Compass Therapeutics Inc. (CMPX) 2025 Q2 法說會逐字稿

Greetings, and welcome to Compass Therapeutics second quarter 2025 Earnings and Business Update Call. (Operator Instructions) As a reminder, this conference is being recorded. It's now my pleasure to introduce Anna Gifford, Chief of Staff. Thank you. You may begin.

各位好，歡迎參加 Compass Therapeutics 2025 年第二季財報及業務更新電話會議。（操作說明）提醒各位，本次會議正在錄音。現在我很榮幸地向大家介紹幕僚長安娜·吉福德。謝謝。你可以開始了。

Good morning, and thank you for joining us. My name is Anna Gifford. I'm Chief of Staff at Compass Therapeutics. With me today is Dr. Thomas Schuetz, CEO and Vice Chair of the Compass Board. Our CFO, Barry Shin, will also join us for a short Q&A following Tom's comments. Earlier this morning, we released our financial results and a business update for the second quarter. The slide presentation accompanying this webcast and a copy of the press release are available on our website. Please note, we'll be making forward-looking statements on today's webcast. These forward-looking statements are described in our press release issued today and the company's SEC filings. With that, I'd like to turn the call over to Thomas Schuetz. Tom?

早安，感謝各位的參與。我的名字是安娜·吉福德。我是 Compass Therapeutics 的營運長。今天陪我一起的是 Compass 董事會執行長兼副主席 Thomas Schuetz 博士。在湯姆發言結束後，我們的財務長巴里·申也將加入我們，進行一個簡短的問答環節。今天早些時候，我們發布了第二季的財務業績和業務更新。本次網路直播的幻燈片簡報和新聞稿副本可在我們的網站上取得。請注意，我們將在今天的網路直播中發表一些前瞻性聲明。這些前瞻性聲明已在我們今天發布的新聞稿和公司提交給美國證券交易委員會的文件中進行了描述。接下來，我想把電話交給湯瑪斯舒茨。湯姆？

Thank you. We are incredibly excited today to be hosting this call with you this morning. As Anna just mentioned, earlier today, we released our quarterly financials for Q2 2025. In addition to the financials, we also provided very important updates for 3 of our development programs. These updates are summarized on the next slide, and I'll then provide additional details for each of these program updates. Most importantly today, for our lead program, tovecimig, the DLL4 VEGF-A bispecific antibody in the ongoing randomized trial in patients with advanced biliary tract cancer, there are currently fewer total deaths in the study than we have projected. While this disclosure is a simple fact, it is very important to say this sentence differently. More patients are alive today than we have projected. I understand clearly that this is an investor call, but it's so important to reflect on what this could mean for the patients enrolled in this study. I'll update the timing of the survival analysis in 1 minute.

謝謝。今天早上能與大家進行這次電話會議，我們感到無比興奮。正如安娜剛才所提到的，我們今天稍早發布了 2025 年第二季的財務報告。除了財務數據外，我們還提供了 3 個發展項目的重要最新進展。這些更新內容總結在下一張投影片中，接下來我將提供每個專案更新的更多細節。今天最重要的是，對於我們的主導項目 tovecimig（一種針對晚期膽道癌患者的 DLL4 VEGF-A 雙特異性抗體），目前正在進行的隨機試驗中，該研究的總死亡人數比我們預期的要少。雖然這只是一個簡單的事實，但換個方式表達這句話非常重要。目前存活的患者人數比我們預期的要多。我清楚地知道這是一次投資者電話會議，但思考這對參與這項研究的患者意味著什麼至關重要。我將在1分鐘後更新生存分析的時間安排。

Next, for CTX-8371, our PD-1/PD-L1 bispecific antibody, very unexpectedly, we have 2 deep partial responses in the early dose escalation cohorts in the ongoing Phase I study. One partial response is in a patient with non-small cell lung cancer and one partial response is in a patient with triple-negative breast cancer. Later this year, we'll be initiating cohort expansions in patients with non-small cell lung cancer and triple-negative breast cancer. I will describe CT scans for each of these 2 patients in a few minutes. We hope to present these data at a scientific conference later this year. We are also disclosing results from preclinical head-to-head studies of CTX-10726, our proprietary PD-1 VEGF bispecific antibody compared to the leading drug candidate in the class ivonescimab. We will be presenting these data at a scientific conference later this year.

接下來，對於我們的 PD-1/PD-L1 雙特異性抗體 CTX-8371，非常出乎意料的是，在正在進行的 I 期研究的早期劑量遞增隊列中，我們獲得了 2 個深度部分緩解。其中一例部分緩解發生在非小細胞肺癌患者身上，另一例則部分緩解發生在三陰性乳癌患者身上。今年晚些時候，我們將啟動非小細胞肺癌和三陰性乳癌患者的隊列擴展研究。我將在接下來的幾分鐘內分別介紹這兩位患者的CT掃描結果。我們希望在今年稍後的科學會議上展示這些數據。我們也將發表我們專有的 PD-1 VEGF 雙特異性抗體 CTX-10726 與該類領先候選藥物 ivonescimab 的臨床前頭對頭研究結果。我們將在今年稍後的科學會議上公佈這些數據。

So let's begin with tovecimig. This slide summarizes the design of the ongoing randomized study in the United States in patients with advanced biliary tract cancer. This study is a 2:1 randomization of tovecimig plus paclitaxel versus paclitaxel alone. The primary endpoint of the study is overall response rate. We announced those results about 4 months ago. The secondary endpoints in this order are PFS/OS and duration of response. We're using, of course, the hierarchical testing methodology to control for alpha statistical spending in the study. The next slide summarizes the current status of the study that we call Companion-002. On the top right, as I mentioned, we achieved the primary endpoint. So the study is positive by definition. We had a 17.1% overall response rate, about tripling what was seen in the control arm with a p-value of 0.031. On the top left box, I'll come back to this point in 1 minute. The trial was fully enrolled in August of 2024, enrolled 168 patients with advanced biliary tract cancer treated in the second-line setting.

那麼，讓我們從 tovecimig 開始。這張投影片總結了美國正在進行的針對晚期膽道癌患者的隨機研究的設計。本研究採用 2:1 的隨機分組，比較托維西米加紫杉醇與單獨使用紫杉醇的療效。研究的主要終點是總體應答率。我們大約在4個月前公佈了這些結果。次要終點依序為 PFS/OS 和緩解持續時間。當然，我們在研究中使用了分層檢定方法來控制 alpha 統計支出。下一張投影片總結了我們稱為 Companion-002 的研究的當前狀態。正如我之前提到的，我們在右上角實現了主要終點。因此，這項研究從定義上來說就是正面的。我們的整體反應率為 17.1%，約為對照組的三倍，p 值為 0.031。關於左上角的方框，我稍後會在 1 分鐘後回到這一點。該試驗於 2024 年 8 月全面完成招募，共招募了 168 名接受二線治療的晚期膽道癌患者。

As of today, we are currently at greater than 17 months median follow-up in the study. So let's talk about the secondary endpoints of progression-free survival and overall survival. It's actually -- it's hard to say this, but the secondary endpoints are triggered by a total number of deaths in the study. So that's how these time-to-event analyses are commonly done. We need 80% OS events to trigger the analysis of progression-free survival and overall survival. And today, we have fewer total deaths in the study than we had originally projected when we projected that we would be presenting analyses of these endpoints in Q4. We made that projection in April of this year. And since that time, the number of deaths in the study has continued to decline. Clearly, the 80% OS event threshold has not been met. So the analyses of PFS and OS are now projected to occur in Q1 of 2026.

