Arcus Biosciences Inc (RCUS) 2024 Q3 法說會逐字稿

Good afternoon. Thank you for attending today's Arcus Biosciences third-quarter 2024 earnings call. My name is Tamiya and I will be your moderator for today's call. (Operator instructions)

午安.感謝您參加今天的 Arcus Biosciences 2024 年第三季財報電話會議。我的名字是 Tamiya，我將擔任今天電話會議的主持人。（操作員指令）

I would now like to pass the conference over to your host, Pia Eaves, Vice President of Investor Relations. You may proceed.

現在，我想將會議交給主持人、投資者關係副總裁 Pia Eaves。您可以繼續。

Hello everyone, and thank you for joining us on today's conference call to discuss Arcus's third quarter 2024 financial results and pipeline updates, including our upcoming presentation of ARC-10 data at SITC.

大家好，感謝您參加今天的電話會議，討論 Arcus 2024 年第三季的財務業績和管道更新，包括我們即將在 SITC 展示的 ARC-10 數據。

I'd like to remind you that on this call, management will make forward-looking statements, including statements about our cash runway and our expected clinical development milestones and timelines. All statements other than historical facts reflect the current beliefs and expectations of management, and involve risks and uncertainties that may cause our actual results to differ from those expressed. Those risks and uncertainties are described in our most recent quarterly report on Form 10-Q that has been filed by the with the SEC.

我想提醒您，在這次電話會議上，管理層將做出前瞻性陳述，包括有關我們的現金流量以及我們預期的臨床開發里程碑和時間表的陳述。除歷史事實之外的所有陳述均反映管理層當前的信念和期望，並涉及可能導致我們的實際結果與所表達的結果不同的風險和不確定性。這些風險和不確定性在我們向美國證券交易委員會提交的最新 10-Q 表季度報告中有所描述。

Today you'll hear from our CEO, Terry Rosen; CMO, Dimitry Nuyten; COO, Jennifer Jarrett; and CFO, Bob Goeltz. We'll also be joined by our President, Juan Jaen for questions after prepared remarks.

今天您將聽到我們的執行長 Terry Rosen 的演講；首席行銷官，Dimitry Nuyten；營運長，Jennifer Jarrett；和財務長 Bob Goeltz。我們的總裁胡安·哈恩 (Juan Jaen) 也將在準備好的演講後與我們一起回答問題。

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

說完這些，我會把電話轉給特里。

Thank you very much, Pia, and thank you all for joining us today. As we are heading into 2025, our highest priority is to launch our late stage development program for HIF-2 alpha inhibitor casdatifan. As you know, just two weeks ago, we presented initial data from our ARC-20 study evaluating cas in late line, clear-cell RCC in an oral plenary session at the ENA meeting.

非常感謝，Pia，也感謝大家今天加入我們。隨著我們即將進入 2025 年，我們的首要任務是啟動 HIF-2 阿爾法抑制劑 casdatifan 的後期開發計劃。如您所知，就在兩週前，我們在 ENA 會議的口頭全體會議上介紹了 ARC-20 研究的初步數據，該研究評估了晚期透明細胞 RCC 中的 cas。

These data clearly validates our conviction that cas will be a best-in-class HIF-2 alpha inhibitor, demonstrating improvement in every key efficacy measure that we analyze versus belzutifan. As you know, belzutifan is the only HIF-2 alpha inhibitor on the market today.

這些數據清楚地證實了我們的信念，即 cas 將成為一流的 HIF-2 阿爾法抑制劑，與 belzutifan 相比，我們分析的每個關鍵功效指標都有所改善。眾所周知，貝祖替凡是目前市面上唯一的 HIF-2 阿爾法抑制劑。

So let's go to slide 5, and I'll recap the highlights from our dataset. First off, the rate of primary progression in the 100 milligram daily expansion cohort was only 19% and was similarly low in the 50 milligram daily expansion cohort. In fact, the rate of primary progression for the combined 60 patients in the 50 milligram and 100 milligram expansion cohorts was approximately half of what was observed in LITESPARK-005.

那麼讓我們轉到第 5 張投影片，我將回顧我們資料集中的亮點。首先，每日 100 毫克擴展組的原發性進展率僅為 19%，而每日 50 毫克擴展組的原發性進展率也同樣較低。事實上，50 毫克和 100 毫克擴展組中 60 名患者的原發性進展率約為 LITESPARK-005 中觀察到的一半。

Keep in mind that the primary progression rate and disease control rate, DCR are the only data points that are fully mature and will not change. So this is really a huge difference for the molecule.

請記住，原發性進展率和疾病控制率、DCR 是唯一完全成熟且不會改變的數據點。這對於分子來說確實是一個巨大的差異。

Second, we reported a 34% ORR and 25% confirmed ORR for the 100 milligram cohort with two out of three unconfirmed responses pending confirmation and also multiple stable disease patients still on therapy. As of the data cutoff, every responder across both cohorts remained on treatment with the exception of that one patient whose response did not confirm.

其次，我們報告稱，100 毫克組的 ORR 為 34%，確認的 ORR 為 25%，三分之二的未確認反應有待確認，還有多名病情穩定的患者仍在接受治療。截至數據截止時，除一名未確認反應的患者外，兩個群組中所有有反應的患者均仍在接受治療。

The belzutifan data actually provide good precedent for the kinetics of response with HIF-2 alpha inhibition. So this is important. Approximately 60% of responses occurred within six months of treatment and an additional 20% occurred in each of the ensuing six month periods.

貝祖替凡數據實際上為 HIF-2 阿爾法抑制的反應動力學提供了良好的先例。所以這很重要。約 60% 的反應發生在治療後六個月內，另外 20% 的反應發生在隨後的每個六個月內。

So that goes out to 18 months. These data illustrate why our ORR could, and in reality more likely should further improve across both cohorts. Keep in mind, those follow-up times are 8 months and 11 months respectively for 50 and 100 milligrams.

所以總共要 18 個月。這些數據說明了為什麼我們的 ORR 能夠、並且實際上更有可能在兩個群體中進一步改善。請記住，50 毫克和 100 毫克的追蹤時間分別為 8 個月和 11 個月。

The ARC-20 data also demonstrated that the activity of cas is extremely durable. As of the data cutoff, a median PFS had not been reached even with that 11 months median follow-up. Recall that belzutifan was approved based upon its PFS of 5.6 months. And our median PFS, which we expect to report in early 2025, should easily exceed that benchmark.

ARC-20 數據也顯示 cas 的活動極為持久。截至數據截止，即使經過 11 個月的中位數隨訪，仍未達到中位 PFS。回想一下，貝祖替凡是根據其 5.6 個月的 PFS 而獲得批准的。我們預計將在 2025 年初報告的中位 PFS 應該會輕鬆超過該基準。

Given that PFS is the registration endpoint, this will be another important source of differentiation. Our spider plot show multiple patients either past or approaching the 52 week duration of treatment, and you also see deepening of responses with time. I want to emphasize that these data were generated in a heavily pretreated patient population relative to that of LITESPARK-005.

鑑於 PFS 是註冊終點，這將是另一個重要的區分來源。我們的蜘蛛圖顯示，多名患者的治療時間已過或接近 52 週，您還會看到隨著時間的推移，反應不斷加深。我想強調的是，這些數據是在相對於 LITESPARK-005 而言接受過大量治療的患者群體中產生的。

Specifically, approximately 25% of the patients enrolled in ARC-20 wouldn't be ineligible for LITESPARK-005. For the 50 milligram cohort, despite only eight months median follow-up at the data cutoff, we reported a 14% primary progression rate, a 25% ORR and just over 21% confirmed ORR with the one unconfirmed responder pending confirmation, and a very impressive almost remarkable DCR of 86%.

具體來說，大約 25% 的 ARC-20 患者不符合 LITESPARK-005 的資格。對於 50 毫克組，儘管在數據截止時僅進行了 8 個月的中位隨訪，但我們報告了 14% 的原發性進展率、25% 的 ORR 和略高於 21% 的已確認 ORR（有一例未經確認的應答者有待確認），以及非常令人印象深刻的幾乎驚人的 86% 的 DCR。

One of the confirmed responders was a complete response. Beyond the responders, and again, another important point, nearly 40% of patients still continued on therapy with stable disease, including a few whom are extremely close already to the 30% response threshold, and you can see that in the spider plots.

