Palvella Therapeutics Inc (PVLA) 2021 Q2 法說會逐字稿

Greetings, and welcome to the Pieris Pharmaceuticals' Second Quarter Earnings Conference Call. (Operator Instructions) As a reminder, this conference is being recorded.

您好，歡迎參加 Pieris Pharmaceuticals 第二季財報電話會議。 （操作員指示）謹此提醒，本次會議正在錄製中。

It is now my pleasure to introduce your host, Tom Bures, Vice President, Finance. Thank you. You may begin.

現在我很高興向您介紹主持人，財務副總裁 Tom Bures。謝謝。你可以開始了。

Good morning, everyone, and thank you for joining us for our second quarter 2021 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. We also have on the line Tim Demuth, our Chief Medical Officer, who joined us just this week who will introduce himself later in the call. You can access the press release released this morning on the Investor Relations page of our website at www.pieris.com.

大家早安，感謝您參加我們的 2021 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。我們的首席醫療官 Tim Demuth 也在電話中，他本週剛加入我們，稍後他將在電話中介紹自己。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, 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、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有重大差異。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。

Thank you, Tom, and thank you to everyone for joining us today for our 2021 second quarter earnings call. I want to begin by extending a warm welcome to Dr. Tim Demuth, who Tom just noted, joined as our Chief Medical Officer and who comes with deep clinical development experience. While Tim understandably will be in listening mode for the Q&A session during this call, he will provide some prepared remarks before Q&A on what attracted him to Pieris. I also want to congratulate Shane, whom all of you know, on his recent appointment as Chief Development Officer. Tim, Shane and Hitto Kaufmann, our Chief Scientific Officer, also on the call today, who has been doing a terrific job driving our innovative Anticalin platform in the past 2 years, they are the perfect complements in our quest to be able and position novel therapeutic proteins that translate great science into transformative medicines for patients.

謝謝湯姆，也謝謝大家今天參加我們的 2021 年第二季財報電話會議。首先，我要熱烈歡迎 Tim Demuth 博士，Tom 剛才提到他加入我們，擔任我們的首席醫療官，他擁有豐富的臨床開發經驗。可以理解的是，蒂姆在本次電話會議期間將處於問答環節的聆聽模式，但他將在問答之前提供一些準備好的評論，說明 Pieris 吸引他的原因。我還要祝賀你們都認識的謝恩最近被任命為首席開發長。 Tim、Shane 和我們的首席科學官Hitto Kaufmann（今天也參加了電話會議）在過去2 年裡一直在推動我們創新的Anticalin 平台方面做出了出色的工作，他們是我們追求創新能力和定位的完美補充治療性蛋白質將偉大的科學轉化為患者的變革性藥物。

Now turning to our accomplishments in the last few months, I'm pleased to update you on the significant progress we have made most notably signing a strategic partnership with industry leader, Genentech, bringing in an additional $20 million as an upfront payment along with more than $1.4 billion in potential milestone payments plus tiered royalties on commercialized programs. We also unveiled our proprietary respiratory program, PRS-220 for idiopathic pulmonary fibrosis or IPF, alongside a $17 million grant from the Bavarian government to evaluate the program in post-COVID pulmonary fibrosis as well.

現在談談我們在過去幾個月中取得的成就，我很高興向您介紹我們所取得的重大進展，最引人注目的是與行業領導者基因泰克(Genentech) 簽署了戰略合作夥伴關係，帶來了2000 萬美元的額外預付款以及更多資金超過 14 億美元的潛在里程碑付款加上商業化項目的分級特許權使用費。我們也推出了用於治療特發性肺纖維化或IPF 的專有呼吸系統計畫PRS-220，以及巴伐利亞政府提供的1700 萬美元撥款，用於評估該計畫在新冠肺炎後肺纖維化方面的情況。

With Genentech, we have a multiprogram research collaboration to discover, develop and commercialize locally delivered respiratory and ophthalmology therapies that leverage our proprietary Anticalin technology. We will be responsible for discovery research and early preclinical development of initial programs, and Genentech will be responsible for IND-enabling activities, clinical development and commercialization of those programs. We now have multiple academic and industry respiratory alliances, and we remain deeply committed to inhaled biologics, which have already shown benefit in the clinic within our AstraZeneca alliance.

我們與基因泰克進行了多專案研究合作，以利用我們專有的 Anticalin 技術來發現、開發和商業化當地提供的呼吸和眼科療法。我們將負責初步計畫的發現研究和早期臨床前開發，基因泰克將負責這些計畫的 IND 支持活動、臨床開發和商業化。我們現在擁有多個學術和行業呼吸聯盟，我們仍然堅定地致力於吸入生物製劑，這些生物製劑已經在我們的阿斯特捷利康聯盟的臨床中顯示出益處。

To partner with a company like Genentech, reinforces we are achieving a high bar on scientific leadership, and we're pleased to do this not only for inhaled biologics, but also another local application, namely ophthalmology via intraocular delivery.

與基因泰克這樣的公司合作，加強了我們在科學領導力方面取得的高標準，我們很高興不僅在吸入生物製劑方面做到這一點，而且在另一種本地應用方面也做到了這一點，即透過眼內輸送進行眼科治療。

I'm also excited to discuss our most recently disclosed proprietary respiratory asset PRS-220, which we unveiled last quarter. PRS-220 is this inhaled Anticalin protein targeting CTGF or connective tissue growth factor for the treatment of IPF. There is a clear unmet need or IPF, which affects 3 million to 5 million people worldwide and about 130,000 people in the U.S. each year. Median survival is 2 to 5 years from the time of diagnosis, and currently approved treatments provide very modest benefit while carrying significant side effects.

我還很高興討論我們最近披露的專有呼吸資產 PRS-220，該資產是我們上季度推出的。 PRS-220是一種吸入性Anticalin蛋白，可針對CTGF或結締組織生長因子，用於治療IPF。有明顯的未滿足需求或 IPF，每年影響全球 300 萬至 500 萬人，以及美國約 13 萬人。從診斷之日起，中位存活期為 2 至 5 年，目前核准的治療方法提供的益處非常有限，但副作用卻很大。

We believe this unmet need can be best addressed through a local inhaled approach, which would allow for targeted delivery directly into the lungs and potentially avoid the systemic side effects seen with current standard of care. CTGF is a clinically validated target with data indicating that inhibition of CTGF reduces the decline in lung function among patients with IPF while being safe and well tolerated, yet there may be limits to treatments that target CTGF systemically. A systemically administered CTGF treatment requires IPF patients who have limited mobility to leave their homes for treatment given via intravenous infusion. An inhaled approach, on the other hand, could be conveniently administered at home.