截至今日，該研究的中位追蹤時間已超過 17 個月。那我們來談談無惡化存活期和總存活期這兩個次要終點。實際上——雖然很難說出口，但次要終點是由研究中的總死亡人數觸發的。這就是通常進行此類生存時間分析的方法。我們需要 80% 的 OS 事件才能觸發無惡化存活期和總存活期的分析。而今天，該研究中的總死亡人數比我們最初預測的要少，當時我們預計將在第四季度公佈這些終點的分析結果。我們在今年四月做出了這項預測。自那時以來，該研究中的死亡人數持續下降。顯然，80% 的作業系統事件閾值尚未達到。因此，PFS 和 OS 的分析預計將於 2026 年第一季進行。

I think the bottom of this slide is very important. Recall the study that was titled ABC-06. That study was published in 2021 in Lancet Oncology by (inaudible). That was a randomized study of the 3-drug combination FOLFOX, 5-FU, leucovorin and oxaliplatin in patients with biliary tract cancer treated in the second-line setting. So the exact same population that we're treating in Companion-002. If you look at the Kaplan-Meier curves for that study at 18 months, the overall survival was less than 10% in that study with a median overall survival in the FOLFOX arm of 6.2 months. Where we are today, and again, it's important to point out, these are -- this is a pooled survival number.

我認為這張投影片的底部非常重要。回想一下那項名為 ABC-06 的研究。這項研究於2021年發表在《刺胳針腫瘤學》雜誌。（聽不清楚）這是一項針對接受二線治療的膽道癌患者，採用 FOLFOX、5-FU、亞葉酸鈣和奧沙利鉑三種藥物組合進行的隨機研究。所以，這和我們在 Companion-002 中治療的人群完全一樣。如果查看研究 18 個月時的 Kaplan-Meier 曲線，則研究的總存活率低於 10%，FOLFOX 組的中位總存活期為 6.2 個月。就我們目前的情況而言，再次強調，這些是——這是一個匯總的生存數字。

We're greater than 20% overall survival with greater than 17 months median follow-up. And we probably -- although it's hard to predict, of course, we probably will not be at 80% mortality until we have something like greater than 20 months median follow-up. So very interesting data today, obviously, extremely important. And as we mentioned in our press release, obviously, we don't know this, but it appears that tovecimig could be affecting overall survival in this patient population.

整體存活率超過 20%，中位追蹤時間超過 17 個月。當然，這很難預測，但我們可能要等到中位追蹤超過 20 個月後，死亡率才會達到 80%。今天的數據非常有趣，顯然也極為重要。正如我們在新聞稿中提到的，顯然我們並不知道這一點，但托維西米似乎可能會影響該患者群體的整體存活率。

Okay. Let's now move to CTX-8371, our PD-1/PD-L1 bispecific antibody. Just a reminder of the differentiated mechanism of action here. Recall that this drug emerged from a screen using a proprietary technique at Compass in which we can screen bispecific drug candidates for synergy. That screen identified PD-L1 as a synergistic partner for PD-1 blockade. As I've discussed many times before, that was a rather unexpected scientific discovery. And because of that, we spent a long time investigating the mechanism of action. We published all that data, the PubMed ID for that paper is at the bottom of this slide. We have always envisioned 8371 to be on the leading edge of defining next-generation checkpoint inhibition. This mechanism of action on the right-hand side of this slide, with the bispecific being unequivocally a cell engager and quite fascinatingly, the bispecific actually converts PD-1 positive T cells into PD-1 negative T cells by removing PD-1 from the surface of those cells.

好的。現在我們來看看 CTX-8371，我們的 PD-1/PD-L1 雙特異性抗體。再次提醒這裡的作用機轉有所不同。請記住，這種藥物是透過 Compass 公司採用專有技術篩選出來的，該技術可以篩選雙特異性藥物候選物以尋找協同作用。此篩選結果顯示 PD-L1 是 PD-1 阻斷的協同夥伴。正如我之前多次討論過的，那是一項相當出乎意料的科學發現。正因如此，我們花了很長時間研究其作用機制。我們已經發表了所有數據，該論文的 PubMed ID 在本投影片的底部。我們一直設想 8371 將成為定義下一代檢查點抑制技術的前沿。這張投影片右側所示的作用機制，即雙特異性抗體無疑是一種細胞銜接劑，而且非常令人著迷的是，雙特異性抗體實際上透過從這些細胞表面去除 PD-1，將 PD-1 陽性 T 細胞轉化為 PD-1 陰性 T 細胞。

So it is a very differentiated mechanism of action. And again, we believe that this drug could be on the cutting edge of defining next-generation checkpoint inhibition. We're currently running a Phase I study. This study is a standard 3 plus 3 dose escalation study. Importantly, we, of course, as all Phase I studies do, we started with a minimal dose of 0.1 milligrams per kilogram, and we have finished enrolling the first 4 dosing cohorts, 0.1, 0.3, 1 and 3 milligrams per kilogram. We have not seen any dose-limiting toxicities in those 12 patients.

所以它的作用機制非常獨特。我們再次相信，這種藥物可能處於定義下一代檢查點抑制劑的前沿。我們目前正在進行一項 I 期研究。本研究為標準的 3+3 劑量遞增研究。當然，重要的是，我們像所有 I 期研究一樣，從每公斤 0.1 毫克的最小劑量開始，並且我們已經完成了前 4 個劑量組的招募，分別為每公斤 0.1、0.3、1 和 3 毫克。在這 12 名患者中，我們沒有發現任何劑量限制性毒性。

So again, a 3 plus 3 design, 3 patients times 4 dose levels, 12 patients. We're currently enrolling the fifth dose level, which will be the 10-milligram per kilogram dose level. The patient population in this study, importantly, is all post checkpoint inhibitor. So patients with melanoma, non-small cell lung cancer, head and neck cancer, Hodgkin lymphoma and triple-negative breast cancer are being enrolled in this study.

所以，再次採用 3+3 設計，3 名患者乘以 4 個劑量水平，共 12 名患者。我們目前正在招募第五個劑量水平的受試者，該劑量水平為每公斤體重 10 毫克。值得注意的是，本研究中的患者族群均為接受免疫檢查點抑制劑治療後的患者。因此，患有黑色素瘤、非小細胞肺癌、頭頸癌、何杰金氏淋巴瘤和三陰性乳癌的患者正在參與這項研究。

As I mentioned earlier, we now have 2 deep partial responses in the first patients enrolled in this study. And again, I will emphasize to you that the first dosing cohort was really a de minimis dose. These are CT scans on Slide 10 from a patient in the study with non-small cell lung cancer. For reference, these scan images across the top, the patient is lying on their back, dark color is air, so that's the lungs, lighter color is tissue and the bright white color is bone. Inside of the blue circle at baseline, you can see a 45-millimeter metastatic tumor in this patient, which over time, completely disappears. In fact, this patient had 59 millimeters, 5.9 centimeters, more than 2 inches total of metastatic tumor, which actually all disappeared. Really interestingly in this patient, this patient actually had initial pseudo progression at a lymph node, which has been described with checkpoint inhibitors like Keytruda and Opdivo, and it's interesting to speculate on what that might mean.