其中一位確認的應答者是完全應答者。除了有反應的患者之外，另一個重點是，近 40％ 的患者在病情穩定後仍繼續接受治療，其中一些患者的病情已經非常接近 30％ 的反應閾值，您可以在蜘蛛圖中看到這一點。

While this data set is still evolving and will continue to improve, we now have two different cohorts that are demonstrating clear efficacy differentiation relative to that of belzutifan and there's a lot more data to come.

雖然這個數據集仍在發展並將繼續改進，但我們現在有兩個不同的群體，與貝祖替芬相比，它們顯示出明顯的療效差異，而且還會有更多數據。

On slide 6, we show the data that we expect to share from ARC-20 throughout 2025. We plan to present additional data from the 100 milligram and 50 milligram cohorts of ARC-20, including more mature ORR and median PFS that will be early next year. Later in the year, we plan to present initial data from the 150 milligram and the 100 milligram once daily tablet expansion cohorts. So that's another 60 patients worth of data.

在第 6 張投影片上，我們展示了預計在 2025 年期間從 ARC-20 分享的數據。我們計劃在明年年初提供 ARC-20 100 毫克和 50 毫克隊列的更多數據，包括更成熟的 ORR 和中位 PFS。今年晚些時候，我們計劃展示每日一次 150 毫克和 100 毫克藥片擴展組的初步數據。這又有 60 名患者的數據。

We also plan to present initial safety data from our cas plus cabo expansion cohort. To date, the safety data from this cohort, which we already shared with the FDA as part of our pre-Phase 3 meeting are consistent with the profiles of the individual drugs and the dose intensity of 100 milligrams of cas and 60 milligrams of cabo has been maintained.

我們還計劃提供來自 cas plus cabo 擴展隊列的初步安全數據。到目前為止，我們已在第 3 階段前會議上與 FDA 分享的該隊列的安全性數據與各個藥物的特性一致，並且保持了 100 毫克 cas 和 60 毫克 cabo 的劑量強度。

Given the importance of the ARC-20 data, and that's important to us, it's important to you, it's important to investigators. The ongoing evolution of the data set and the multiple cohorts that we've enrolled, we're considering additional opportunities to provide updates from this study in the more near term. We remain full steam ahead towards the initiation of our first Phase 3 study, PEAK-1. The investigator enthusiasm for the study is incredibly high, which we believe will support rapid enrollment.

鑑於 ARC-20 數據的重要性，這對我們、對您、對調查人員都很重要。隨著數據集和我們招募的多個隊列的不斷發展，我們正在考慮在近期提供更多機會來提供這項研究的更新資訊。我們全力以赴啟動第一階段 3 期研究 PEAK-1。研究人員對這項研究的熱情非常高，我們相信這將支持快速招募。

Now let me switch gears to domvanalimab, our Fc-silent anti-TIGIT antibody. Just yesterday, the SITC abstract was released with data from Part 1 of our ARC-10 study, which evaluated dom plus zimberelimab, that's our anti-PD-1 antibody, versus zim versus chemotherapy in first-line PD-L1 high non-small cell lung cancer.

現在讓我轉到 domvanalimab，我們的 Fc 沉默抗 TIGIT 抗體。就在昨天，SITC 摘要發布了，其中包含我們 ARC-10 研究第 1 部分的數據，該研究評估了 dom 加 zimberelimab（即我們的抗 PD-1 抗體）與 zim 以及化療在一線 PD-L1 高非小細胞肺癌中的療效。

As a reminder, we terminated the study for strategic reasons to focus on STAR-121, our chemo combination stud. But the early termination gave us both an opportunity to generate and now present a data set from a study that was conducted under Phase 3 conditions.

提醒一下，我們出於策略性原因終止了這項研究，轉而專注於 STAR-121（我們的化療組合研究）。但提前終止給了我們一個機會來產生並展示在第 3 階段條件下進行的研究的資料集。

On slide 27, we summarize the abstract. We show that dom plus zim exceeded zim monotherapy on ORR, PFS and OS. For both PFS and OS, we achieved a hazard ratio below 0.65, which is far better than the threshold considered clinically meaningful in this setting. With median PFS of 11.5 months and median OS not reached for dom zim, these results are meaningfully above contemporary benchmark studies for anti-PD-1 monotherapy.

在第 27 張投影片上，我們總結了摘要。我們表明，dom 加 zim 在 ORR、PFS 和 OS 方面優於 zim 單藥療法。對於 PFS 和 OS，我們實現了低於 0.65 的風險比，這遠遠好於在這種情況下被認為具有臨床意義的閾值。對於 dom zim 來說，中位 PFS 為 11.5 個月，中位 OS 未達到，這些結果顯著高於當代抗 PD-1 單藥療法的基準研究。

Dimitry is going to discuss these data in detail, but I want to make two important points. First off, these data reaffirm the growing recognition that Fc-silent anti-TIGIT antibodies have a differentiated safety profile relative to that of Fc-enabled antibodies.

Dimitry 將詳細討論這些數據，但我想強調兩點。首先，這些數據再次證實了人們日益增長的認識，即 Fc 沉默的抗 TIGIT 抗體與 Fc 啟用的抗體相比具有差異化的安全性。

There are only two Fc-silent TIGIT antibodies in late stage clinical development today, Dom and AstraZeneca's anti-PD-1 anti-TIGIT bispecific antibody. In the last few months, AstraZeneca presented two data sets for their antibody in first-line non-small cell lung cancer and first-line gastric cancer. Interestingly, both data sets look very similar to our own, specifically similar efficacy as well as AE rates that are in line with anti-PD-1 therapy alone. That's an important component of the profile.

目前，只有兩種 Fc 沉默的 TIGIT 抗體處於後期臨床開發階段，即 Dom 和阿斯特捷利康的抗 PD-1 抗 TIGIT 雙特異性抗體。在過去的幾個月裡，阿斯特捷利康公佈了其抗體在治療一線非小細胞肺癌和第一線胃癌的兩組數據。有趣的是，這兩組數據看起來與我們自己的非常相似，特別是相似的療效以及與單獨抗 PD-1 療法一致的 AE 率。這是個人資料的重要組成部分。

In contrast, for the Fc-enabled anti-TIGIT antibodies, we continue to see reports of higher rates of immune-related adverse events and treatment related discontinuations. Combining the Fc-enabled antibodies with chemotherapy absolutely seems to exacerbate these issues.

相較之下，對於 Fc 支持的抗 TIGIT 抗體，我們繼續看到有關免疫相關不良事件和治療相關停藥發生率較高的報告。將 Fc 抗體與化療結合似乎絕對會加劇這些問題。

The second point that I want to make is that with this ARC-10 data set, which will be presented in more detail at SITC, the ARC-7 results in PD-L1 high non-small cell lung cancer that we shared last year and the EDGE gastric data that we presented earlier in this year at ASCO, we now have three compelling data sets supporting the potential of dom zim in both lung and gastric cancers.

我想說的第二點是，透過這個 ARC-10 數據集（將在 SITC 上更詳細地介紹）、我們去年分享的 ARC-7 在 PD-L1 高非小細胞肺癌中的結果以及我們今年早些時候在 ASCO 上展示的 EDGE 胃數據，我們現在有三個令人信服的數據集，支持 dom zim 在肺癌和胃癌中的潛力。

For our EDGE gastric study, we showed a median PFS of 13 months for dom zim in first-line gastric cancer, which meaningfully surpassed the PFS of seven to eight months seen in benchmark studies. And in the first half of next year, we expect to present mature overall survival from the study. Meanwhile, we continue to execute on our three Phase 3 trials for dom zim.

對於我們的 EDGE 胃癌研究，我們表明 dom zim 在一線胃癌中的中位 PFS 為 13 個月，這顯著超過了基準研究中七到八個月的 PFS。我們預計在明年上半年展示研究的成熟整體存活率。同時，我們繼續對 dom zim 進行三項 III 期試驗。

In first-line gastric cancer with our STAR-221 study, we have the potential to be first to market with an anti-TIGIT antibody in this setting. With this study fully enrolled, we're actively preparing for readout and potential submission to health authorities. We believe this setting alone is a $3 billion-plus opportunity.