我們相信，這種未滿足的需求可以透過局部吸入方法得到最好的解決，這種方法可以將藥物直接定向輸送到肺部，並有可能避免目前標準護理中出現的全身副作用。 CTGF 是一個經過臨床驗證的靶點，數據表明，抑制 CTGF 可減少 IPF 患者肺功能的下降，同時安全且耐受性良好，但全身性靶向 CTGF 的治療可能存在局限性。全身性 CTGF 治療要求行動不便的 IPF 患者離開家接受靜脈輸液治療。另一方面，吸入方法可以在家中方便地進行。

Additionally, systemic treatment requires an inefficient high dose, while an inhaled approach would likely be much more efficient. And with PRS-220, we seek to repeat the paradigm of PRS-060 in which we select a validated target that has been shown to work in the clinic via a systemic intervention against the target. And we then create a more efficient inhaled local intervention with the promise of a lower dose, a more convenient administration route and potentially improve therapeutic window. We look forward to presenting initial preclinical data for PRS-220 at this year's European Respiratory Society International Congress on September 5 in a poster presentation.

此外，全身性治療需要低效的高劑量，而吸入方法可能更有效。對於 PRS-220，我們尋求重複 PRS-060 的範式，其中我們選擇一個經過驗證的靶標，該靶標已被證明透過針對標靶的系統幹預在臨床中發揮作用。然後，我們創建一種更有效的吸入局部幹預方法，預計將實現更低的劑量、更方便的給藥途徑，並有可能改善治療窗。我們期待在今年 9 月 5 日舉行的歐洲呼吸學會國際大會上以海報展示的形式展示 PRS-220 的初步臨床前數據。

And also for PRS-220, I want to mention that we received this grant from the State of Bavaria in Germany for approximately $7 million to evaluate the program for post-COVID pulmonary fibrosis. The grant will support clinical readiness activities and initial clinical development for the program, including GLP tox studies, GMP manufacturing and Phase I clinical development. We are planning to initiate clinical development for PRS-220 next year.

對於 PRS-220，我想提一下，我們從德國巴伐利亞州獲得了約 700 萬美元的撥款，用於評估新冠肺炎後肺纖維化計畫。這筆贈款將支持該計畫的臨床準備活動和初步臨床開發，包括 GLP 毒物研究、GMP 製造和 I 期臨床開發。我們計劃明年啟動 PRS-220 的臨床開發。

Moving on to our multi-program AstraZeneca partnership focused on inhaled Anticalin to treat respiratory disease, AstraZeneca continues to enroll in those patients in the first part of the 2-part Phase IIa study of PRS-060 or AZD1402, which is an inhaled DPI formulation, IL-4 receptor alpha inhibitor that we are jointly developing for the treatment of moderate to severe asthma. As a reminder, part 1 of the study is evaluating the safety and the pharmacokinetics of the dry powder formulation of 060 in moderate asthmatics controlled on standard of care, asthma therapy over 4 weeks.

繼續我們的多計畫阿斯特捷利康合作夥伴關係，重點是吸入 Anticalin 治療呼吸道疾病，阿斯特捷利康繼續在 PRS-060 或 AZD1402（一種吸入 DPI 製劑）的 2 部分 IIa 期研究的第一部分中招募這些患者，IL-4受體α抑制劑，我們正在聯合開發用於治療中度至重度氣喘。提醒一下，研究的第 1 部分正在評估 060 乾粉製劑在接受標準護理、氣喘治療超過 4 週的中度氣喘患者中的安全性和藥物動力學。

In Part 2 of the study, whose initiation, we will announce publicly, AstraZeneca will evaluate the efficacy, safety and pharmacokinetics of PRS-060 over 4 weeks in moderate uncontrolled asthmatics having a T2 endotype with the primary endpoint being FEV1 improvement compared to placebo. We are looking forward to announcing the results of this study next year at which time we will have the options to codevelop and separately co-commercialize the drug in the United States. In addition to 060, we have 4 early-stage programs we are working on with AstraZeneca, which continue to advance and about which we will provide updates at an appropriate time.

我們將公開宣布研究的啟動，在該研究的第2 部分中，阿斯特捷利康將在4 週內評估PRS-060 在具有T2 內型的中度未受控制氣喘患者中的療效、安全性和藥物動力學，主要終點是與安慰劑相比FEV1 的改善。我們期待明年宣布這項研究的結果，屆時我們將可以選擇在美國共同開發和單獨共同商業化該藥物。除了060之外，我們還有4個早期項目正在與阿斯特捷利康合作，這些項目將繼續推進，我們將在適當的時候提供最新資訊。

Turning now to our immuno-oncology franchise, I am pleased to report that we are planning to dose the first patient in the Cinrebafusp Alfa Phase II trial in the coming weeks. As a reminder, Cinrebafusp Alfa or CINRA is a 4-1BB HER2 bispecific that we are currently developing for HER2 high and HER2 low gastric cancer. In Phase I studies, the drug showed single agent activity biomarker data supportive of its mechanism of action and an acceptable safety profile. CINRA also showed activity in patients with immunologically cold tumors as well as those with HER2 low-expressing tumors, both of which represent high unmet medical needs. The Phase II study design will involve 2 20 patient arms, 1 with HER2-high patients and 1 with HER2 low patients.

現在談談我們的免疫腫瘤學特許經營權，我很高興地報告，我們計劃在未來幾週內對 Cinrebafusp Alfa II 期試驗的第一位患者進行給藥。提醒一下，Cinrebafusp Alfa 或 CINRA 是一種 4-1BB HER2 雙特異性藥物，我們目前正在開髮用於治療 HER2 高和 HER2 低的胃癌。在第一階段研究中，該藥物顯示出單藥活性生物標記數據支持其作用機制和可接受的安全性。 CINRA 在免疫冷腫瘤患者以及 HER2 低表達腫瘤患者中也表現出活性，這兩種腫瘤都代表著高度未滿足的醫療需求。 II 期研究設計將涉及 2 20 名患者組，其中 1 組為 HER2 高患者，1 組為 HER2 低患者。

The HER2 high arm will evaluate CINRA in combination with the current second-line standard of care regimen, ramucirumab and paclitaxel and is supported by a drug supply agreement with Lilly for ramucirumab. The HER2 low arm will evaluate CINRA in combination with tucatinib TUKYSA, a small molecule inhibitor of HER2 and HER3, and is supported by a drug supply agreement with Seagen. Given the high prevalence of gastric cancer in Asia, we will be enrolling the study in South Korea in addition to the U.S.