正如我之前提到的，目前在這項研究中招募的首批患者中，我們已經獲得了 2 例深度部分緩解。我再次強調，第一批給藥組其實劑量非常小。這些是研究中一位患有非小細胞肺癌的患者的 CT 掃描圖（幻燈片 10）。作為參考，這些掃描影像位於頂部，患者仰臥，深色代表空氣，也就是肺部，淺色代表組織，亮白色代表骨骼。在基線時的藍色圓圈內，可以看到該患者體內有一個 45 毫米的轉移性腫瘤，隨著時間的推移，該腫瘤完全消失了。事實上，這位患者最初有 59 毫米、5.9 公分、超過 2 英寸的轉移性腫瘤，但這些腫瘤全部消失了。非常有趣的是，這位患者實際上在淋巴結處出現了最初的假性進展，這種情況在使用 Keytruda 和 Opdivo 等檢查點抑制劑時曾被描述過，這很值得我們去推測其意義。

Subsequently, all of these patients' target lesions disappeared. We also have 2 patients with non-small cell lung cancer among 5 patients treated so far with prolonged stable disease for a clinical benefit rate of approximately 60%. So on the next slide, I'm going to spend a little bit more time on this slide because this slide is incredibly important. So this is a patient with metastatic triple-negative breast cancer who had 3 metastatic target lesions at baseline. I'm showing 2 of these 3 lesions on this slide. The third lesion was a lymph node. Across the top, same thing as the previous slide, patient lying on her back. Black color is air. So inside the blue circle, you can see a metastatic tumor in the lung, which completely disappears by 8 weeks. On the bottom, this is a sagittal view. So this is a reconstruction where you're looking at the patient from the side.

隨後，所有這些患者的標靶病灶都消失了。到目前為止，我們治療的 5 名患者中有 2 名患有非小細胞肺癌，病情長期穩定，臨床效益約為 60%。所以下一張投影片，我會多花點時間講解一下，因為這張投影片非常重要。這是一位患有轉移性三陰性乳癌的患者，基線時有 3 個轉移標靶病灶。這張投影片上展示了這 3 個病灶中的 2 個。第三處病灶是淋巴結。頂部畫面與上一張投影片相同，病人仰臥。黑色代表空氣。所以在藍色圓圈內，你可以看到肺部的轉移性腫瘤，它在 8 週內完全消失了。底部是矢狀面視圖。這是從側面觀察患者的重建影像。

Inside the blue circle on the bottom left is a metastasis to the pericardium, the lining of the heart. That metastasis is 52 millimeters in size, 5.2 centimeters, more than 2 inches. Both of these tumors completely disappeared. The other target lesion went from 15 millimeters to 7 millimeters. So the total tumor decline in this patient from 87 millimeters to 7 millimeters is greater than a 90% reduction in this patient treated in the fourth-line setting who had previously received pembrolizumab. This patient is 1 out of 3 patients treated in the study with triple-negative breast cancer. So moving to CTX-10726, our proprietary PD-1 VEGF bispecific antibody. So this is a drug candidate that we worked on internally at Compass for about 18 months. We nominated it as a development candidate earlier this year. We have disclosed previously that we have more potent PD-1 blockade in vitro than has been reported for other drugs in the class.

左下角藍色圓圈內的是轉移到心包膜（心臟內膜）的轉移病灶。轉移灶大小為 52 毫米，5.2 厘米，超過 2 英寸。這兩個腫瘤都完全消失了。另一個標靶病灶從 15 毫米縮小到 7 毫米。因此，該患者的腫瘤總體積從 87 毫米減少到 7 毫米，比先前接受過帕博利珠單抗治療的四線患者的腫瘤體積減少 90% 還要大。該患者是研究中接受治療的 3 名三陰性乳癌患者之一。接下來是 CTX-10726，我們專有的 PD-1 VEGF 雙特異性抗體。這是我們在 Compass 內部研發了約 18 個月的候選藥物。今年早些時候，我們提名它作為開發候選項目。我們先前已經披露，我們的藥物在體外對 PD-1 的阻斷作用比同類其他藥物的報告更強。

Over the past 6 months or so, since we disclosed this as a development candidate, we've locked down our CMC process, I think one of the things that we have not talked much about at Compass is we've developed a fair amount of proprietary know-how around bispecific manufacturing and our manufacturing process has commercial level yields for this drug already before we're in Phase I. We're on track to file our IND in the US in Q4 of this year. Today, we're announcing some really interesting preclinical head-to-head comparisons of CTX-10726 with ivonescimab. These next 3 slides are, of course, complicated preclinical experiments, and I'm going to go through these in some detail. In this study, we're using a transgenic mouse model that expresses PD-1 and PD-L1 as human. So the extracellular domains of PD-1 and PD-L1 are knocked in as human, so you can directly test human targeted checkpoint inhibitors in this experiment.

自從我們在過去六個月左右的時間裡公開了該候選藥物的研發進展以來，我們已經完善了CMC製程。我認為我們在Compass公司內部很少提及的一點是，我們已經在雙特異性抗體的生產方面積累了相當多的專有技術，而且在進入I期臨床試驗之前，我們的生產過程已經能夠達到該藥物的商業化產量。我們正按計畫於今年第四季在美國提交IND申請。今天，我們將公佈一些非常有趣的 CTX-10726 與 ivonescimab 的臨床前頭對頭比較研究。接下來的 3 張投影片當然是一些複雜的臨床前實驗，我將詳細解說這些實驗。在本研究中，我們使用了一種基因轉殖小鼠模型，該模型表達與人類相同的 PD-1 和 PD-L1。因此，PD-1 和 PD-L1 的胞外結構域被敲入人源基因，所以你可以在這個實驗中直接測試針對人類的檢查點抑制劑。

Importantly, though, there's no human VEGF in this experiment. I'll come back to that point in a minute. Here, we're directly comparing the PD-1 blocking arms of 10726 with ivonescimab. And you can see that in terms of tumor control in this mouse model in a head-to-head study, 10726 is superior to ivonescimab. For those of you who are looking at these graphs very carefully, you can see that the control and ivonescimab arms end at week 28 because those animals had to be sacrificed due to uncontrolled tumor growth. On the next slide, in the same model, we compare 10726 directly with pembrolizumab. So again, this experiment is simply testing the PD-1 blocking arm of 10726 and comparing that head-to-head with pembrolizumab and 10726 is equivalent to pembrolizumab in this study. The next slide is a little bit more complicated experiment. So this is a xenograft experiment in which a human tumor, a non-small cell lung cancer model called HCC822 is injected into mice. That tumor secretes human VEGF-A.

但要注意的是，本實驗中並沒有使用人類 VEGF。我稍後會再談到這一點。在這裡，我們將 10726 的 PD-1 阻斷劑組與 ivonescimab 進行直接比較。在該小鼠模型的頭對頭研究中，可以看到，就腫瘤控製而言，10726 優於 ivonescimab。仔細觀察這些圖表的人可以看到，對照組和 ivonescimab 組的實驗在第 28 週結束，因為這些動物因腫瘤生長失控而被處死。在下一張投影片中，在同一模型中，我們將 10726 與 pembrolizumab 直接進行比較。所以，這項實驗只是測試了 10726 的 PD-1 阻斷劑，並將其與帕博利珠單抗進行頭對頭比較，在本研究中，10726 與帕博利珠單抗是等效的。下一張投影片展示的是一個稍微複雜一點的實驗。這是一項異種移植實驗，將一種名為 HCC822 的非小細胞肺癌模型的人類腫瘤注射到小鼠體內。此腫瘤分泌人類血管內皮生長因子A (VEGF-A)。

So this experiment tests both PD-1 blockade and VEGF-A targeting. These experiments, of course, are done in immunocompromised mice. So a human immune system is added back to the mice. PBMC is peripheral blood mononuclear cell. So on the bottom left, you can see the control in black. Bevacizumab and ivonescimab are about the same in this experiment and the best drug in this head-to-head experiment is CTX-10726. As I mentioned earlier, we will be presenting these data at a scientific meeting later this year and filing our IND, which is on track for Q4. So on my last slide, we have some updated milestones here. And I think over the next 6 quarters, we have an incredibly rich milestone list here.