在STAR-221研究的第一線胃癌治療中，我們有可能成為第一個在此領域推出抗TIGIT抗體的產品。隨著這項研究的全面展開，我們正在積極準備宣讀並可能提交給衛生當局。我們相信，光是這一點就意味著超過 30 億美元的商機。

In lung cancer, with our STAR-121 and PACIFIC-8 studies, the latter in partnership with AstraZeneca, we have a potentially differentiated anti-TIGIT combination in the two settings we're pursuing. First-line and Stage 3 non-small cell lung cancer. We continue to evaluate our statistical analysis plans for all our dom zim studies to ensure that they're optimized for probability of success, but also while addressing the largest number of patients.

在肺癌領域，透過我們的 STAR-121 和 PACIFIC-8 研究（後者與阿斯特捷利康合作），我們在所追求的兩種環境中獲得了潛在差異化的抗 TIGIT 組合。一線和第三期非小細胞肺癌。我們將繼續評估所有 dom zim 研究的統計分析計劃，以確保它們能夠優化成功機率，同時也能解決最多數量的患者的問題。

We also continue to advance the other programs in our pipeline. We've initiated PRISM-1, our Phase 3 study evaluating quemli plus chemo. That's quemli is our CD73 inhibitor in first-line metastatic pancreatic cancer. And with Taiho's opt-in to this program, they're executing the study in Japan. We believe this could be a transformative first-line therapy in a disease to where with dismal outcomes for patients.

我們還在繼續推動正在籌備的其他項目。我們已經啟動了 PRISM-1，這是我們的第三階段研究，用於評估 quemli 聯合化療。這就是 quemli，這是我們用於一線轉移性胰臟癌的 CD73 抑制劑。由於 Taiho 選擇加入該計劃，他們正在日本進行這項研究。我們相信這可能成為一種變革性的第一線治療方法，用於治療那些對患者預後不佳的疾病。

Early next year, we expect to advance AB801, a highly selective AXL inhibitor into expansion cohorts in non-small cell lung cancer. Our relationships with Gilead, AstraZeneca and Taiho are strong, and they've enabled us to aggressively advance all of our programs in a highly resource efficient manner. With $1.1 billion in cash and investments and runway into mid-2027, we're comfortably funded for multiple clinical readouts.

明年初，我們預計將高選擇性 AXL 抑制劑 AB801 推進到非小細胞肺癌的擴展隊列中。我們與吉利德、阿斯特捷利康和太和公司的關係非常牢固，這使我們能夠以高度資源高效的方式積極推進所有專案。我們擁有 11 億美元現金和投資，並且能夠持續到 2027 年中期，我們有足夠的資金進行多項臨床讀數。

Before we go to the ARC-10 results, I'd like to turn it over to Jen to discuss our development plans and the market opportunity for cas.

在我們了解 ARC-10 結果之前，我想先與 Jen 討論我們的開發計劃和 cas 的市場機會。

Thanks, Terry. Starting with PEAK-1, our first Phase 3 trial for cas in clear cell RCC, we expect to begin this study in the first half of next year. The design is shown on slide 23 of our deck. The study will enroll approximately 700 patients and will compare cas plus cabozantinib to cabo monotherapy in IO experienced clear cell RCC.

謝謝，特里。從 PEAK-1 開始，這是我們針對透明細胞 RCC 中的 cas 進行的首個 3 期試驗，我們預計將於明年上半年開始這項研究。該設計展示在我們簡報的第 23 張投影片上。研究將招募約 700 名患者，並將比較 cas 合併卡博替尼與 cabo 單藥治療在 IO 經歷的透明細胞 RCC 的療效。

Cabo is the standard of care in this setting, so clinicians are extremely comfortable administering cabo and adjusting its dosing to optimize both cabo's efficacy and safety. We believe that the vast majority of the second line patient population, approximately 80% will be eligible for PEAK-1, given this study only includes patients who received prior treatment with cabo in the first line setting.

Cabo 是這種情況下的標準治療方法，因此臨床醫生可以非常放心地使用 Cabo 並調整其劑量，以優化 Cabo 的療效和安全性。我們相信，鑑於這項研究僅包括在第一線接受過 cabo 治療的患者，絕大多數二線患者（約 80％）將有資格接受 PEAK-1 治療。

You can see on slide 24 that this study targets an approximately 11,000 patient population in the US. Assuming a treatment time in excess of 15 months, this is a $2 billion-plus market opportunity in the G7 countries alone.

您可以在第 24 張投影片上看到，這項研究針對的是美國約 11,000 名患者。假設治療時間超過 15 個月，那麼僅在 G7 國家，這便是超過 20 億美元的市場機會。

We are also excited to move into the IO-naive setting with our collaboration with AstraZeneca to combine cas with their anti-PD-1 CTLA-4 bispecific volrustomig. The anti-CTLA-4 PD-1 combination ipi-nivo currently has about one-third market share in the first-line setting, and that share is growing, given the preferable safety and tolerability profile of IO based regimens relative to those of TKIs.

我們也很高興透過與阿斯特捷利康的合作進入 IO 初治環境，將 cas 與他們的抗 PD-1 CTLA-4 雙特異性 volrustomig 結合。抗 CTLA-4 PD-1 組合藥物 ipi-nivo 目前在一線治療中佔有約三分之一的市場份額，而且由於 IO 方案相對於 TKI 方案具有更好的安全性和耐受性，因此該份額還在增長。

By combining cas with volru, we have the potential to develop a first and best-in-class TKI sparing regimen. This represents a patient population of approximately 12,000 in the US alone. And assuming a potential median treatment duration of 20 months, the total addressable market would exceed $3 billion across the G7 countries.

透過將 cas 與 volru 結合，我們有可能開發出首個也是一流的 TKI 節約方案。這意味著僅在美國就有大約 12,000 名患者。假設潛在的中位治療時間為 20 個月，那麼 G7 國家的總目標市場規模將超過 30 億美元。

Additionally, we are working to further expand the development program of cas into other RCC subpopulations, and you'll see us add additional cohorts to ARC-20 in the coming months. We remain confident in cas's ability to play a very meaningful role in the RCC market.

此外，我們正在努力將 cas 的開發計劃進一步擴展到其他 RCC 亞群，您將看到我們在未來幾個月內向 ARC-20 添加更多隊列。我們仍然相信 cas 有能力在 RCC 市場中發揮非常重要的作用。

Today, patients cycle through different treatment options for years, receiving multiple different TKIs with seven different TKIs on the market. But today, in the HIF-2 alpha field, it is just cas and belzutifan.

如今，患者多年來不斷嘗試不同的治療方案，接受多種不同的 TKI 治療，而市面上有七種不同的 TKI。但如今，在HIF-2 alpha領域，只有cas和belzutifan。

I'd now like to turn the call over to Dimitri to discuss our newly released data for dom zim in lung cancer.

現在我想將電話轉給 Dimitri，討論我們最新發布的關於肺癌 dom zim 的數據。

Thanks, Jen. Our abstract for ARC-10 was released yesterday morning and data will be presented in a late-breaker poster session this Friday at SITC. ARC-10 was originally a global Phase 3 study evaluating dom and zim versus zim versus chemotherapy in patients with PD-L1 high non-small cell lung cancer. This is important since the trial conduct with the same rigor as would be expected from a registrational Phase 3.

謝謝， Jen。我們對 ARC-10 的摘要已於昨天上午發布，數據將於本週五在 SITC 的最新海報會議上展示。ARC-10最初是一項全球性3期研究，評估dom和zim與zim與化療對PD-L1高非小細胞肺癌患者的療效。這很重要，因為試驗的進行與註冊階段 3 的預期同樣嚴格。

Though ARC-10 was discontinued for strategic reasons, we continue to follow patients. And now with over two years of median follow-up, we are presenting our first overall survival data for dom and zim in any setting. As you will see, the results are supportive of dom's ability to meaningfully extend survival in patients.

儘管 ARC-10 因戰略原因而停止，但我們仍繼續追蹤患者。現在經過超過兩年的中位隨訪，我們首次展示了 dom 和 zim 在任何環境下的整體生存數據。正如您將看到的，結果證實了 dom 能夠顯著延長患者的生存期。

Starting with the design on slide 30, the trial was randomized 2:2:1. So there were 38 patients in the dom and zim arm, 40 patients in the zim monotherapy arm and 17 patients in the chemotherapy arm. Baseline characteristics were generally well balanced across the arms with some prognostic imbalances favoring the chemotherapy arm. The data cutoff for this analysis was May 17, 2024, and the median follow-up was 24.5 months.