HER2 高臂將結合目前的二線標準護理方案、雷莫蘆單抗和紫杉醇來評估 CINRA，並得到與禮來公司簽訂的雷莫蘆單抗藥物供應協議的支持。 HER2 低臂將評估 CINRA 與 HER2 和 HER3 小分子抑制劑 tucatinib TUKYSA 的組合，並得到與 Seagen 的藥物供應協議的支持。鑑於亞洲胃癌發生率較高，除了美國之外，我們還將在韓國進行這項研究。

We will continue to monitor the evolving treatment landscape closely, in particular in the HER2 high landscape and will maintain a high bar for the planned go-no-go analysis of this study in each setting. We will be evaluating a number of efficacy measures, including objective response rate, ORR, duration of response and safety. In the HER2 high arm, we are setting the ORR target at a minimum of 50%; and in the HER2 low arm, we are setting the ORR target at a minimum of 40%. Both targets are higher than the 28% benchmark for ORR established by the standard of care in these settings. We remain confident based on the data we have generated in our Phase I studies that we can achieve these goals.

我們將繼續密切監測不斷變化的治療情況，特別是在 HER2 高水平情況下，並將在每種情況下對本研究計劃進行的不進行分析保持高標準。我們將評估一些療效指標，包括客觀緩解率、ORR、緩解持續時間和安全性。在 HER2 高臂中，我們將 ORR 目標設定為最低 50%；在 HER2 低臂中，我們將 ORR 目標設定為至少 40%。這兩個目標均高於這些環境下護理標準所製定的 28% 的 ORR 基準。根據我們在第一階段研究中產生的數據，我們仍然有信心實現這些目標。

Beyond CINRA is our second most advanced IO asset, PRS-344, or Servier discloses S-095012. PRS-344 is a 4-1BB PD-L1 bispecific we are codeveloping with Servier and where we, Pieris hold full U.S. rights. We are planning to dose the first patient in the Phase I study of PRS-344 this year, and we continue to make great progress towards this goal. This global open-label Phase I dose escalation study will evaluate the safety, tolerability and preliminary evidence of antitumor activity of 344 in patients with advanced solid tumors whose cancer progressed on standard of care treatment. PRS-344 is designed to activate 4-1BB on tumor-specific T cells when bridging to PD-L1 expressing cells within the tumor microenvironment or the draining lymph nodes, and thereby avoid the systemic toxicities previously reported with other 4-1BB bispecifics.

除了 CINRA 之外，我們的第二個最先進的 IO 資產是 PRS-344，或 Servier 揭露的 S-095012。 PRS-344 是一種 4-1BB PD-L1 雙特異性藥物，我們正在與施維雅 (Servier) 共同開發，我們 Pieris 擁有完全的美國權利。我們計劃今年在 PRS-344 的 I 期研究中對第一位患者進行給藥，並且我們將繼續朝著這一目標取得巨大進展。這項全球開放標籤 I 期劑量遞增研究將評估 344 在標準護理治療中癌症進展的晚期實體瘤患者中的安全性、耐受性和抗腫瘤活性的初步證據。 PRS-344 旨在在橋接到腫瘤微環境或引流淋巴結內的PD-L1 表達細胞時激活腫瘤特異性T 細胞上的4-1BB，從而避免先前報道的其他4-1BB 雙特異性藥物的全身毒性。

Given this power, of the IO-IO intervention, several considerations are critical to achieving an optimal therapeutic window. First, PRS-344 has a low nanomolar potency and a several fold reduced affinity for 4-1BB compared to PD-L1, which is important given the bifunctional agonism of 4-1BB versus the antagonism potential of PD-L1 blockade; second, there is a silence IgG4-Fc backbone to avoid undesirable peripheral immune complex formation; Third, it exists by valency on 4-1BB to remain inactive peripherally yet by the potent 4-1BB activation potential when bridging to PD-L1 positive cells, allowing it to avoid disrupting peripheral immune surveillance while driving 4-1BB engagement locally. Overall, we believe this bispecific target combination has already shown some remarkable benefit in clinical development, yet we believe PRS-344 has the potential to improve upon this, and we are looking forward to beginning this study soon.

鑑於 IO-IO 介入的這種力量，有幾個考慮因素對於實現最佳治療窗至關重要。首先，與PD-L1 相比，PRS-344 的納摩爾效力較低，且對4-1BB 的親和力降低數倍，考慮到4-1BB 的雙功能激動作用與PD-L1 阻斷的拮抗潛力，這一點很重要；其次，有一個沉默的 IgG4-Fc 主鏈，以避免不良的周邊免疫複合物形成；第三，它透過4-1BB 上的化合價存在，在外周保持不活躍，但在橋接PD-L1 陽性細胞時通過有效的4-1BB 激活電位，使其能夠避免破壞外周免疫監視，同時驅動4- 1BB 局部參與。總的來說，我們相信這種雙特異性標靶組合已經在臨床開發中顯示出一些顯著的益處，但我們相信 PRS-344 有潛力對此進行改進，我們期待很快開始這項研究。

This concludes my prepared remarks, and I would now like to let Tim introduce himself before I hand the call back over to Tom who will then guide you through our second quarter 2021 financial results. Over to you, Tim.

我準備好的演講到此結束，現在我想讓蒂姆先介紹一下自己，然後再將電話轉給湯姆，然後湯姆將指導您了解我們 2021 年第二季度的財務業績。交給你了，提姆。

Thanks, Steve, and thanks for the warm welcome. Hi, everyone. This is Tim speaking. I'm very thrilled to be joining Pieris. I was drawn to the company for the novelty and vast potential of the Anticalin platform as well as for the individual programs and the promising clinical data the company has already generated. As a physician scientist who spent a lot of his industry career in oncology, I have been particularly intrigued by the immuno-oncology franchise and its 4-1BB-based bispecific focus. I believe there is a tremendous opportunity here for patients, and I am excited about progressing these clinical assets towards approval and bringing some of these earlier assets into clinical trials.