因此，該實驗同時測試了 PD-1 阻斷和 VEGF-A 標靶治療。當然，這些實驗都是在免疫功能低下的小鼠身上進行的。於是，人們將人類的免疫系統重新移植到老鼠體內。PBMC是周邊血單核細胞。所以在左下角，你可以看到黑色的控制。在本實驗中，貝伐珠單抗和伊沃西單抗的效果大致相同，而本頭對頭實驗中最好的藥物是 CTX-10726。正如我之前提到的，我們將在今年稍後的科學會議上展示這些數據，並提交我們的IND申請，預計將在第四季完成。在最後一張投影片上，我們有一些更新後的里程碑。我認為在接下來的六個季度裡，我們將迎來一系列意義非凡的里程碑事件。

So let's start with tovecimig. In Q1 of the coming year, we'll read out our important progression-free survival and overall survival from our randomized study. I would imagine that, that readout would be followed by a very robust interaction with the FDA, which would put us into a position to potentially file a license application in the middle of 2026. Of course, we have Fast Track status, Fast Track designation. So I would anticipate that we would get a priority review. We will be initiating our planned basket study for tovecimig following that analysis in patients with DLL4 positive tumors, including potentially gastric cancer, ovarian cancer, hepatocellular cancer, et cetera. Still working on that design, but that study should be ready to go in the coming months. For CTX-471, we're planning to initiate our NCAM positive Basket study later this year. That biomarker was discovered in the Phase I study of CTX-471, and we presented scientific data for that drug twice last year.

那麼，讓我們從 tovecimig 開始。明年第一季度，我們將公佈隨機研究中重要的無惡化存活期和總存活期數據。我想，在那之後，我們將與 FDA 進行非常積極的互動，這將使我們有可能在 2026 年年中提交許可證申請。當然，我們有快速通道資格，快速通道稱號。因此，我預計我們會獲得優先審查。在對 DLL4 陽性腫瘤患者（包括潛在的胃癌、卵巢癌、肝細胞癌等）進行分析後，我們將啟動計劃中的 tovecimig 籃子研究。設計方案仍在完善中，但這項研究應該會在未來幾個月內準備就緒。對於 CTX-471，我們計劃在今年稍後啟動 NCAM 陽性籃子研究。該生物標記是在 CTX-471 的 I 期研究中發現的，我們去年兩次公佈了該藥物的科學數據。

And then finally, for 8371, very important update on that program today. Next step is initiating the cohort expansions in patients with non-small cell lung cancer and triple-negative breast cancer. Those cohort expansions will begin later this year with clinical data from that -- those cohort expansions next year. Hopefully, presenting the dose escalation data at a scientific meeting later this year. Finally, for 10726, the preclinical update that we've provided today, we're going to present that data at a scientific conference later this year, IND filing in Q4, which should put us in a position to read out clinical data next year. And lastly, we also, as part of our disclosure today, we ended Q2 with $101 million in cash, which is cash runway here at Compass into 2027, executing on all these programs and delivering the milestones that you see here. So with that, thank you again for joining the call today. I'm happy to take questions.

最後，關於 8371 號程序，今天有一個非常重要的更新。下一步是啟動非小細胞肺癌和三陰性乳癌患者的隊列擴展研究。這些隊列擴展將於今年稍後開始，臨床數據將於明年公佈。希望今年稍晚能在科學會議上公佈劑量遞增數據。最後，對於我們今天提供的 10726 號藥物的臨床前更新，我們將在今年稍後的科學會議上公佈該數據，並在第四季度提交 IND 申請，這將使我們有機會在明年公佈臨床數據。最後，作為我們今天披露的一部分，我們在第二季末擁有 1.01 億美元的現金，這足以支撐 Compass 營運到 2027 年，執行所有這些項目並實現您在這裡看到的里程碑。那麼，再次感謝各位今天參加電話會議。我樂意回答問題。

(Operator Instructions)

（操作說明）

Andrew Berens with Leerink Partners.

安德魯貝倫斯 (Andrew Berens) 與 Leerink Partners 合作。

Two questions from me. You're allowing crossover on the PAC arm to tovecimig. So is there any chance that the decreased you're seeing reflects performance of [tovecimig] in -- from the drug crossover? Can you give us any idea how many patients are crossing over on (inaudible) from the control arm? And then you mentioned interacting with the FDA. Any comments on potential breakthrough designation? And then I have one on the DLL4 biomarker testing after that.

我有兩個問題。你允許 PAC 臂交叉到 tovecimig。那麼，你看到的下降是否有可能反映了[托維西米]在藥物交叉試驗中的表現？您能否告知我們有多少患者從對照組轉入（聽不清楚）治療組？然後您提到了與美國食品藥物管理局（FDA）的溝通。對於潛在的突破性療法認定，您有什麼看法？然後，我之後還要進行一次 DLL4 生物標記檢測。

Okay. Two important questions. Thanks, Andrew. So on your first question, I just went back to the study schema. So yes, we allow progression -- I mean, we allow crossover in the control arm following centrally confirmed progression. I'm going to answer your second question next. Ballpark, about half the patients crossed over in the control arm. So the statistical methodology that we're using, it's called the rank-preserving structural failure time, was the same methodology used in the IDH1 inhibitor analysis in biliary tract cancer. That statistical analysis adjusts the overall survival analysis for crossover. That is the defined primary method of analysis of the overall survival endpoint.

好的。兩個重要問題。謝謝你，安德魯。關於你的第一個問題，我剛剛回顧了研究計畫。所以，是的，我們允許病情進展——我的意思是，我們允許在中心確認病情進展後，對照組進行交叉治療。接下來我將回答你的第二個問題。據估計，對照組中約有一半的患者轉入了實驗組。因此，我們使用的統計方法稱為維持秩的結構失效時間，與膽道癌中 IDH1 抑制劑分析所採用的方法相同。此統計分析對交叉試驗的總體存活分析進行了調整。這是對總體存活終點進行分析的既定主要方法。

In terms of the general first question, I think potentially, the answer to your question is yes, that potentially even in patients treated in the third-line setting, tovecimig could be extending overall survival, and wouldn't that be fantastic, because if you look at the presentation of the Clarity data, the rank-preserving structural failure time, that analysis was a little bit better than the intent-to-treat analysis, which indicates that the drug was active even after crossover.

就第一個總體問題而言，我認為你的問題的答案可能是肯定的，即使在三線治療的患者中，托維西米也可能延長總生存期，這豈不是很棒嗎？因為如果你看 Clarity 數據的呈現方式，排名保持結構性失效時間分析的結果比意向治療分析略好，這表明即使在交叉治療後，該藥物仍然有效。

Now in our presentation of the overall response data, and that data are currently in our corporate deck on our website, the rate of progressive disease at week 8 was substantially different in the control arm than in the combination arm, 42.1% progression at week 8 versus 16.2% progression. So it doesn't seem like paclitaxel alone is particularly effective. So happy to take your additional question, Andrew.

現在，在我們對整體反應數據的展示中（該數據目前已發佈在我們網站的公司簡報中），第 8 週時，對照組的疾病進展率與聯合治療組有很大不同，第 8 週時分別為 42.1% 和 16.2%。所以看來單獨使用紫杉醇似乎效果不特別好。很高興回答你的其他問題，安德魯。

Yes. And then just on BTD, any thoughts about doing that? Or would it not be -- if you're waiting for the OS analysis, would there not be any real benefit to applying for that at this point?

