we do believe that this continues to validate IL-4Ra as the quintessential intervention point for T2 asthma, in particular, stratifying as we continue to stratify patients.

謝謝，羅布。是的，正如我所提到的，我們對 dupilumab 數據充滿熱情，因為過去其他所謂的 T2 幹預（例如針對 IL-5 5 受體）並未產生如此強勁的結果。因此，我們確實相信，這繼續驗證了 IL-4Ra 作為 T2 氣喘的典型幹預點，特別是隨著我們繼續對患者進行分層，IL-4Ra 也得到了分層。

And as it relates to the co-development opt-in, we do believe there are multiple features of the co-development option that actually facilitate peers being able to participate in significant upside or additional indications that makes sense for oral administration, including COPD. Tom can talk about some of those mechanics, but some of the components that would allow us to participate should we choose to opt-in, even if the time of the opt-in, it's not clear exactly when additional indications may be pursued.

由於它與共同開發選擇相關，我們確實相信共同開發選擇有多個特徵，實際上可以促進同行能夠參與對口服給藥有意義的重大優勢或其他適應症，包括慢性阻塞性肺病。湯姆可以談論其中一些機制，但如果我們選擇選擇加入，一些允許我們參與的組件，即使選擇加入的時間，也不清楚何時可以尋求額外的指示。

So with that, I'll turn it over to Tom for some more of those details.

因此，我會將其交給 Tom 以獲取更多詳細資訊。

Sure. Yes. As it relates to an indication like COPD, for example, the development plan that AstraZeneca could give us, I think that is something we'll have to talk with them about whether they would go right after COPD right now. So lots of discussions to still yet happen. But it would be clear, or it is very clear, that the development opt-in decision is for the indication of asthma. So that's the primary indication.

當然。是的。因為它涉及像慢性阻塞性肺病這樣的適應症，例如阿斯特捷利康可以給我們的開發計劃，我認為我們必須與他們討論他們是否會立即在慢性阻塞性肺病之後進行。因此，仍有大量討論發生。但很明顯，或者說非常明顯的是，開發選擇決定是針對氣喘的適應症。這就是主要跡象。

However, any opt-in decision that we take, whether it be, again, say, do nothing, the 25% or the 50%, the resulting economics apply for all future indications. So if we're opting in, for example, at a 50% level and we're going to get a gross margin share, that will apply to all indications because there's no way to split whether it's going to be asthma or COPD or other indications in the future. So the economic upside for AZ's decision to expand to other indications is going to be very clear in terms of what the economic benefit would be.

然而，我們所做的任何選擇加入的決定，無論是不採取任何行動、25% 還是 50%，所產生的經濟學結果都適用於所有未來的跡象。因此，如果我們選擇，例如，在 50% 的水平上，我們將獲得毛利率份額，這將適用於所有適應症，因為沒有辦法區分它是氣喘、慢性阻塞性肺病還是其他疾病。未來的跡象。因此，就經濟效益而言，AZ 決定擴展到其他適應症的經濟優勢將非常明顯。

From a cost perspective, overall, the development plans in terms of what they give us initially, that sort of comprises the biggest piece of our -- sort of known commitment. There are mechanisms in the contract by which these additional costs or obligations to us for that development pattern would come into play, and we know we're going to have those obligations. But some of it could be part of, again, like an ongoing budget, or some of it could be deferred until later in terms of the overall contract time line. So it's a little bit more nuanced in terms of how the cost obligation comes in. But I guess I would say that's helpful in terms of we know we get the economics and then it's just a little bit more how we pay for that.

從成本的角度來看，總的來說，開發計劃就他們最初給我們的東西而言，這構成了我們已知的承諾中最大的一部分。合約中存在一些機制，透過這些機制，我們針對該開發模式的額外成本或義務將發揮作用，並且我們知道我們將承擔這些義務。但其中一些可能再次成為持續預算的一部分，或者其中一些可能會根據總體合約時間表推遲到稍後。因此，就成本義務的產生方式而言，這有點微妙。但我想我會說，這很有幫助，因為我們知道我們獲得了經濟效益，然後我們為此支付的方式就多了一點。

Thanks, Tom. And I would just sum up to say we would welcome additional investment in other indications as a co-development partner along with AstraZeneca, alongside AstraZeneca. We would not meet any such ambitions with fear or trepidation, it would be manageable -- manageable investments based on mechanics of the contract in our view, which would allow significant growth for the program, which allows significant economic upside for Pieris.

謝謝，湯姆。我想說的是，我們歡迎作為與阿斯特捷利康共同開發的合作夥伴，在其他適應症方面進行額外投資。我們不會帶著恐懼或惶恐來實現任何這樣的雄心壯志，它是可控的——我們認為，基於合約機制的可控投資，這將使該計劃顯著增長，從而為皮里斯帶來顯著的經濟上行空間。

We reached the end of our question-and-answer session, I'd like to turn the floor back over to Steve for any further or closing comments.

我們的問答環節已經結束，我想將發言權交還給史蒂夫，以徵求進一步的意見或結束意見。

Okay. Well, thank you, Kevin. And I want to thank everyone again today for your attention and for your continued support of the company. We are truly excited by the promise in particular of our inhaled biologics pipeline and the opportunity to improve outcomes for patients with respiratory disease. We look forward to updating you on our progress. Have a great day.

好的。嗯，謝謝你，凱文。今天我要再次感謝大家的關注以及對公司的持續支持。我們對吸入生物製劑管道的前景以及改善呼吸系統疾病患者治療結果的機會感到非常興奮。我們期待向您通報我們的最新進展。祝你有美好的一天。

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.

謝謝。今天的電話會議和網路廣播到此結束。此時您可以斷開線路，度過美好的一天。我們感謝您今天的參與。