從投影片 30 上的設計開始，試驗以 2:2:1 的比例隨機進行。因此，dom 和 zim 組有 38 名患者，zim 單藥治療組有 40 名患者，化療組有 17 名患者。各組的基線特徵大致上是均衡的，但有些預後不平衡有利於化療組。本次分析的資料截止日期為 2024 年 5 月 17 日，中位追蹤時間為 24.5 個月。

On slide 31, we show the Kaplan Meier curve for overall survival. These results are quite impressive. In fact, even with two years of median follow-up, a median OS has not been reached for dom and zim. The hazard ratio for overall survival was 0.64, a result that is very clinically meaningful.

在投影片 31 上，我們展示了整體存活率的 Kaplan Meier 曲線。這些結果令人印象深刻。事實上，即使經過兩年的中位隨訪，dom 和 zim 仍未達到中位 OS。整體存活的風險比為0.64，此結果具有非常大的臨床意義。

Additionally, the zim control arm performed right in line with the benchmark studies of pembrolizumab in this setting with a median overall survival of 24.4 months. When compared to chemotherapy, zim demonstrated a hazard ratio of 0.63 for overall survival. Again, this is right in line with KEYNOTE-042 and other benchmark studies.

此外，zim 對照組的表現與 pembrolizumab 的基準研究結果完全一致，中位總存活期為 24.4 個月。與化療相比，zim 的整體存活風險比為 0.63。再次，這與 KEYNOTE-042 和其他基準研究完全一致。

The poster presentation will also highlight additional data, including progression free survival and overall response rates, which also showed a clear benefit for dom and zim over zim and put zim performance in line with the benchmark studies for pembrolizumab.

海報展示還將重點介紹其他數據，包括無進展生存期和總體反應率，這些數據也顯示了 dom 和 zim 相對於 zim 的明顯優勢，並使 zim 的性能與 pembrolizumab 的基準研究一致。

The safety profile was also consistent with prior observations for dom and zim. Immune mediated adverse events were similar for dom and zim relative to those for zim alone at 23.7% and 20% respectively. These results are substantially different from data reported from studies with the Fc-enabled anti-TIGIT antibodies where immune-mediated adverse events, and treatment interruptions and discontinuations have been meaningfully higher than the anti-PD-1 or PD-L1 alone arm. In fact, it has been cited as the cause of trial failures.

安全性概況也與 dom 和 zim 的先前觀察結果一致。dom 和 zim 的免疫介導不良事件與單獨使用 zim 的免疫介導不良事件相似，分別為 23.7% 和 20%。這些結果與使用 Fc 支持的抗 TIGIT 抗體的研究報告的數據有很大不同，在這些研究中，免疫介導的不良事件以及治療中斷和停止的發生率明顯高於單獨使用抗 PD-1 或​​ PD-L1 的組別。事實上，它被認為是審​​判失敗的原因。

The compelling data from ARC-10, both for efficacy and safety, increases our confidence that combining dom and zim with chemotherapy and STAR-121 will further improve outcome and provide lung cancer patients with the best chance of success in their first-line treatment.

ARC-10 在療效和安全性方面均提供了令人信服的數據，這增強了我們的信心：將 dom 和 zim 與化療和 STAR-121 相結合將進一步改善結果，並為肺癌患者提供一線治療成功的最佳機會。

Now I'd like to turn the call over to Bob to cover our financials.

現在我想將電話轉給鮑伯來討論我們的財務問題。

Thanks, Dimitry. Our cash as of the end of the third quarter was $1.1 billion as compared to $1 billion as of the end of the second quarter. Our cash position was bolstered by a $100 million collaboration continuation payment from Gilead.

謝謝，Dimitry。截至第三季末，我們的現金為 11 億美元，而截至第二季末的現金為 10 億美元。吉利德提供的 1 億美元合作延續付款增強了我們的現金狀況。

Turning to our P&L. We recognized GAAP revenue for the third quarter of $48 million, which compares to $39 million for the second quarter of this year. Our revenue was primarily driven by collaborations with Gilead and Taiho, and in the third quarter included $15 million resulting from the Taiho opt-in for quemli in July. We continue to expect to recognize GAAP revenue of approximately $30 million for the fourth quarter of 2024.

轉向我們的損益表。我們確認第三季的 GAAP 收入為 4,800 萬美元，而今年第二季的 GAAP 收入為 3,900 萬美元。我們的收入主要來自於與 Gilead 和 Taiho 的合作，第三季的收入包括 7 月 Taiho 選擇加入 quemli 所帶來的 1500 萬美元。我們繼續預期 2024 年第四季的 GAAP 收入約為 3,000 萬美元。

Our R&D expenses for the third quarter are stated net of reimbursements from Gilead and were $123 million as compared to $115 million in the second quarter of this year. We continue to expect modest increases in R&D expenses for the fourth quarter of 2024. G&A expenses were $30 million for the third quarter and were flat compared to the second quarter of this year. We expect G&A expenses to remain stable for the fourth quarter.

我們第三季的研發費用扣除吉利德的報銷費用後為 1.23 億美元，今年第二季為 1.15 億美元。我們繼續預計 2024 年第四季的研發費用將小幅增加。第三季的一般及行政開支為 3,000 萬美元，與今年第二季持平。我們預計第四季的一般及行政開支將保持穩定。

Finally, we expect our cash and investments balance at the end of 2024 to be between $950 million and $985 million as compared to our prior guidance of $885 million to $925 million. We expect these resources to fund operations into mid-2027. Our guidance excludes additional potential opt-in payments and milestones from our partners. For more details regarding our financial results, please refer to our earnings press release from earlier today and our 10-Q.

最後，我們預計 2024 年底的現金和投資餘額將在 9.5 億美元至 9.85 億美元之間，而先前預期為 8.85 億美元至 9.25 億美元。我們預計這些資源將為 2027 年中期的營運提供資金。我們的指導不包括來自合作夥伴的額外潛在選擇加入付款和里程碑。有關我們財務業績的更多詳細信息，請參閱我們今天早些時候發布的收益新聞稿和我們的 10-Q。

I'll now turn it back to Terry for concluding remarks

現在我將請特里做最後發言

So thank you all again for joining us this afternoon. As I mentioned earlier on the call, we have a lot coming, and that starts with our SITC presentation for dom zim on Friday, followed by additional presentations from ARC-20 and the initiation of our first Phase 3 study for cas over the coming months. As we head into 2025, we'll be approaching our first Phase 3 data set for STAR-221 in first-line gastric cancer. We appreciate your interest and support of Arcus.

再次感謝大家今天下午加入我們。正如我之前在電話會議上提到的，我們有很多事情要做，首先是周五為 dom zim 進行的 SITC 演示，然後是來自 ARC-20 的額外演示，以及未來幾個月內為 cas 啟動的第一階段 3 期研究。隨著我們進入 2025 年，我們將獲得 STAR-221 在一線胃癌治療中的第一個 3 期數據集。感謝您對 Arcus 的關注與支持。

And I'll now open the call for questions.

現在我開始回答問題。

(Operator Instructions)

（操作員指令）

Yigal Nochomovitz, Citi.

花旗的 Yigal Nochomovitz。

Hi. Terry and team. Thanks for taking the question. I'm getting a lot of interest in cas and people are asking about the potential for Gilead's opt-in. Can you provide any more color there as far as whether they're specified windows? Obviously, you mentioned that you need a qualifying data package.

你好。特里和團隊。感謝您回答這個問題。我對 CAS 很感興趣，人們正在詢問吉利德選擇加入的可能性。您能否提供更多詳細資訊以說明它們是否是指定的視窗？顯然，您提到您需要一個合格的資料包。

Does that mean it could the monotherapy? Or is Gilead interested in seeing some of the combo data with volru or the initial combo data with cas plus cabo coming up soon? That's the first question. Thanks.

這是否意味著它可以作為單一療法？或者吉利德有興趣看到即將發布的 volru 的一些組合數據或 cas plus cabo 的初始組合數據？這是第一個問題。謝謝。

Yes. So we have aligned with Gilead on what data is needed for the qualifying data package. We're very close to meeting that data requirement. So we will be delivering a package to them relatively soon. And as we've been saying, we expect a decision to be made either late this year or early next year.