是的。那麼，關於BTD，大家有什麼想法嗎？或者說，如果你正在等待作業系統分析結果，那麼此時申請該分析難道沒有任何實際好處嗎？

Probably. Yes. No, I think we'll -- that's sort of a work in progress, but it's obviously something we would -- obviously, we're thinking very, very seriously about.

大概。是的。不，我認為我們會——這還在進行中，但顯然這是我們——顯然，我們正在非常非常認真地考慮的事情。

Okay. And then just wondering, the DLL4 biomarker testing, how has that changed from that which was employed in some of the Korean trials?

好的。另外，我想問一下，DLL4 生物標記檢測與韓國一些試驗中使用的檢測方法相比，有哪些變化？

It's the same. We tech transferred that analysis into the US, and we're using -- we used that and we're continuing to use that in the evaluation of biopsy specimens from some of the studies that we've done.

是一樣的。我們將該分析技術轉移到了美國，我們正在使用——我們已經使用過它，我們正在繼續使用它來評估我們所做的一些研究中的活檢標本。

Okay.

好的。

Thank you.

謝謝。

Thanks.

謝謝。

Maury Raycroft with Jefferies

莫里·雷克羅夫特與傑弗里斯

This is [Amin] on for Maury. A couple of questions from us. You mentioned the PFS OS analysis happening in 1Q '26. Can you clarify whether enough events might come in during Q4 to allow for analysis in early Q1? Or are you expecting that 80% of event threshold to actually be reached in Q1 itself? And I have a follow-up.

這是阿明為莫里主持的節目。我們有幾個問題。您提到 PFS OS 分析將在 2026 年第一季進行。您能否說明一下，第四季是否會有足夠多的事件發生，以便在第一季初進行分析？或者您預計第一季就能達到 80% 的事件門檻？我還有一個後續問題。

Sure. Thanks for the question. That's a very hard question. What we had originally projected is that we would have 80% -- we would hit the 80% event threshold by the end of Q3. What we know today is that's not going to happen. So beyond that, it's almost impossible to project accurately. And what we have simply said is we believe that the analysis will read out in Q1.

當然。謝謝你的提問。這是一個很難的問題。我們最初的預測是，我們將達到 80%——到第三季末，我們將達到 80% 的事件閾值。我們現在知道，這種情況不會發生。因此，除此之外，幾乎不可能進行精確預測。我們只是簡單地表示，我們相信分析結果將在第一季公佈。

All right. Sounds good. And when it comes to the readout, should we be thinking about a full data set release? Or will some of the data be held back for medical meeting presentation?

好的。聽起來不錯。至於資料公佈方面，我們是否應該考慮發布完整的資料集？或者部分數據是否會保留下來，用於在醫學會議上進行展示？

Yes. I think we're planning to present a priority data set at that time, which would be PFS, OS, demographic data and top line safety data with the rest of the data to be presented at a medical meeting.

是的。我認為我們計劃屆時公佈一組優先數據，其中包括 PFS、OS、人口統計數據和主要安全性數據，其餘數據將在醫學會議上公佈。

Okay, very helpful.

好的，很有幫助。

Michael Schmidt with Guggenheim

邁克爾·施密特與古根漢

Thanks for taking my questions. I had just a logistical question. So if the Companion-002 study, in fact, succeeds on PFS and OS, I guess what else needs to be done to support a possible BLA submission around CMC, for example, how far along are you with some of the other sections that are required for BLA submission? And then I had a separate question on 8371.

謝謝您回答我的問題。我只是想問一個後勤方面的問題。所以，如果 Companion-002 研究確實在 PFS 和 OS 方面取得了成功，那麼為了支持可能的 CMC 方面的 BLA 申請，還需要做些什麼呢？例如，BLA 申請所需的其他一些部分進展如何？然後我還有一個關於 8371 的問題。

Okay. Thanks, Michael. Yes, great question. Our so-called PPQ batches; process, performance, qualification, the batches that are required for a BLA submission are all underway. So our CMC process should be very much locked down. So that should not be limiting.

好的。謝謝你，麥可。是的，問得好。我們所謂的 PPQ 批次（工藝、性能、資格）以及 BLA 申請所需的批次都在進行中。因此，我們的CMC流程應該嚴格把控。所以這不應該成為限制因素。

Okay. Great. And then yes, on 8371, interesting new data here today. Yes, could you just provide some additional commentary on the dose level where these responses were seen? And yes, have you seen any other patients with tumor size reduction? Or in fact, I think you mentioned two other patients with lung cancer with stable disease. Did you see tumor shrinkage in those as well?

好的。偉大的。是的，關於 8371，今天這裡有一些有趣的新數據。是的，您能否就觀察到這些反應的劑量水平提供一些補充說明？是的，您還看過其他腫瘤體積縮小的患者嗎？或者事實上，我想您還提到了另外兩名病情穩定的肺癌患者。你也觀察到這些病例的腫瘤縮小了嗎？

So a couple of questions there. The non-small cell lung cancer response was at the 0.3 milligram per kilogram dose level and the triple-negative breast cancer response was at the 3.0 milligram per kilogram dose level. We're not releasing any other clinical data at this time. Again, hoping to present all of that data at a scientific meeting later this year, including the patients from the 10 mg per kg cohort.

所以這裡有幾個問題。非小細胞肺癌的療效在每公斤0.3毫克劑量水準下達到，三陰性乳癌的療效在每公斤3.0毫克劑量水準下達到。我們目前不會公佈任何其他臨床數據。再次希望在今年稍後的科學會議上展示所有這些數據，包括每公斤體重 10 毫克劑量組的患者數據。

Okay. Anything else you can share on the treatment history of the two case studies? Obviously, they did have a PD-1 inhibitor before, but anything else you could share there?

好的。關於這兩個病例的治療史，您還有其他資訊可以分享嗎？顯然，他們之前確實有一種PD-1抑制劑，但您還能分享其他資訊嗎？

Yes. Most of these patients, sort of a typical Phase I population, many lines of therapy. This patient with triple-negative breast cancer had three lines of therapy in the metastatic setting, including previously some neoadjuvant and adjuvant therapy. So typical Phase I population, heavily pretreated, all the patients in the study having received prior therapy with a checkpoint inhibitor.

是的。這些患者大多屬於典型的 I 期臨床試驗族群，接受過多種治療方案。這位患有三陰性乳癌的患者在轉移性疾病治療中接受了三線治療，包括之前的一些新輔助和輔助治療。因此，典型的 I 期臨床試驗族群，接受過大量預處理，研究中的所有患者都曾接受過免疫檢查點抑制劑治療。

Great. Thank you.

偉大的。謝謝。

Biren Amin with Piper Sandler

比倫·阿明與派珀·桑德勒

Hey, yeah, hi guys. Thanks for taking my questions. Maybe just to start on tovecimig. Your projections for the OS analysis and time lines for Q1, is that based on the current event rate that you're seeing? You mentioned that the event rate had slowed since your projection earlier this year? Or is the projection based on a lower event rate from what one would anticipate? I guess I'm trying to assess confidence on the Q1 analysis.

嘿，是的，大家好。謝謝您回答我的問題。或許可以先從 tovecimig 開始。您對第一季作業系統分析和時間表的預測，是基於您目前觀察到的事件發生率嗎？您提到過，自今年稍早您做出預測以來，事件發生率已放緩？或者，該預測是基於低於預期事件發生率的情況？我想評估的是對第一季分析的信心。

Yes. Great question. So I think the short answer to your question, Biren, is yes. Our projection is based on the current mortality rate that we're seeing. And I think over the last approximately four or five months, we've clearly seen a decrease. So we're basing the Q1 projection on the current rate.