謝謝史蒂夫，也謝謝你熱情的歡迎。大家好。這是蒂姆在講話。我很高興加入 Pieris。我被該公司所吸引，是因為 Anticalin 平台的新穎性和巨大潛力，以及該公司已經產生的個別項目和有前景的臨床數據。作為一名在腫瘤學領域度過了大部分職業生涯的醫師科學家，我對免疫腫瘤學專營權及其基於 4-1BB 的雙特異性焦點特別感興趣。我相信這對患者來說是一個巨大的機會，我很高興能夠推動這些臨床資產獲得批准，並將其中一些早期資產納入臨床試驗。

Beyond immuno-oncology, I'm also very interested in the inhaled application of Anticalin proteins. There's a great need for convenient to administer inhaled respiratory therapies and I believe that Anticalin proteins has shown early promise of offering a solution.

除了免疫腫瘤學之外，我對 Anticalin 蛋白的吸入應用也非常感興趣。人們非常需要方便地進行吸入性呼吸治療，我相信 Anticalin 蛋白已經顯示出提供解決方案的早期前景。

Thank you, everyone, and I look forward to working with the team to advance the pipeline and bring much needed medicines to patients. I would now like to hand over to Tom.

謝謝大家，我期待與團隊合作推動研發管線，為病患帶來急需的藥物。我現在想把事情交給湯姆。

Thank you, Tim, and good morning again, everyone. Cash and cash equivalents totaled $109.1 million for the quarter ended June 30, 2021, compared to a cash and cash equivalent balance of $70.4 million for the year ended December 31, 2020. We have added more than $78 million to our balance sheet in the first half of 2021. Of this increase, $36 million came from existing partners through the achievement of milestones or amending existing agreements. Another $30 million was obtained as upfront payments upon entering new partnerships. And in the second quarter, we raised more than $12 million through targeted use of our ATM facility, selling those shares at an average price of $4.24. The primary use of proceeds continues to be funding the operating needs of the company.

謝謝蒂姆，大家早安。截至2021 年6 月30 日的季度現金和現金等價物總額為1.091 億美元，而截至2020 年12 月31 日的年度現金和現金等價物餘額為7,040 萬美元。第一季度，我們的資產負債表中增加了超過7,800 萬美元。2021 年的一半。其中 3,600 萬美元來自現有合作夥伴，透過實現里程碑或修改現有協議來實現。另外還獲得了 3000 萬美元作為建立新合作夥伴關係時的預付款。在第二季度，我們透過有針對性地使用 ATM 設施籌集了超過 1,200 萬美元，以平均價格為 4.24 美元出售這些股票。所得款項的主要用途仍然是滿足公司的營運需求。

Additionally, our cash balance does not include funds to be received from the Bavarian government grant of approximately $17 million that we announced for our PRS-220 programs. Those funds will be reimbursed over time as program costs are incurred. With this amount of dilutive and non-dilutive funding achieved in the first half of 2021, we are well positioned to execute on our clinical and discovery stage programs into 2023.

此外，我們的現金餘額不包括我們宣布用於 PRS-220 計劃的巴伐利亞政府撥款約 1700 萬美元的資金。這些資金將隨著專案費用的產生而逐漸得到補償。憑藉 2021 年上半年實現的稀釋性和非稀釋性資金數額，我們已做好準備，能夠在 2023 年之前執行我們的臨床和發現階段項目。

R&D expenses were $15.8 million for the quarter ended June 30, 2021, compared to $11.3 million for the quarter ended June 30, 2020. The increase reflects higher spending on preclinical activities for PRS-220, an increase in manufacturing costs across multiple immuno-oncology programs and higher royalty costs associated with entering new collaboration agreements.

截至2021 年6 月30 日的季度研發費用為1,580 萬美元，而截至2020 年6 月30 日的季度研發費用為1,130 萬美元。這一增長反映出PRS-220 臨床前活動支出增加，以及多種免疫腫瘤學製造成本的增加計劃以及與簽訂新的合作協議相關的更高的特許權使用費。

G&A expenses were $4.2 million for the quarter ended June 30, 2021, compared to $4.6 million for the quarter ended June 30, 2020. The decrease reflects lower legal and project management costs in the current quarter, along with higher onetime office and equipment costs incurred related to the move to the new R&D facility in Hallbergmoos, Germany in the prior year. Net loss was $15.5 million or a $0.25 loss per share for the quarter ended June 30, 2021, compared to a net loss of $5 million or a $0.09 loss per share for the quarter ended June 30, 2020.

截至2021 年6 月30 日的季度的一般管理費用為420 萬美元，而截至2020 年6 月30 日的季度的一般管理費用為460 萬美元。這一下降反映了本季法律和專案管理成本的降低，以及產生的一次性辦公室和設備成本的增加與去年搬遷至德國哈爾伯格莫斯的新研發設施有關。截至 2021 年 6 月 30 日的季度淨虧損為 1,550 萬美元，即每股虧損 0.25 美元，而截至 2020 年 6 月 30 日的季度淨虧損為 500 萬美元，即每股虧損 0.09 美元。

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

這樣，我會將電話轉回給史蒂夫。

Thank you, Tom. And before opening it up for Q&A, I just wanted to reiterate that we're really proud of the progress that we have made last quarter, which caps a highly successful first half of the year for us, includes new partnerships; a healthy balance sheet driven by significant non-dilutive capital, as you've heard from Tom; recruitment of top talent, as you heard from Tim; and continued advancement of our pipeline according to plan. Through the course of the second half of this year, we will have 3 actively enrolling clinical stage assets, while planning to enter clinical development with a fourth asset next year. We are capitalized to get beyond key inflection points, including data readouts for our lead respiratory and IO programs next year. And we'll be happy and excited to keep you all informed about our progress along the way.

謝謝你，湯姆。在開始問答之前，我只想重申，我們對上季度取得的進展感到非常自豪，這為我們上半年的成功畫上了圓滿的句號，其中包括新的合作夥伴關係；正如您從湯姆那裡聽到的那樣，由大量非稀釋資本驅動的健康的資產負債表；正如您從蒂姆那裡聽到的那樣，招募頂尖人才；並按計劃繼續推進我們的管道。在今年下半年的過程中，我們將有 3 個資產積極招募臨床階段資產，同時計畫明年以第四個資產進入臨床開發。我們有資本超越關鍵拐點，包括明年我們主要呼吸和 IO 項目的數據讀數。我們將很高興和興奮地讓大家了解我們一路走來的進展。

So thanks for joining today and for listening. And we would now like to open the call for your questions.

感謝您今天的加入與聆聽。現在我們想開始電話詢問您的問題。

(Operator Instructions) Our first question is coming from the line Jonathan Miller with Evercore ISI.