是的。因此，我們已經與吉利德就合格資料包所需的資料達成了一致。我們已非常接近滿足該數據要求。因此我們將很快向他們發送包裹。正如我們一直所說的，我們預計將在今年年底或明年年初做出決定。

Okay. Thank you. Okay. And then I'm just curious, was there any preclinical work done with volru and cas to sort of just do a quick validation of the combo safety in NHPs or something before going into this collaboration with AZ?

好的。謝謝。好的。然後我很好奇，在與 AZ 合作之前，是否與 volru 和 cas 進行過任何臨床前工作，以快速驗證 NHP 中的組合安全性或其他什麼？

No. There was no preclinical work done. It's very typical sort of situation where you have two molecules, well-defined profiles that simply taking into to do those studies initially in human.

不。沒有進行任何臨床前工作。這是一種非常典型的情況，你有兩個分子，它們具有明確的特徵，最初只是用來在人體上進行研究。

Okay. And then last one is, I'm curious about (inaudible). Obviously, you had the data, I believe, at ASCO for the ARC-9. What are you thinking there in terms of the later development? There is the other cohort, which is the second-line cohort, which is Cohort A. Is that what you're waiting for before you decide with a registrational study, given the obviously very, very strong OS that you saw in the third line?

好的。最後一個問題，我很好奇（聽不清楚）。顯然，我相信您擁有 ASCO 的 ARC-9 資料。對於後續的發展，您有什麼想法嗎？還有另一個隊列，即第二線隊列，即隊列 A。

No. To be honest, it's just a matter of us moving. So we're extremely excited about the data set, and we're just working through with Gilead. You can see, obviously, we're starting a number of later-stage trials, and we still have the full portfolio going. So we're working through what our next steps will be, and we'll share them once they're defined together with Gilead.

不。說實話，這只是我們行動的問題。因此，我們對該數據集感到非常興奮，並且我們正在與 Gilead 合作。您可以看到，顯然我們正在開始一些後期試驗，並且我們仍在進行完整的產品組合。因此，我們正在研究下一步的行動，一旦與吉利德共同確定了行動計劃，我們就會分享。

Okay. Thank you, Terry.

好的。謝謝你，特里。

Thanks, Yigal. I appreciate it.

謝謝，伊加爾。我很感激。

Li Watsek, Cantor Fitzgerald.

李沃特塞克、康托費茲傑拉。

Hey, guys. Thank you very much for taking my questions. I guess, one, in the IO-naive renal cell cancer setting, I understand AZ is running the study. But I guess what can you say about what the next step might be and the timing of a potential pivotal trial?

嘿，大家好。非常感謝您回答我的問題。我想，首先，在IO初治腎細胞癌領域，我了解到AZ正在進行這項研究。但我想您能透露下一步可能採取什麼措施以及潛在關鍵試驗的時間嗎？

Yes. So I'll comment there. We've agreed with AstraZeneca to not comment anything further than those initial plans, and we'll say more once the study shows up on clinicaltrials.gov.

是的。所以我會在那裡發表評論。我們已與阿斯特捷利康達成協議，除了初步計劃外，不會發表任何其他評論，一旦研究結果在 clinicaltrials.gov 上公佈，我們會透露更多資訊。

Okay. Understood. And I know you mentioned on the call, it sounds like you're looking to optimize the stat plan for the Phase 3 non-small cell lung for dom. Can you expand a little bit on that? What does that entail?

好的。明白了。我知道您在電話中提到，聽起來您正在尋求優化 DOM 的 3 期非小細胞肺的統計計劃。能稍微詳細說明一下嗎？這意味著什麼？

Yes. So my comment was more general than that. We make that point for all of our studies that we're continuously looking at the stat plans for all of our programs. Obviously, in the anti-TIGIT field, there's been changes made by others. There's been some comments or statements put forward from the ODAC with the FDA. So at this point, we're not making any changes, but we just wanted to acknowledge that we're always considering that possibility.

是的。所以我的評論比這更籠統。我們在所有研究中都強調這一點，我們會持續關注所有項目的統計計劃。顯然，在反TIGIT領域，其他人也做出了改變。ODAC 向 FDA 提出了一些評論或聲明。因此目前我們不會做出任何改變，但我們只是想承認我們一直在考慮這種可能性。

Okay. Got it. And maybe just last question. I wonder, if you can talk a little bit about the clinical benefit that you're seeing for stable disease patients from the cas study. And it seems like you got a decent number of them still on study. So I guess how clinically relevant is disease control for these patients?

好的。知道了。也許這只是最後一個問題。我想知道您是否可以談談您從 CAS 研究中看到的病情穩定的患者的臨床益處。看起來還有相當一部分問題仍在研究中。所以我猜測疾病控制對這些患者來說在臨床上有多大意義？

Yes. So this is Dimitry. I'll take the question. So it's very, very relevant for patients. Just imagine RECIST was determined based on large data sets, mostly for chemotherapy. There had been an effort to standardize assessments of treatment. And based on reproducibility, interobservariability, a threshold of 30% was set. I think everybody would agree whether or not you're at 25% or 35% depending on the tumor volume that is not really relevant. Having tumor that doesn't grow and that has gone down in tumor volume is very important.

是的。這就是 Dimitry。我來回答這個問題。所以這對患者來說非常非常重要。試想一下，RECIST 是根據大型資料集確定的，主要用於化療。人們一直在努力使治療評估標準化。並根據可重複性、可觀察性設定了30%的閾值。我認為每個人都會同意是否達到 25% 或 35% 取決於並不真正相關的腫瘤體積。腫瘤不再生長且體積縮小是非常重要的。

And then the other point that is more, let's say, from a regulatory perspective, response rate is never ever a registrational endpoint beyond accelerated approval. In this case, in kidney cancer, progression free survival is the relevant endpoint and everybody who does not progress contributes to that. And in a Kaplan-Meier estimate, the longer you are free of progression, meaning the longer your response is lasting or the longer your stable disease is lasting, contributes equally for each patient in the Kaplan-Meier estimate for progression free survival.

另一點是，從監管角度來看，回應率永遠不會成為加速批准之外的註冊終點。在這種情況下，對於腎癌而言，無惡化存活期是相關終點，且所有未進展的患者均對此有所貢獻。在 Kaplan-Meier 估計中，您無進展的時間越長，意味著您的反應持續時間越長或您的穩定疾病持續時間越長，對於 Kaplan-Meier 估計的無進展生存期中每個患者的貢獻都是相同的。

So both from a clinical perspective for patients and from a regulatory registrational perspective, they're very important. And from a registrational perspective, it is equally important as a response.

因此，無論從患者的臨床角度或從監管註冊的角度來看，它們都非常重要。從註冊的角度來看，它與回應同樣重要。

Okay, thank you.

好的，謝謝。

We'd like to be able to get to everybody. So if you have more than a couple of questions, can you please hop up and join the queue at a later point? That would be great. Thank you.

我們希望能夠幫助到每一個人。因此，如果您有多個問題，您可以稍後再加入隊列嗎？那太棒了。謝謝。

Jonathan Miller, Evercore ISI.

喬納森·米勒 (Jonathan Miller)，Evercore ISI。

Hi guys. Thanks for taking my question and reminding us to limit our questions just before I got my chance in the queue. Appreciate that. Can I start with some questions about him too, please? Can I start with some questions about HIF-2, please. I noticed in your prepared remarks, you talked about two unconfirmed PRs that could still confirm.

嗨，大家好。感謝您回答我的問題，並在我排隊之前提醒我們限制我們的提問數量。非常感謝。我可以先問一些關於他的問題嗎？我可以先問一些關於 HIF-2 的問題嗎？我注意到在您準備好的發言中，您談到了兩個尚未證實但仍可證實的 PR。

I'd really like to get some detailed color on that. We hear reports. There have been papers written that suggest that one of maybe, I think one of those two, based on how I'm counting, had a subsequent scan of stable disease.

我真的很想對此進行詳細的了解。我們聽取了報道。有論文表明，根據我的計算，也許這兩個人中的一個，我認為是其中一個，後續掃描顯示病情穩定。

So can you comment of those two unconfirmed partial responses that you're talking about, how many of those have not had a follow-up scan yet or might be expected to confirm based on one additional follow-up scan?