是的。問得好。所以，比倫，我認為你問題的簡短答案是肯定的。我們的預測是基於我們目前看到的死亡率。而且我認為在過去的四、五個月裡，我們已經明顯看到了下降的趨勢。因此，我們是根據目前的成長率來預測第一季的業績。

Got it. Okay. And then as far as the Phase I IST, any update on that in terms of when we can expect first data from the quadruplet combination?

知道了。好的。那麼關於第一階段IST，關於四聯體試驗的首批數據，有什麼最新進展嗎？

No, I don't have an update on that study at this time. That study is enrolling patients at MD Anderson, but I don't have an update today.

不，目前我還沒有關於那項研究的最新進展。這項研究正在MD安德森癌症中心招募患者，但我今天沒有最新消息。

Okay. And then I do have several questions on 8371. Congrats on the data in the dose escalation cohort. So I just wanted to maybe ask for the non-small cell lung cancer patient, the patient had 0 centimeters of tumor. why is that patient not considered a complete response?

好的。然後，關於 8371，我還有幾個問題。恭喜你們在劑量遞增隊列中獲得的數據。所以我想問一下，對於那位非小細胞肺癌患者，他的腫瘤直徑為0厘米，為什麼不能算完全緩解呢？

Yes. That is a great question. And actually, that question applies to the triple-negative breast cancer patient as well because -- so with this patient, this patient had some non-target lesions that did not qualify the patient as a CR. For the triple-negative breast cancer patient, the target lesion 3 is actually a lymph node and a lymph node less than 10 millimeters in the short access, and this is 7 by RECIST 1.1 is not pathological. So this patient's target lesion response was actually read as a CR. This patient also had nontarget lesions that did not disappear. So because of that, this patient is a RECIST PR.

是的。這是一個很好的問題。實際上，這個問題也適用於三陰性乳癌患者，因為——對於這位患者來說，她有一些非目標病灶，這不符合完全緩解的標準。對於三陰性乳癌患者，目標病灶 3 實際上是一個淋巴結，且在短程通路中小於 10 毫米，根據 RECIST 1.1 標準，這屬於非病理性病變。因此，該患者的標靶病灶反應實際上被判定為完全緩解。該患者還存在未消失的非目標病變。因此，該患者被評為 RECIST PR。

Got it. And then maybe just a few more on 8371. You mentioned that the triple-negative patient had prior pembro. What about the non-small cell lung cancer patient? Did they have prior PD-1? And what was the therapy? And then I guess -- and then also, can you talk about what their PD-L1 status was when they received 8371?

知道了。然後可能還會再加幾個在 8371 上。您提到這位三陰性患者之前患有帕博利珠單抗。那麼，非小細胞肺癌患者的情況又是如何呢？他們之前有過PD-1感染嗎？治療方法是什麼？然後我想——另外，您能否談談他們在獲得 8371 時 PD-L1 狀態如何？

What a great question. So the answer to that question is, I don't know. We did not read biopsy patients before the Phase I study. I do know that the non-small cell lung cancer patient at their diagnosis, so take that for what it's worth, had a very low PD-L1 expression. But we did not re-biopsy patients for the Phase I study.

真是個好問題。所以這個問題的答案是，我不知道。在 I 期研究之前，我們沒有對活檢患者進行研究。我知道，這位非小細胞肺癌患者在確診時，PD-L1 表現量非常低，僅供參考。但我們並未對 I 期研究中的患者進行再次活檢。

Stephen Willey with Stifel

Stephen Willey 與 Stifel

This is (inaudible) on for Steve. Congrats on the progress. I just have two

這是（聽不清楚）給史蒂夫的。恭喜你取得進展。我只有兩個

questions, one on tovecimig, one on CTX-10726. Just starting with the tovecimig, Tom, like I know that you will present patient demographics later when both PFS and OS analysis are ready. But like the fact that you haven't accrued like enough -- like any death events, how confident are you that these patients are actually reflective of like historical clinical trials and just like a real-world data. So that's the first question. And second question on the CTX-10726. By the way, very nice, impressive preclinical data in terms of tumor shrinkage. What can you -- what can you say about the safety data? And are you guys planning to present any preclinical data like prior to or soon after IND submission?

問題，一個關於 tovecimig，一個關於 CTX-10726。Tom，我們先從托維西米格開始，我知道你會在 PFS 和 OS 分析完成後再公佈患者的人口統計資料。但是，就像你還沒有累積足夠的數據一樣——例如任何死亡事件，你有多大把握這些患者能夠真正反映歷史臨床試驗和真實世界的數據？這是第一個問題。關於 CTX-10726 的第二個問題。順便說一句，腫瘤縮小的臨床前數據非常出色，令人印象深刻。關於安全數據，您有什麼看法？你們是否計劃在提交IND申請之前或之後不久公佈任何臨床前數據？

Thank you.

謝謝。

Thanks, Complex first question about demographics in this study. I'll simply say it's hard to know without the final data set and cross-trial comparisons to demographics. It's -- I think I probably can't really answer that. I think I'll simply say that the randomization in this study was stratified by three important prognostic variables, performance status, 0 versus 1. Metastatic disease outside the liver, yes or no. The vast majority of these patients had metastatic disease outside the liver, something like 80%.

謝謝，這是本研究中關於人口統計學的第一個複雜問題。我只能說，如果沒有最終數據集和跨試驗的人口統計數據比較，很難知道結果。這個問題——我想我可能無法回答。我只想說，這項研究中的隨機化是按三個重要的預後變數進行分層的，分別是體能狀態、0 分與 1 分。是否存在肝外轉移性疾病？是/否。這些患者中絕大多數（約 80%）患有肝外轉移性疾病。

And it was finally, it was stratified by anatomic subtype, intrahepatic cholangiocarcinoma or other. So because the randomization is stratified, I think the demographics in the two treatment arms will be very well balanced. So I think that's very important. Yes, thanks for your comment on 10726. Yes, we will be presenting scientific data for 10726 at a scientific conference later this year.

最後，它按解剖亞型進行分層，分為肝內膽管癌或其他類型。由於隨機分組是分層的，我認為兩個治療組的人口統計數據將非常平衡。所以我認為這非常重要。是的，謝謝你對10726的評論。是的，我們將在今年稍後的科學會議上公佈 10726 的科學數據。

Aydin Huseynov with Ladenburg Thalmann.

艾丁·侯賽諾夫與拉登堡·塔爾曼。

Hi, good morning. Congrats on the progress this quarter. A couple of questions from us. So first, on tovecimig, the question is about the duration of response in the tovecimig arm of the trial. Could you provide any comments on the duration of response? And are these patients who initially responded still on the trial?

您好，早安。恭喜本季取得的進展。我們有幾個問題。首先，關於托維西米格，問題是試驗中托維西米格組的療效持續時間。您能否就回覆時長提供一些意見？這些最初有反應的患者是否仍在參與試驗？

Thanks, Aydin. So I went back to the study schema here. So we don't have any analysis of duration of response at this time because in the statistical methodology, the first two secondary endpoints to be analyzed are PFS and then OS. So duration will be the last secondary endpoint analyzed. So I don't have any information on that. I don't -- most of the patients are in survival follow-up. I don't have a number today on how many patients are still on the study. I'm sorry about that Aydin.