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

I'd like to focus on the new program 220. Looking forward to preclinical data later this year, I think, obviously, we're hoping to see good target coverage with lower delivered doses than systemic competitors, I think you made that clear. But should we be expecting similar doses or formulation strategies will be possible for this as for 060? Or is this sort of a really different regime that isn't comparable? And then secondly, can you talk about the path into the clinic with your 2 indications, 2 proposed indications at this point. How much early work is going to be shared? Will you have to run separate Phase Is in post-COVID fibrosis and in IPF?

我想專注於新專案220。期待今年稍後的臨床前數據，我認為，顯然，我們希望看到比系統競爭對手更低的遞送劑量的良好目標覆蓋範圍，我認為您已經明確表示了這一點。但我們是否應該期待與 060 類似的劑量或配方策略？或者說這是一種完全不同的製度，沒有可比性？其次，您能談談您的 2 個適應症、2 個目前建議的適應症進入診所的路徑嗎？有多少早期工作將被分享？您是否需要在新冠病毒後纖維化和 IPF 中進行單獨的 Is 階段？

Thanks, Jon, for the 2 partners there on 2020. I'll kick it off at a high level, and then Shane can color it on some details. I think each respiratory program actually needs to be considered independently on its own 2 feet. And there are, we think, very notable differences that would be relevant for an inhaled intervention for pulmonary fibrosis compared to asthma ranging from the lung -- compromised lung functions in the different populations as well as the commercial settings today on what patients are accustomed to seed.

謝謝 Jon，2020 年的 2 位合作夥伴。我將從高水平開始，然後 Shane 可以在一些細節上進行著色。我認為每個呼吸方案實際上都需要單獨考慮。我們認為，與氣喘相比，肺纖維化的吸入乾預存在非常顯著的差異——不同人群的肺功能受損，以及當今商業環境對患者習慣的影響。種子。

So whereas we are clearly have our eye on a DPI formulation for an asthma intervention, what we think is better for patient is a nebulized formulation, and that's the path that we're going down. Not because of any limitations on formulability but because we think that's the best way to address the patient population and that would also hold true for long COVID or post-COVID pulmonary fibrosis. And there will be a range of data that we'll touch on drug-like properties, target engagement that you'll see in the poster. And we won't talk about the details beyond that, but that will come out in the first week of September, as we mentioned, in ERS.

因此，雖然我們顯然著眼於用於氣喘幹預的 DPI 製劑，但我們認為對患者更好的是霧化製劑，這就是我們正在走的道路。不是因為配方有任何限制，而是因為我們認為這是解決患者群體問題的最佳方法，對於長期新冠肺炎或新冠肺炎後肺纖維化也同樣適用。我們將涉及一系列關於類藥物特性的數據，您將在海報中看到目標參與。我們不會談論除此之外的細節，但正如我們所提到的，這將在 ERS ​​中於 9 月的第一周公佈。

And then the second point, which is around the clinical path, I would say there are -- there is a high degree of efficiency on the path to the clinic and the early clinical development for this program in both IPF and post-COVID lung fibrosis. We also envision later in the year to put more color on the clinical strategy. So we'll be putting much more detail on it today, but I can say that we're really pleased with the grant in that it is highly leveraged, although we're committed to using the grand for long COVID pulmonary fibrosis, but the funding that gets us into the clinic and into that initial clinical development stage is highly leveraged for everything we want to do for IPF. So we're really enthusiastic about that leverage.

第二點是圍繞臨床路徑，我想說的是，該項目在 IPF 和新冠肺炎後肺纖維化方面的臨床路徑和早期臨床開發都非常高效。 。我們也預計在今年稍後為臨床策略增添更多色彩。因此，我們今天將提供更多詳細信息，但我可以說，我們對這筆贈款感到非常滿意，因為它的槓桿率很高，儘管我們致力於使用這筆資金來治療長期新冠肺纖維化，但讓我們進入臨床並進入初始臨床開發階段的資金對於我們想要為 IPF 所做的一切都具有高度的槓桿作用。因此，我們對這種槓桿作用非常熱衷。

Shane, do you want to cover any other nuances there around the formulation or around the path to and through the initial stages of clinical development, feel free to add any other color?

Shane，您是否想涵蓋有關配方或臨床開發初始階段的任何其他細微差別，請隨意添加任何其他顏色？

Yes. Thanks, Steve, and thanks, Jon, for the question. So just in terms of the learnings or the -- what we can take from PRS-060, certainly, from a formulation perspective and from a delivery perspective, from a dispersion into the lung, and there's a lot we can learn from that. We've got a nice body of preclinical data and of course, clinical data with PRS-060 delivered as a nebulized formulation. So as Steve said, nebulized formulation is where we're heading for PRS-220. So there are understandings there that we can take notwithstanding the fact that we need to generate data with the actual molecule. We have a good understanding of how Anticalins as a drug class behave from a pharmacology perspective in preclinical species, we can use that to simulate a model how we want to go about dosing into the Phase I study. And as Steve said, there's -- from a clinical strategy perspective, we're not going to put a lot of color on it at the moment. But suffice to say, there will be opportunities to explore that PK piece, the dosing piece, the safety piece in a way that's efficient and can be utilized in both indications.

是的。謝謝史蒂夫，也謝謝喬恩提出的問題。因此，就我們可以從 PRS-060 中學到的東西而言，當然，從配方角度、從遞送角度、從分散到肺部的角度來看，我們可以從中學到很多東西。我們擁有大量臨床前數據，當然還有以霧化製劑形式提供的 PRS-060 的臨床數據。正如 Steve 所說，霧化製劑是我們 PRS-220 的發展方向。因此，儘管我們需要用實際分子產生數據，但我們可以採取一些理解。從藥理學角度來看，我們對 Anticalins 作為一類藥物在臨床前物種中的表現有了很好的了解，我們可以用它來模擬我們想要如何在 I 期研究中給藥的模型。正如史蒂夫所說，從臨床策略的角度來看，我們目前不會對此進行過多的渲染。但可以說的是，我們將有機會以有效且可用於兩種適應症的方式探索 PK 部分、劑量部分和安全部分。

Great. Makes sense. Then on the go/no-go bars for 343, I think really glad to see you talking about this pretty explicitly. I think a 50% pay will make sense to a lot of folks, given, as you mentioned, the competitiveness of the high HER2 indication. But -- can you talk a little bit more about the 40% bar in HER2-low patients? As you said, standard of care comps aren't really stratified beyond HER2 positivity usually. So how are you thinking about the right comp for that HER2 low population?