那麼，您能否對您所說的兩個未經證實的部分答覆進行評論，其中有多少尚未進行後續掃描或可能需要根據一次額外的後續掃描進行確認？

And maybe building off of that, given that a lot of the differentiation you're talking about compared to belzutifan is in the PD rate, i.e., at the first scan here, how well, early in the curves, how well do you anticipate that to translate to a better profile versus belzutifan in a combo setting, especially combos with drugs like TKIs, which give their benefits rapidly at those first couple of scans?

也許基於此，考慮到您所說的與 Belzutifan 相比的許多區別在於 PD 率，即在第一次掃描時，在曲線的早期，您預計在多大程度上這與 Belzutifan 的組合環境中相比具有更好的概況，尤其是與 TKI 等藥物的組合，這些藥物在最初幾次掃描中就能迅速發揮作用？

Yes. So the first question kind of take it because there's a lot of different questions in there. But maybe just to jump to the back part of your question as far as who has not had a follow-up scan yet that was a responder. There was one patient in the 100 mg cohort that has not had a follow-up scan yet and one patient in the 50 mg cohort.

是的。因此，第一個問題有點類似，因為其中有許多不同的問題。但也許只是跳到問題的後面部分，至於誰還沒有進行過後續掃描，那就是回應者。100 毫克組中有一名患者尚未接受後續掃描，50 毫克組中也有一名患者尚未接受後續掃描。

So their last scans show them as being responders for the first time and they are waiting for their confirmatory scans now. And then as we said for the 100 mg, there is one patient that did not confirm so far, only one patient. And in fact, as we mentioned in the script, out of all of the responders, every responder is still on treatment with the exception of that one patient that did not have a confirmed response in the 100 mg cohort. Did that answer your question? And we can go to the second part.

因此，他們最近的掃描結果首次顯示他們是回應者，現在他們正在等待確認掃描。正如我們所說的 100 毫克，到目前為止還有一名患者尚未確認，只有一名患者。事實上，正如我們在腳本中提到的那樣，在所有有反應的患者中，除了在 100 毫克組中沒有確認反應的一名患者外，每個有反應的患者仍在接受治療。這回答了你的問題嗎？我們可以進入第二部分。

Yes, I was thinking specifically of that 100 mg cohort. I'm just trying to count UPRs and trying to get a sense for where the ORR could realistically get to at the end of the day. And in that 100 mg cohort specifically?

是的，我特別想到了那 100 毫克的族群。我只是試著計算 UPR，並試圖了解 ORR 最終能夠實際達到什麼水平。具體來說是 100 毫克組嗎？

Yes. So 33% plus was the ORR. We said that one patient will not confirm. So that means the maximum confirmed ORR that we can get to, based on the current responders, so that's excluding stable disease patients that have also seen significant tumor reduction.

是的。因此 ORR 是 33% 以上。我們說有一個病人不會確認。因此，這意味著根據目前的反應，我們可以獲得最大確認的 ORR，因此這不包括病情穩定且腫瘤也顯著縮小的患者。

So there could be other stable disease patients that also contribute to the ORR. But based on the current responders, the maximum confirmed response rate we can get to is 31%. And then if just one of those pending responders confirm, then that would take the ORR to 28.3%.

因此可能還有其他病情穩定的患者也對 ORR 有所貢獻。但根據目前的響應者情況，我們可以獲得的最大確認回應率為 31%。然後，只要有一名待定回應者確認，那麼 ORR 就會達到 28.3%。

Great guys. And on--

很棒的傢伙。還有——

Yes, I can take the second part of the question about stable disease in the combination. So a few things. So of course, in the combination, we are going against cabo and we're building up on top of cabo. So everybody in the control arm would get cabo and we are doing the combination. If you think what the combination can do, it can actually help patients in different ways.

是的，我可以回答問題的第二部分，關於聯合治療中的穩定疾病。有幾件事。因此，當然，在組合中，我們將對抗 Cabo，並在 Cabo 之上進行建造。因此對照組中的每個人都會得到 cabo，我們正在進行組合。如果你思考一下這種組合能起到什麼作用，它實際上可以以不同的方式幫助患者。

On cas, we see both early responders. We have more than a few patients responding at the first scan at six weeks. We've also disclosed two patients now that responded respectively at 12 and 14 months. So that's something that goes on top of the TKI response rate.

在 CAS 上，我們看到了兩位早期響應者。我們有不少患者在六週後的第一次掃描中就有反應。我們也揭露，有兩名患者分別在 12 個月和 14 個月時出現反應。所以這是高於 TKI 回應率的。

The primary progression response rate for cabozantinib is about 20% or a little bit less and we hope to catch more patients from that 20% with a different mechanism for the combination. So of course, we can't speculate what it would be, but we, let's say, we would expect it to also improve on top of a TKI.

卡博替尼的原發性進展反應率約為 20％ 或略低，我們希望透過不同的聯合治療機制從這 20％ 中招募更多的患者。因此，我們當然無法推測它會是什麼，但我們可以說，我們預計它會在 TKI 的基礎上有所改善。

Sure. I guess, but I'm asking specifically about the comparison to the other HIF-2 here to belzutifan. If your differentiation from them is in PD rate or at least a lot of it is in PD rate, how will you be able to, would you be able to observe that differentiation in a combo setting where you have the TKI to pick up the slack on the first scan a little bit?

當然。我想是的，但我具體想問的是這裡其他 HIF-2 與 belzutifan 的比較。如果您與它們的區分在於 PD 率，或至少很大一部分在於 PD 率，那麼您如何能夠觀察到組合設定中的差異，在組合設定中，您可以使用 TKI 稍微彌補第一次掃描的不足？

So I'll comment there. I mean, again, you're purely speculating. But as you know, greater than 90% of those patients have some sort of HIF-2-driven component. And so there's absolutely still room to reduce the rate of primary progression. It puts more people into the queue, if you will. And I think that the place where you'll see that number of patients then leads into every other efficacy measure, whether it's ORR, PFS.

所以我會在那裡發表評論。我再說一遍，你純粹是在猜測。但如您所知，超過 90% 的患者都具有某種 HIF-2 驅動成分。因此，絕對仍有空間來降低原發性進展的速度。如果你願意的話，它會讓更多的人排隊。我認為，患者數量會影響到其他所有療效指標，無論是 ORR 還是 PFS。

And I have to say there's no reason to not start to think about why you may not see advantages in OS, even though that's not the approvable endpoint at this stage. There's nothing intrinsic about clear cell RCC that should suggest that you couldn't start to prolong OS as well.

我必須說，沒有理由不開始思考為什麼你可能看不到作業系統的優勢，即使這不是現階段可批准的終點。透明細胞 RCC 並沒有任何內在因素表明您無法開始延長 OS。

Thank you.

謝謝。

Thanks John.

謝謝約翰。

Peter Lawson, Barclays.

巴克萊銀行的彼得勞森 (Peter Lawson)。

Great. Thank you. Just a couple of follow-ups on the opt-in. Kind of what drives that decision for Gilead between this year and next year? Is there something from your side, their side? Or is there a different data cut? And then if Gilead doesn't opt in, what are the next steps?

偉大的。謝謝。只需對選擇加入進行一些後續跟進。是什麼促使吉利德在今年和明年之間做出這項決定的？您那邊和他們那邊有什麼事嗎？或有不同的數據截斷？那麼，如果吉利德不選擇加入，下一步該怎麼辦？

Yes. So I'll take that. First of all, there's nothing specifically driving it other than how long they take to make a decision. It happens to be that because of when we're delivering it, it's relatively near the end of the year. They have a certain amount of time that could, in fact, creep into next year. It doesn't necessarily creep into next year. So that's the only component why we introduced that ambiguity in laying out a time frame. As you know, they could opt in yesterday if they want it. So that's, it sort of defines the latest point of when they can opt in.

是的。所以我會接受。首先，除了他們花多長時間做決定之外，沒有什麼特別的因素來驅動它。恰巧，由於我們交貨的時間比較接近年底。他們有一定的時間，事實上，這個時間可能會延續到明年。這並不一定會延續到明年。所以這是我們在製定時間框架時引入模糊性的唯一因素。如你所知，如果他們願意的話，昨天他們就可以選擇加入。所以，這在某種程度上定義了他們可以選擇加入的最晚時間點。

The second question, right. If they don't opt in, there's not necessarily anything that we would do immediately, but it could be any of the three things that you might think of. We're very comfortable continuing with this one on our own. We love the program. I think it's a great opportunity.