謝謝你，艾丁。所以我回到了這裡的研究方案。因此，目前我們還沒有對反應持續時間進行任何分析，因為在統計方法中，首先要分析的兩個次要終點是 PFS，然後是 OS。因此，持續時間將是最後分析的次要終點。所以我對此一無所知。我不這麼認為——大多數患者都在進行生存追蹤。我今天還沒有關於還有多少患者仍在參與這項研究的具體數字。艾丁，我很抱歉。

Okay. That, that's.

好的。就是這樣。

Okay.

好的。

Okay. That's okay. Another question is on VEGF PD-1 bispecific. So I'm just trying to understand how the future is going to look like for this asset. So in the future, how do you see the regulatory path for your VEGF PD-1? And is it going to be as a single-arm path or like a head-to-head to pembro or nivo, just curious about the -- your thoughts on this.

好的。沒關係。另一個問題是關於 VEGF PD-1 雙特異性抗體。所以我想了解這項資產的未來發展前景如何。那麼，您認為未來 VEGF PD-1 的監管路徑會是怎麼樣的呢？它會以單臂路線的形式出現，還是會像與彭博或尼沃那樣正面交鋒？我只是好奇——你對此有何看法。

Sure. I think great question, obviously. So I think the way we've been thinking about this is I think the regulatory path depends on very thoughtful indication selection. And where our thinking is with this drug is where we want to explore indications where both VEGF targeting and PD-1 targeting as monotherapies have been demonstrated to be effective.

當然。我覺得這當然是個好問題。所以我認為我們一直以來思考這個問題的方式是，監管路徑取決於經過深思熟慮的適應症選擇。我們對這種藥物的設想是，我們希望探索在 VEGF 標靶和 PD-1 標靶作為單一療法均已證明有效的適應症。

So what are some of those? So renal cell, nivolumab and VEGF kinase inhibitors, gastric cancer where the VEGF receptor blocking antibody, (inaudible) is approved as well as PD-1 targeted agents. Obviously, hepatocellular cancer, where bevacizumab and atezolizumab are frontline standard of care and maybe something like endometrial cancer, where VEGF kinase inhibitors have also been shown to be effective.

那麼，這些具體有哪些呢？因此，腎細胞癌、納武利尤單抗和 VEGF 激酶抑制劑、胃癌（其中 VEGF 受體阻斷抗體，（聽不清楚）以及 PD-1 標靶藥物均已獲批准。顯然，在肝細胞癌中，貝伐珠單抗和阿特珠單抗是一線標準療法；子宮內膜癌等疾病中，VEGF 激酶抑制劑也已被證明有效。

And I think for some of these indications, say, the post-PD-1 VEGF patient with renal cell cancer, I think those could be single-arm pathways to approval. I think the non-small cell lung cancer indication is going to be, obviously, as you know, incredibly competitive, and we would probably not go there first.

我認為對於某些適應症，例如 PD-1 VEGF 治療後的腎細胞癌患者，我認為這些適應症可以透過單臂途徑獲得批准。我認為非小細胞肺癌這一適應症領域，顯然競爭會非常激烈，正如你所知，我們可能不會先涉足這一領域。

Very helpful.

很有幫助。

Robert Driscoll with Wedbush Securities.

韋德布希證券公司的羅伯特·德里斯科爾。

Thanks. Good morning, Tom. Maybe just a follow-up on Biren's question. For the 8371 expansion cohorts, do you expect to select patients based on PD-L1 expression at this stage?

謝謝。早上好，湯姆。或許可以作為對比倫問題的後續。對於 8371 個擴展隊列，您是否計劃在這個階段根據 PD-L1 表達來選擇患者？

So we don't. We expect to leave the selection criteria the same as for the dose escalation portion of the study.

所以我們不這樣做。我們預期選擇標準將與研究中劑量遞增部分的選擇標準保持一致。

Okay. And then anything you can say with regards to immune-related adverse events here kind of acknowledging that we're still in dose escalation.

好的。然後，關於免疫相關不良事件，你可以說的任何話都承認我們仍在劑量遞增階段。

Sure. Yes. It's interesting. We believe that the way this drug might work, although we have some data to support this preclinically. Ultimately, we're going to need a lot more data to support what I'm about to say. So just that caution. We believe that this drug could be anchored in the tumor microenvironment by PD-L1, where it can provide very high concentration PD-1 blockade in the tumor microenvironment. So I'll simply say that in the first 4 dosing cohorts, we've not seen any dose-limiting toxicities. And look, as a next-generation checkpoint inhibitor, there's no reason to believe that the safety profile might not be better.

當然。是的。很有意思。我們認為這種藥物可能的作用機制是這樣的，儘管我們有一些臨床前數據支持這一點。最終，我們需要更多的數據來佐證我接下來要說的觀點。所以，提醒一下就好。我們認為這種藥物可以透過 PD-L1 錨定在腫瘤微環境中，從而在腫瘤微環境中提供非常高濃度的 PD-1 阻斷。因此，我簡單地說，在前 4 個給藥組中，我們沒有看到任何劑量限制性毒性。而且，作為新一代的檢查點抑制劑，沒有理由相信它的安全性不會更好。

Got it. I'm looking forward to the update here. Thanks, Tom.

知道了。我期待這裡的更新。謝謝你，湯姆。

Thanks, Robert.

謝謝你，羅伯特。

Sean McCutcheon with Raymond James

肖恩麥卡琴與雷蒙德詹姆斯

Hey guys, thanks for the question. Just a couple for me. How are you thinking about the necessary magnitude of benefit over paclitaxel on PFS given that paclitaxel not a commonly used chemo in second-line biliary tract cancer. And what gives you confidence that you've cleared the PFS bar for clinical adoption over FOLFOX? And then separately, could you give some context on kind of how you're thinking around OS and how FDA may be approaching OS and what you need to see as a trend on an ITT basis versus a [process adjusted] basis?

大家好，謝謝你們的提問。就我一個人用。您認為在二線膽道癌化療中，紫杉醇並非常用的化療藥物，那麼在無惡化存活期（PFS）方面，與紫杉醇相比，所需的獲益幅度是多少？是什麼讓您確信您已經通過了 PFS 測試，可以取代 FOLFOX 方案進行臨床應用？另外，您能否單獨談談您是如何看待 OS 的，以及 FDA 可能會如何看待 OS，以及您需要從 ITT 角度和 [流程調整] 角度觀察哪些趨勢？

Thanks, Sean. So for the first question, I have sort of a two-part answer perhaps. So the first part, I'll simply summarize what the statistical power calculations are for the PFS analysis. So the PFS analysis is 80% powered for a hazard ratio of approximately 0.6. So a hazard ratio of 0.6 or lower would, I think, obviously be spectacular. I take your point about paclitaxel, and I think our overall response rate data where we had 42.1% radiographic progression in the paclitaxel arm at week 8 suggests that the median PFS in the paclitaxel arm is going to be in the 2 to 2.5-month range, about the same as has been seen with FOLFOX, for example, in the FOLFOX versus FOLFIRI randomized trial.