偉大的。說得通。然後在 343 的通過/不通過欄上，我認為很高興看到您非常明確地談論這一點。我認為 50% 的薪酬對許多人來說都是有意義的，正如您所提到的，考慮到 HER2 高適應症的競爭力。但是，您能多談談 HER2 低的患者中 40% 的標準嗎？正如您所說，護理標準通常並沒有真正按照 HER2 陽性進行分層。那麼，您如何考慮 HER2 低人群的合適補償方案？

Well, as you -- I'm happy to again kick this off at a high level and then Shane can feel free to add some color. I think -- as you know, the HER2-high -- classic HER2-high space is much more dynamic and evolving than the HER2-low space. So the standard of care is still ramucirumab paclitaxel with the ORR and the ITT population at about 28%. And there have been a number of examples where targeted HER2 therapies have tried to move into this space, whether it was 2 plus-ish negative or 1 plus. And they kind of hit a wall, and not really showed clinical benefit and sometimes underperformed standard of care or placebo with the trial.

好吧，作為你——我很高興再次在高水平上開始這個活動，然後謝恩可以隨意添加一些色彩。我認為，正如您所知，HER2-high 經典的 HER2-high 空間比 HER2-low 空間更具活力和發展性。因此，護理標準仍然是雷莫蘆單抗紫杉醇，ORR 和 ITT 族群約為 28%。有許多例子表明 HER2 標靶療法試圖進入這個領域，無論是 2+ 左右的陰性還是 1+ 的。他們有點碰壁，並沒有真正顯示出臨床益處，有時在試驗中表現低於護理標準或安慰劑。

And so looking at what we think would be a meaningful improvement that is related either to the synergy of the biology being pursued or clearly based on the activity of our drug as evidenced by the biomarker data that we are able to use to assess, for example, 4-1BB engagement through Soluble 4-1BB, we think that the 40% bar is a meaningful improvement over standard of care that would really make this a relevant and exciting drug that merit further investment, either on our own or with partners. So that's how we're looking at it in terms of maybe a paucity of competition, they are compared to other areas.

因此，看看我們認為有意義的改進，它要么與正在追求的生物學協同作用相關，要么明顯基於我們藥物的活性，如我們能夠用來評估的生物標誌物數據所證明的那樣，例如，通過Soluble 4-1BB 進行4-1BB 參與，我們認為40% 的標準是對護理標準的有意義的改進，這將真正使其成為一種相關且令人興奮的藥物，值得我們自己或與合作夥伴進一步投資。這就是我們與其他領域相比可能缺乏競爭的角度來看待它的。

But back to fundamentals, 4-1BB is a biology that really drives durability and metabolic fitness of immune cells. And this is the only 4-1BB engager in the space, HER2 high or HER2 low. And so that's also coloring our overall perspective of how we're thinking about this position in both arms. So and then Shane, again, feel free to add any depth around HER2 low in particular that's what Jon was asking about.

但回到根本上，4-1BB 是一種真正推動免疫細胞的耐久性和代謝適應性的生物學。這是該領域唯一的 4-1BB 接合器，HER2 高或 HER2 低。因此，這也影響了我們對雙臂這個位置的整體看法。因此，Shane 再次請隨意在 HER2 低點周圍添加任何深度，特別是 Jon 所問的問題。

Yes, certainly. And just to remind Jon and those listening, we have generated some compelling preclinical data showing the benefit of combining tucatinib with Cinrebafusp Alfa in the HER2 low setting. As Steve indicated, the key benchmark for us is that around tax combination, we do believe that if we see 40% on ORR, it is going to be meaningful and will give us a clear path forward.

是的，當然了。為了提醒 Jon 和聽眾，我們產生了一些令人信服的臨床前數據，顯示了在 HER2 低水平下將 tucatinib 與 Cinrebafusp Alfa 聯合使用的益處。正如 Steve 所指出的，我們的關鍵基準是圍繞稅收組合，我們確實相信，如果 ORR 達到 40%，這將是有意義的，並將為我們提供清晰的前進道路。

Our next question is coming 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。

Welcome, Tim. Congrats, Shane. Maybe starting with 060. It sounds like enrollment is kind of still on track despite obviously the most recent Delta surge. But wondering if you could just remind us on the COVID-19 screening protocol in the trial? And maybe how you would handle a patient who did test positive during the trial in the final analysis? And then on 344, can you disclose if you plan to kick off that dose escalation in the U.S. or Europe or maybe somewhere else? And maybe give a sense of where you think you'll be able to start that dose escalation relative to, say, like a label dose level?

歡迎，蒂姆。恭喜，肖恩。也許從 060 開始。儘管最近達美航空明顯激增，但聽起來入學情況仍在正軌上。但想知道您能否提醒我們試驗中的 COVID-19 篩檢方案？也許你會如何處理在最終分析中試驗期間檢測呈陽性的患者？然後在 344 上，您能否透露您是否計劃在美國、歐洲或其他地方開始劑量升級？也許可以讓您了解一下您認為相對於標籤劑量水平而言，您將能夠開始劑量遞增的位置？

Okay. Thanks, Matt. Let's start with 060. I think we can handle that one pretty efficiently, and then we can talk a little bit more about 344. Although as it's a partner project, we're not at liberty to say as much as we otherwise could for, say CINRA. So as far as 060 COVID-related screening goes, we do screen for COVID-19 throughout the study. So it's performed at screening. It's performed at day minus 1 at the end of the trial and a final follow-up visit. And it's also, as indicated during the duration of the study. If there is a positive test before randomization, the patient is excluded from the trial. And if they get a confirmed diagnosis of on study, there -- the study drug is withdrawn, but they will continue to be monitored.

好的。謝謝，馬特。讓我們從 060 開始。我認為我們可以非常有效地處理這個問題，然後我們可以更多地討論 344。雖然因為它是一個合作夥伴項目，但我們不能自由地談論盡可能多的內容，辛拉說。因此，就 060 COVID 相關篩檢而言，我們在整個研究過程中都會篩檢 COVID-19。所以它是在篩選時進行的。它在試驗和最後一次隨訪結束時的負 1 天進行。正如研究期間所顯示的。如果隨機化前檢測結果呈陽性，則患者將被排除在試驗之外。如果他們在研究中得到確診，研究藥物就會被撤回，但他們將繼續受到監測。

As you know, in terms of execution of the trial, yes, it's a relevant question in view of the lockdowns that have persisted, and have been on and again off again and on again in different regions of Australia. But we are reiterating guidance as you noted, which is data next year at the conclusion of the efficacy phase and then an announcement when we pass through the safety gate into the efficacy phase. And I would say, look, AZ are doing a great job of navigating around the pandemic.