第二個問題，對的。如果他們不選擇加入，我們不一定會立即採取任何行動，但可能是您能想到的三件事中的任何一件。我們非常樂意獨自繼續進行這項工作。我們很喜歡這個節目。我認為這是一個很好的機會。

Secondarily, we've already had plenty of inbound interest from others who recognize that there is an opt-in decision. I think most other companies have expressed that the thought that they think Gilead would opt in, but we could consider partnership with another company as well. Bob?

其次，我們已經收到了大量來自其他人的興趣，他們認識到存在選擇加入的決定。我認為大多數其他公司都表示他們認為吉利德會選擇加入，但我們也可以考慮與其他公司合作。鮑伯？

Just on the economics, Peter, so it's $150 million opt-in fee should they decide to opt in and then we share costs 50, 50 on the program going forward. And then I don't know if you were getting at this with your question, but obviously, if Gilead were to opt in, then we'd work through the details of any additional studies we might want to add to our clinical development plan together.

彼得，僅從經濟角度考慮，如果他們決定加入，那麼選擇費就是 1.5 億美元，然後我們在未來以 50% 的比例分攤計劃成本。然後我不知道你的問題是否涉及了這一點，但顯然，如果吉利德選擇加入，那麼我們將共同研究我們可能想要添加到我們的臨床開發計劃中的任何其他研究的細節。

Great. Thanks so much.

偉大的。非常感謝。

Asthika Goonewardene, Truist Securities.

Asthika Goonewardene，Truist Securities。

Hey guys, thanks for taking my question. I'm going to repeat what Jon did and ask a multipart single question here. So on volrustomig plus casdatifan, when you think ahead as the right comp for maybe some sort of a pivotal study down the line, what do you think the right comp is? And I ask because nivo-ipi mix is the most logical comp but obviously a very high bar.

嘿夥計們，謝謝你們回答我的問題。我將重複喬恩所做的事情並在這裡提出一個由多部分組成的單一問題。因此，在 volrustomig plus casdatifan 上，當您提前考慮未來某種關鍵研究的正確補償時，您認為正確的補償是什麼？我之所以問這個問題，是因為 nivo-ipi 組合是最合乎邏輯的組合，但顯然標準非常高。

And related, the durable CR rate with nivo-ipi is something that is quite attractive about that combination in RCC. So how important is it for you to kind of replicate that or beat that specific endpoint, adjacent to the regular primary endpoints that you would consider?

與此相關的是，nivo-ipi 的持久 CR 率是 RCC 中該組合相當有吸引力的地方。那麼，對於您來說，複製或擊敗該特定終點（與您考慮的常規主要終點相鄰）有多重要？

Yes. So this is Dmitry. I can take the question. So the relevant benchmark would be the CheckMate-214 study, although, of course, that is now somewhat outdated. But I think with the mature follow-up, the data has held up very well.

是的。這就是德米特里。我可以回答這個問題。因此相關的基準是 CheckMate-214 研究，儘管現在這項研究已經有些過時了。但我認為，隨著後續工作的成熟，數據已經保持得很好。

We are building up on the bispecific, meaning the data for volru has been presented last year at ESMO in kidney cancer. And I think most people objectively would agree it looks at least as good or perhaps a little bit better than ipi-nivo. Some of the toxicity is a little bit better. So we don't expect, let's say, to have to beat ipi-nivo with cas alone. We know we have a solid CTLA-4 PD-1 backbone and then build on top of that.

我們正在研究雙特異性抗體，這意味著 volru 的數據已在去年在 ESMO 腎癌研究中發表。我認為大多數人都會客觀地認為它看起來至少和 ipi-nivo 一樣好，或者可能更好一點。有些毒性稍微好一點。所以我們不期望僅憑 cas 就能擊敗 ipi-nivo。我們知道我們擁有堅實的 CTLA-4 PD-1 主幹，並在此基礎上進行建置。

The CR rate, indeed, the durable, or you say, the durable response rate is important. Obviously, we don't completely know, but I think it's reasonable to hypothesize that, let's say, one of the things for ipi-nivo is the (inaudible) PD rate investigators typically will not use ipi-nivo in the setting where they really need a fast response for a patient. So that's something we might be able to change.

CR 率，實際上，持久性，或您說的持久回應率很重要。顯然，我們並不完全了解，但我認為可以合理地假設，比如說，ipi-nivo 的其中一個特點是（聽不清楚） PD 率研究人員通常不會在真正需要對患者進行快速反應的情況下使用 ipi-nivo。所以我們也許能夠改變這一點。

We might be able to get a lower primary PD rate when we build up on it. And every other benchmark, we expect to be able to deepen or lengthen, meaning longer duration of response because we add a mechanism that really helps out in the long term, longer progression free survival and hopefully longer overall survival as well.

當我們在此基礎上進一步發展時，我們可能能夠獲得更低的初級 PD 率。對於其他所有基準，我們期望能夠深化或延長，這意味著更長的反應持續時間，因為我們添加了一種真正有助於長期的機制，更長的無進展生存期，並希望更長的總體生存期。

Yes. And I think just to hit on the primary PD point, like that was, I think, what got AstraZeneca very interested is that you do have 25% of patients that just flow right through ipi-nivo. And so by adding a drug that seems to have a relatively low primary PD, we think we can especially improve that front end of the PFS curve.

是的。我認為，只是為了觸及主要的 PD 點，就像那樣，我認為，讓阿斯特捷利康非常感興趣的是，確實有 25% 的患者直接透過 ipi-nivo 治療。因此，透過添加一種似乎具有相對較低的原發性 PD 的藥物，我們認為我們可以特別改善 PFS 曲線的前端。

Yes. And then lastly, to add on top of that, also the safety profile for HIF-2 targeting specifically casdatifan would be far more favorable than adding a TKI on top of that regimen. So that's what we refer to the TKI-sparing approach because first-line patients can be on treatment for a very long time, which is cumbersome and, let's say, a burden on patients if they have to stay on a TKI for a long time.

是的。最後，補充一點，針對 HIF-2 的卡達替芬的安全性也將比在該方案上添加 TKI 更為有利。這就是我們所謂的 TKI 節約方法，因為第一線患者可能需要接受很長時間的治療，如果患者必須長期使用 TKI，這會很麻煩，甚至可以說是一種負擔。

Great. Thanks so much guys.

偉大的。非常感謝大家。

Thank you.

謝謝。

Daina Graybosch, Leerink Partners.

Daina Graybosch，Leerink Partners。

I'm going to follow up right along with what Asthika just asked about the trial conduct for both PEAK-1, the combo with cabo and the combo with the CTLA-4 bispecific. And that we've seen in RCC that keeping patients on study seems to be really important that if you have any toxicities in managing those discontinuations can really drive the primary efficacy endpoints.

我將立即跟進 Asthika 剛才詢問的有關 PEAK-1、與 cabo 的組合以及與 CTLA-4 雙特異性的組合的試驗情況。我們在 RCC 中看到，讓患者繼續接受研究似乎非常重要，如果在管理這些停藥過程中出現任何毒性，那麼確實可以推動主要療效終點。

Can you talk through your strategy in both of those trials to manage treatment exposure, particularly as you started with the 60 mg dose of cabo? And they haven't always done that in our combination studies? And then also what you're doing with Astra to manage talks with a pretty toxic anti-CTLA-4 as well?

您能否談談在這兩次試驗中管理治療暴露的策略，特別是當您開始使用 60 毫克劑量的卡波時？在我們的組合研究中他們並不總是這樣做嗎？那麼，您還與 Astra 一起採取了哪些措施來應對具有相當毒性的抗 CTLA-4 藥物的談判？

Yes. So I'll start with the cas combination. So good points. I see it as a benefit that we will be starting with 60. The trials where the TKI, in this case, cabo wasn't started at full dose was based on toxicities identified with the combination. And therefore, you give up on some early higher exposure for an active agent like cabo. So I think it's important for people to be able to start at full dose.