謝謝你，肖恩。對於第一個問題，我的回答或許可以分成兩個部分。所以第一部分，我將簡單地總結 PFS 分析的統計功效計算方法。因此，PFS 分析在風險比約為 0.6 時具有 80% 的統計功效。所以，我認為，風險比為 0.6 或更低顯然是非常棒的。我明白你關於紫杉醇的觀點，我認為我們的總體緩解率數據顯示，紫杉醇組在第 8 週的放射學進展率為 42.1%，這表明紫杉醇組的中位 PFS 將在 2 到 2.5 個月的範圍內，與 FOLFOX 相比，例如在 FOLFOX 與 FOLFIRI 的隨機試驗中觀察到相同的隨機試驗。

We recently completed some market research that was done by sort of a very well-known leading market research firm. And I think we were very pleasantly surprised at the KOL feedback on PFS from that market research, which frankly suggests that a hazard ratio of 0.6 would be off the charts. So KOLs would be happier just given what they know about FOLFOX with even less benefit. But a hazard ratio of 0.6 would be incredible. The second question, I don't have any information on your second question, never got any specific feedback from FDA about the difference between the ITT analysis and the RPSFT analysis of overall survival.

我們最近完成了一項市場調查，這項研究是由一家非常知名的領先市場調查公司進行的。我覺得我們對市場調查中 KOL 對 PFS 的回饋感到非常驚喜，坦白說，這表明風險比為 0.6 將會非常驚人。因此，KOL們即使獲得的收益較少，也會因為了解FOLFOX而感到更滿意。但0.6的風險比將是難以置信的。關於第二個問題，我沒有相關信息，也從未從 FDA 那裡得到任何關於 ITT 分析和 RPSFT 分析在總生存期方面差異的具體反饋。

Understood, thanks.

明白了，謝謝。

(Operator Instructions)

（操作說明）

Joe Pantginis with H.C. Wainwright.

喬·潘特吉尼斯與H.C.溫賴特。

So first, on tovecimig, first, a logistical question. Can you just remind us the level of meetings that you've already had with the FDA and what is planned and what role the potential for accelerated approval based on response rates have had in those discussions, number 1.

首先，關於 tovecimig，首先是一個後勤問題。第一，您能否提醒我們一下，您已經與 FDA 進行了哪些級別的會議，有哪些計劃，以及基於反應率的加速批准的可能性在這些討論中發揮了什麼作用？

And then number two, obviously, there's a lot of talk here about the control arm. There's a lot of variables that are in this study. You've obviously talked about -- it doesn't seem like paclitaxel in the control arm is contributing to anything with regard to the data you're seeing. So with that, I'm going to ask about what are your thoughts on the perceived risk of any better-than-expected impact from the control arm, specifically from the fact that, obviously, these patients are receiving excellent clinical care. I mean it sounds like a rhetorical question, but I just wanted to get your views on the perceived risk

其次，很顯然，這裡有很多關於控制臂的討論。這項研究涉及很多變數。顯然你已經談到了——就你看到的數據而言，對照組的紫杉醇似乎沒有任何作用。因此，我想問您對對照組可能出現的超出預期效果的風險有何看法，特別是考慮到這些患者顯然正在接受優秀的臨床護理。我的意思是，這聽起來像個反問句，但我只是想了解你對這種風險的看法。

Yes, sure. Thanks, Joe. Maybe I'll take the second one first. So again, in terms of the control arm, again, I'm going to go back to the rate of progressive disease in the control arm at week 8, 42.1% radiographic progression at week 8. So we already have substantial progressive disease at week 8. And PFS, of course, is defined in the standard way, either radiographic progression or death.

當然可以。謝謝你，喬。也許我會先選第二個。所以，再說一下對照組的情況，我再次回到第 8 週對照組的疾病進展率，第 8 週的放射學進展率為 42.1%。所以到了第 8 週，我們已經出現了明顯的病情進展。當然，PFS 的定義是標準的，即放射學進展或死亡。

We, of course, have not done any analysis of PFS in the study because we're trying to be very rigorous statistically. But just based on the rate of progression at week 8, it doesn't seem like we're seeing something outlandish in the control arm. In terms of a formal interaction with the FDA, we had a formal interaction with the FDA regarding the design of this study. So that was, of course, some time ago. So we would plan to have a much more robust and formal interaction with the FDA after we get the PFS and OS readouts from the study in the first half of '26.

當然，我們沒有對研究中的 PFS 進行任何分析，因為我們力求在統計上做到非常嚴謹。但僅從第 8 週的進展速度來看，對照組似乎並沒有出現任何異常情況。在與 FDA 的正式互動方面，我們與 FDA 就本研究的設計進行了正式互動。當然，那已經是好幾年前的事了。因此，我們計劃在 2026 年上半年獲得該研究的 PFS 和 OS 數據後，與 FDA 進行更強大和正式的互動。

I appreciate that. And then just quickly on 8371, can you take any broad strokes right now about the design and/or numbers expected within the dose expansion cohorts for the 2 indications stated?

我很感激。那麼，關於 8371，您現在能否大致介紹一下針對上述兩種適應症的劑量擴展隊列的設計和/或預期人數？

Sure. Yes. So what we are currently planning in patients with triple-negative breast cancer, non-small cell lung cancer, a randomized study to two doses, a small randomized study, something like 50 patients ballpark in order to start to explore a couple of doses, have not picked the doses yet because we want to get all the data from the 10 mg per kg dose level. We should have most of that data by the end of this quarter, which would put us in a position to initiate those cohort expansions in Q4.

當然。是的。因此，我們目前計劃對三陰性乳癌、非小細胞肺癌患者進行一項隨機研究，比較兩種劑量，這是一項小型隨機研究，大約有 50 名患者，以便開始探索幾種劑量，但我們還沒有確定劑量，因為我們希望獲得 10 毫克/公斤劑量水平的所有數據。到本季末，我們應該能夠獲得大部分數據，這將使我們能夠在第四季度啟動這些隊列擴展計劃。

There are no further questions at this time. I would like to turn the floor back over to Tom for closing remarks.

目前沒有其他問題了。我想把發言權交還給湯姆，讓他做總結發言。

Great. Thank you so much. And I'm just going to go to the last slide here again. Thank everyone for joining today and just highlight what the next 12 to 18 months could look like for us, readout from our randomized trial in patients with biliary tract cancer, followed by a robust interaction with FDA and then potentially a license application, which would obviously be incredibly exciting.

偉大的。太感謝了。我再回到上一張投影片。感謝大家今天到場，我們想重點介紹一下未來 12 到 18 個月我們的計劃：我們將公佈膽道癌患者隨機試驗的結果，隨後與 FDA 進行深入溝通，並有可能提交上市許可申請，​​這顯然會令人非常興奮。

A couple more clinical trials with tovecimig and 471. And I think really exciting today our cohort expansion for 8371. And as I mentioned earlier, we have always positioned 8371 to be on the cutting edge of defining next-generation checkpoint inhibition and the data that we've reported today really puts us on track to achieving that goal.

托維西米格和471還有幾項臨床試驗。今天，我們8371屆學員的擴招真的令人興奮。正如我之前提到的，我們一直將 8371 定位為定義下一代檢查點抑制的最前沿技術，而我們今天公佈的數據確實使我們朝著實現這一目標邁進了一步。

And then lastly, our PD-1 VEGF-A bispecific antibody 10726. We have preclinical differentiation from ivonescimab, really looking forward to getting that drug into patients in 2026 and reporting Phase I clinical data. Thanks again, everybody. Happy to follow up with any questions that any of you folks might have.

最後，是我們的 PD-1 VEGF-A 雙特異性抗體 10726。我們已在臨床前研究方面與 ivonescimab 進行了區分，非常期待在 2026 年將該藥物應用於患者，並公佈 I 期臨床數據。再次感謝大家。我很樂意解答各位可能提出的任何問題。

Thank you. This will conclude today's conference. You may disconnect your lines at this time and thank you for your participation.

謝謝。今天的會議到此結束。您可以暫時斷開線路，感謝您的參與。