如您所知，就審判的執行而言，是的，鑑於澳洲不同地區持續實施的封鎖措施和一次又一次的封鎖措施，這是一個相關的問題。但正如您所指出的，我們重申了指導意見，即明年功效階段結束時的數據，然後當我們通過安全門進入功效階段時發佈公告。我想說，看，亞利桑那州在應對這場流行病方面做得很好。

Australia is one of the geographies we're working in. We're also doing very well in the Ukraine. And as I say, AZ has done a great job managing things from supply chain to patient recruiting amidst the pandemic. So overall, I remain confident that we'll be able to largely hold the guidance for the program and look forward to keeping everyone abreast of the developments.

澳洲是我們工作的地區之一。我們在烏克蘭也做得很好。正如我所說，在大流行期間，AZ 在管理從供應鏈到患者招募的各個方面都做得很好。因此，總的來說，我仍然相信我們將能夠在很大程度上掌握該計劃的指導，並期待讓每個人都了解最新進展。

And as it relates to 344, we've been really working closely with Servier, as you can imagine, on escalation aspects, including where and at what dose and we are -- we've recycled a lot of learnings from 343. As you know, we started 343 in the U.S., and we started at a very low dose. I mean we're thinking about this a little bit differently because now there have been not only multiple 4-1BB bispecifics in the clinic and a broad body of evidence, including 343 CINRA, that localized 4-1BB agonism is, in fact, safe. And we have a number of 4-1BB/PD-L1 bispecifics that have gone before us a bit ahead of us, and that also is helping to color what we think is a safe starting dose. So we are looking at multiple geographies, even though we have the full U.S. rights and Servier has ex U.S. rights, it's very collaborative on a global scale. And we are doing what we think is best for patients, what's safe for patients, but also is honoring the science that was coming out of the trials that we've seen with bispecifics before us.

就 344 而言，我們一直在與施維雅密切合作，正如你可以想像的那樣，在升級方面，包括地點和劑量以及我們的情況——我們從 343 中吸取了很多經驗教訓。要知道，我們在美國開始了343，而且是從非常低的劑量開始的。我的意思是，我們對這個問題的思考有點不同，因為現在臨床上不僅有多種4-1BB 雙特異性藥物，而且有大量證據（包括343 CINRA），表明局部4-1BB 激動實際上是安全的。我們有許多 4-1BB/PD-L1 雙特異性藥物，它們已經領先我們一些，這也有助於確定我們認為的安全起始劑量。因此，我們正在考慮多個地區，儘管我們擁有完整的美國權利，施維雅擁有除美國的權利，但它在全球範圍內的協作非常緊密。我們正在做我們認為對患者最有利、對患者安全的事情，同時也尊重我們之前所看到的雙特異性藥物試驗中得出的科學結論。

So probably won't get into -- I can't get into specifics yet as to where, but we are really, really pleased with the progress we've made and think that we can -- yes, we can start at doses that reflect the maturing of the 4-1BB bispecific field relative to where we were in the general industry when we started 4-1BB/HER2 several years ago. So I hope that's enough color for the call today.

所以可能不會進入 - 我還不能詳細說明在哪裡，但我們對我們所取得的進展非常非常滿意，並認為我們可以 - 是的，我們可以從以下劑量開始相對於幾年前我們開始4-1BB /HER2 時我們在一般產業的情況，反映了4-1BB 雙特異性領域的成熟。所以我希望今天的電話會議就夠了。

Yes. I guess one last one. On 352, a non-4-1BB bispecific, is that -- is something that Servier, whatever kind of maybe the agonism or management what -- how you want to classify it, to find that Servier has exclusive rights or have you guys thought about -- are there other things that you're looking at for proprietary programs that might be in that 352 program?

是的。我猜是最後一張。在352 上，一個非4-1BB 雙特異性，是－是施維雅的東西，無論是哪種可能的競爭或管理－你想如何分類它，發現施維雅擁有專有權，或者你們認為關於——你們是否正在尋找可能包含在該 352 程式中的專有程式的其他內容？

Yes. So with -- so a couple of basic points. So within the alliance of Servier, we have 2 programs, we have 344 and now 352, and 344 is a program we codevelop. We have full U.S. rights. 352 is a program where Servier has global rights. So we will enjoy milestones and royalties. We have not disclosed the specific building blocks other than -- remember, these are immuno-oncology bispecifics, and we said that it's not 4-1BB. The good thing is that the way we've partnered our platform and our building blocks is they are exclusive on the specific target combination. And so while we're working with 4-1BB/HER2 on our own, we're doing 4-1BB/PD-L1 with Servier, we're also doing 4-1BBx and other things with Seagen. So we can do 4-1BB or other immuno-oncology bispecifics with different combinations, pretty freely. And so we were able to leverage learnings from 352 and the biology that is underpinned there with other potential bispecifics going forward. So you shouldn't just be thinking about this as just 4-1BB.

是的。因此，有幾個基本要點。所以在施維雅聯盟內，我們有2個項目，我們有344個，現在有352個，344是我們共同開發的一個項目。我們擁有完整的美國權利。 352是施維雅擁有全球權利的計畫。所以我們將享受里程碑和版稅。我們沒有透露具體的構建模組，除了——記住，這些是免疫腫瘤學雙特異性藥物，我們說過它不是 4-1BB。好的一點是，我們的平台和建置模組的合作方式是它們在特定目標組合上是專有的。因此，當我們自己開發 4-1BB/HER2 時，我們正在與 Servier 合作開發 4-1BB/PD-L1，我們也與 Seagen 合作開發 4-1BBx 和其他產品。因此，我們可以非常自由地使用不同的組合進行 4-1BB 或其他免疫腫瘤學雙特異性藥物。因此，我們能夠利用從 352 中學到的知識以及以 352 為基礎的生物學以及未來其他潛在的雙特異性抗體。所以你不應該僅僅將其視為 4-1BB。

Our next question comes from Roger Saul with Jefferies.

我們的下一個問題來自傑弗里斯的羅傑·索爾。

Great. And 2 -- So one is the -- I appreciate you provide some details around the thinking for the benchmark for 343. Just curious, how would you take into account the durability kind of the impact for that program in terms of the duration of the response and -- stable disease, how would that impact your go-no-go decision? The second one is for 060. So as far as I know, you announced the safety -- passenger safety this year and announced the efficacy next year. So in terms of the safety announcement, what should we expecting there? And for the efficacy next year, how much data should we expect like the patient number and the dose cohorts, et cetera?

偉大的。 2 - 所以其中一個是 - 我感謝您提供一些關於 343 基準測試思路的細節。只是好奇，您會如何考慮該計劃在持續時間方面的持久性影響反應以及疾病穩定，這將如何影響您的“不去」決定？第二個是針對060的。據我所知，你們今年宣布了安全－乘客安全，明年又宣布了有效性。那麼就安全公告而言，我們該期待什麼？對於明年的療效，我們應該預期多少數據，例如患者數量和劑量組等？

Yes. Thanks, Roger. Maybe I'll start with your last question first. On 060, you had asked, what should we expect in terms of an announcement when we move from the safety into the efficacy phase versus the type of data that we would disclose at the end of the trial. I think that was your -- that was the heart of your question. So we won't be disclosing data until we get through the full trial. And so you would expect, I think, an announcement in due course after we pass through the gate and say, "Hey, we're through the safety gate moving into the efficacy phase," which will then be many more patients, more sites, really, truly a global study.

是的。謝謝，羅傑。也許我會先從你的最後一個問題開始。在 060 上，您曾問過，當我們從安全性階段進入功效階段時，我們應該對公告有何期望，以及我們在試驗結束時披露的數據類型。我認為這就是你的問題的核心。因此，在完成完整試驗之前，我們不會透露數據。因此，我認為，在我們通過大門後，您會期望在適當的時候發佈公告，並說：“嘿，我們已經通過安全門，進入功效階段”，然後將有更多的患者、更多的站點，確實是一項全球研究。

And I think as a reminder, what's on ct.gov, is up to 360 patients in the efficacy portion, which is including 3 doses and placebo. So it will be a large study, and we intend our expectation is next year when we disclose data, we will disclose top line data first and that would be used to inform the community on our intentions to go forward in co-development, which would be the period of time that our option would be triggered, and we want to be able to share the data if, in fact, they're positive and we want to co-develop them.

我想提醒一下，ct.gov 上的療效部分有多達 360 名患者，其中包括 3 劑和安慰劑。因此，這將是一項大型研究，我們的期望是明年當我們披露數據時，我們將首先披露頂線數據，這將用於告知社區我們推進共同開發的意圖，這將是我們的選項被觸發的時間段，如果事實上數據是積極的並且我們希望共同開發它們，我們希望能夠共享數據。

I would imagine that the details of the data would come out consistent with our practice and AZ practice at a medical conference, but that's going to be dependent on a number of factors. But the key top line data next year is what we're guiding on sufficient to inform on our co-development opt-in ambitions.

我想數據的細節將與我們的實踐和 AZ 在醫學會議上的實踐一致，但這將取決於許多因素。但明年的關鍵營收數據是我們所指導的，足以為我們選擇加入的共同開發雄心提供資訊。

And then with respect to 343, you were asking beyond ORR, I think, what we're thinking about in terms of durability of response. And I think we haven't broken out specifics because it's a composite of response, at least 50%, for example, in the HER2 high, plus safety plus durability. We're going to be looking at 6-month disease control rate. And I think going back to the fundamentals of 4-1BB, we certainly want to see an improvement, a meaningful improvement upon what we've seen in rainbow and other targeted therapies that maybe have an impressive or a good ORR, but PFS maybe isn't so -- isn't so durable for patients. Again, Shane, I don't know if there's much more color we can or want to share today. I would let you give an opportunity to add any more color on durability, if you want.

然後，關於 343，我想，你問的是 ORR 以外的問題，我們在回應的持久性方面正在考慮什麼。我認為我們還沒有透露具體細節，因為它是反應的綜合體，例如，在 HER2 高水平中，至少 50%，加上安全性和耐用性。我們將關注 6 個月的疾病控制率。我認為回到4-1BB 的基本原理，我們當然希望看到一種改進，一種比我們在Rainbow 和其他標靶治療中看到的有意義的改進，這些療法可能具有令人印象深刻或良好的ORR，但PFS 可能不是事實並非如此——對病人來說不是那麼持久。再次，Shane，我不知道我們今天是否可以或想要分享更多的顏色。如果您願意，我會讓您有機會在耐用性上添加更多顏色。

Thanks, Steve, and thanks, Roger, for the question. Just what I would add is, again, to remind bulk of our mechanism of action here. So as a 4-1BB agonist, we're going to really reinvigorate the immune system. We're going to drive T cell memory response. And what we saw in our Phase I study was that when patients responded to the agents. They stayed on study for a good amount of time given that these are end-stage patients. So we do believe that 4-1BB has the potential to impact your ability. We also have that Soluble 4-1BB biomarker to ensure that we're getting good modulation of the pathway. So as Steve said, we want to look at the totality of the data and also really have a very rigorous approach to analyzing and assessing what we offer versus the emerging standard of care.

謝謝史蒂夫，也謝謝羅傑提出的問題。我要補充的是，再次提醒大家注意我們的行動機制。因此，作為 4-1BB 激動劑，我們將真正重振免疫系統。我們將驅動 T 細胞記憶反應。我們在第一階段研究中看到的是，當患者對藥物產生反應時。考慮到這些患者都是末期患者，他們花了很長時間進行研究。所以我們確實相信 4-1BB 有潛力影響你的能力。我們還有可溶性 4-1BB 生物標記物，以確保我們對該通路進行良好的調節。因此，正如史蒂夫所說，我們想要查看數據的整體性，並且確實有一個非常嚴格的方法來分析和評估我們提供的服務與新興的護理標準。

It appears we have no additional questions at this time. So I will turn the floor back over to Mr. Yoder for any additional closing remarks.

目前看來我們沒有其他問題。因此，我將把發言權交還給約德先生，讓他發表更多的結論。

No, thank you very much. No closing remarks other than to say thanks again for everyone for your attention and for your continued support of the company. I wish everyone a great day.

不，非常感謝。沒有結束語，只是再次感謝大家的關注以及對公司的持續支持。祝大家有美好的一天。

Ladies and gentlemen, this does conclude today's teleconference and webcast. We thank you for your participation, and you may disconnect your lines at this time.

女士們先生們，今天的電話會議和網路廣播到此結束。我們感謝您的參與，此時您可以斷開線路。