是的。因此我將從 cas 組合開始。非常好的觀點。我認為從 60 開始是一個好處。在本例中，TKI 試驗中未以全劑量開始使用卡波是基於已發現的組合毒性。因此，您放棄了使用 cabo 等活性劑的早期更高曝光率。因此我認為人們能夠開始服用全劑量藥物非常重要。

That's the safety data we are generating right now. We already have generated a lot of experience with cas by itself and how investigators manage the toxicity. I think the data that we've shown is very convincing that we have virtually no one discontinuing the drug for toxicity. We have some interruptions and people are able to manage the toxicities and then stay on. So that's the experience we'll also use for the combination.

這就是我們現在正在產生的安全資料。我們已經累積了豐富的 CAS 本身以及研究人員如何管理毒性的經驗。我認為我們所展示的數據非常有說服力，幾乎沒有人因為毒性而停止使用該藥物。我們遇到了一些幹擾，但人們能夠控制毒性然後繼續留下來。我們也將利用這些經驗來進行組合。

The other thing that makes it a little bit easier in giving guidance is the specific profiles for toxicity for both cas and for cabo are, let's say, cabo, of course, very well-known and cas relatively straightforward with anemia and hypoxia, no relevant overlapping toxicity.

另一件使提供指導變得更容易的事情是，cas 和 cabo 的毒性具體情況是，當然，cabo 非常知名，而 cas 相對簡單，伴隨貧血和缺氧，沒有相關的重疊毒性。

So giving guidance on potential dose reductions will be straightforward and to make it as clean as possible that the trial is what we call an active comparator placebo-controlled trial. So people on the control arm will be getting cabo plus placebo to take out all bias from investigator and patients on the assessment of the AE profile.

因此，就潛在的劑量減少提供指導將非常直接，並儘可能清楚地表明該試驗是我們所說的活性對照安慰劑對照試驗。因此，對照組的受試者將服用 Cabo 加安慰劑，以消除研究人員和患者對 AE 概況評估的所有偏見。

When it comes to AstraZeneca, we can't comment as much on that trial. Obviously, that's currently in start-up and is led by AstraZeneca. Our colleagues at AstraZeneca have generated quite a bit of safety data. Some of that is in the public domain, as I referred to from ESMO 2023, and there's a lot more data that's not in the public domain.

談到阿斯特捷利康，我們無法對該試驗發表太多評論。顯然，該計畫目前處於啟動階段，由阿斯特捷利康主導。我們阿斯特捷利康的同事已經產生了相當多的安全資料。正如我在 ESMO 2023 中提到的，其中一些屬於公共領域，但還有很多數據不屬於公共領域。

And with that, they've, let's say, generated a lot of experience in giving specific guidance and the toxicities they seeing are, they are seeing, of course, are not new. Ipi-nivo has been on the market for quite a while and kidney cancer investigators are, let's say, very well aware and very experienced with the management of the toxicity profile of ipi-nivo. And again, the lack of overlapping toxicities will make it easier to give specific guidance for each agent.

由此，他們在提供具體指導方面累積了豐富的經驗，而他們所看到的毒性當然並不是什麼新鮮事。Ipi-nivo 已經上市很長一段時間了，腎癌研究人員對 ipi-nivo 毒性特徵的管理非常了解，並且經驗豐富。而且，缺乏重疊毒性將使得針對每種藥物提供具體指導變得更加容易。

Salveen Richter, Goldman Sachs.

高盛的薩爾文·里希特（Salveen Richter）。

Hey, this is Mark on for Salveen. We have a question on TIGIT and lung on the ARC-10 data at SITC. It looks clear that TIGIT is adding a survival benefit, but why do you think the benefit on ORR is less clear? And also, how do you expect this data to translate to the STAR-121 study where it seems like OS benefit from the dom-zim doublet is likely already above KEYTRUDA chemo combo? And when should we expect to see initial data from the STAR-121? Is it possible that we could see it in the second half of 2025? Thanks.

嘿，我是 Salveen 的馬克。我們對 SITC 的 ARC-10 數據中的 TIGIT 和肺有疑問。很明顯，TIGIT 增加了生存益處，但您為什麼認為 ORR 的益處不太明顯？此外，您期望這些數據如何轉化為 STAR-121 研究，其中似乎 dom-zim 雙聯療法的 OS 益處可能已經高於 KEYTRUDA 化療組合？我們什麼時候可以看到 STAR-121 的初始資料？我們有可能在 2025 年下半年看到它嗎？謝謝。

So let me start. I think that, well, your first question was about ORR. We think the ORR, there was a quite reasonable improvement. Keep in mind, this is immunotherapy, and it comes up time and time again. The place where you're really getting your benefit is an enhancement of OS and its durability, it's the tail. And that's why it's a profound signal that we're seeing.

那麼就讓我開始吧。我認為，您的第一個問題是關於 ORR 的。我們認為 ORR 有了相當合理的改善。請記住，這是免疫療法，而且它會一次又一次地出現。您真正獲得好處的地方是操作系統及其耐用性的增強，即尾部。這就是我們看到的深刻訊號的原因。

ORR is better, but what you really should be focused on, the world uses ORR as a surrogate for PFS as a surrogate for OS. And the reason we're out at two plus years and we have the OS data is that that's what you're really looking at. But nonetheless, we don't think there's anything unusual about the advantage on ORR. The second question that you asked was?

ORR 更好，但你真正應該關注的是，世界使用 ORR 作為 PFS 的替代品，作為 OS 的替代品。我們之所以會花兩年多的時間並且擁有 OS 數據，是因為這就是您真正要關注的。但儘管如此，我們認為 ORR 的優勢並沒有什麼不尋常的。你問的第二個問題是？

How do you expect this to translate the (inaudible)?

你希望這將如何翻譯（聽不清楚）？

So we think the translation, we've already seen in EDGE-Gastric an advantage on top of chemo. The thing that, this is where we think we actually have a huge advantage. When we think about the STAR-121, while we stopped ARC-10 for strategic reasons, say, just on an evolving market that physicians are moving more and more from just using KEYTRUDA to using KEYTRUDA plus chemo, even in high PD-L1.

因此我們認為，我們已經看到了 EDGE-Gastric 比化療更有優勢。我們認為，我們實際上在這方面具有巨大優勢。當我們考慮 STAR-121 時，我們出於戰略原因停止了 ARC-10，比如說，在一個不斷發展的市場中，醫生越來越多地從僅使用 KEYTRUDA 轉向使用 KEYTRUDA 加化療，即使在高 PD-L1 中也是如此。

What's become very apparent is that the Fc-enabled anti-TIGITs have an issue with AEs in the context of chemo. So we feel like we're well positioned to even have a stronger advantage relative to any of the competitors at this point in that population.

非常明顯的是，Fc 支持的抗 TIGIT 在化療方面有 AE 問題。因此，我們覺得，我們處於有利地位，甚至比該群體中的任何競爭對手都具有更大的優勢。

Now the second piece is just from a scientific standpoint. The underlying mechanism is that anti-TIGIT is enhancing the activity of the anti-PD-1. Same phenomena that we demonstrated in the context of GI cancers on top of chemo, and we've shown the data from EDGE-Gastric, and we think that same thing will hold up there. And then the particular advantage is that when you add dom on top of the anti-PD-1 chemo, what we're seeing consistently again is that we're not seeing any enhanced AEs. So you really get the full advantage of what the mechanism offers with the Fc silent molecule.

第二部分只是從科學的角度來看。其潛在機制是抗 TIGIT 增強了抗 PD-1 的活性。我們在化療基礎上治療胃腸道癌症的背景下證明了同樣的現象，並且我們展示了來自 EDGE-Gastric 的數據，我們認為同樣的現象將在那裡得到證實。特別的優點是，當你在抗 PD-1 化療之上添加 dom 時，我們再次一致看到的是，我們沒有看到任何增強的 AE。因此，您真正能夠充分利用 Fc 沉默分子機制的優勢。

I think it's an important step to realize there's enough data out there to just bucket into two categories, the Fc-enabled and the Fc silent. So AstraZeneca and us and all the other later-stage molecules are having issues consistently with those immune-associated adverse events.

我認為，認識到有足夠的數據可以將其分為兩類，即支持 Fc 的和靜音的 Fc，這是很重要的一步。因此，阿斯特捷利康和我們以及所有其他後期分子都在持續遇到與免疫相關的不良事件的問題。

And then your next question was when might we see. We haven't commented yet. The point that I would raise is that in the context of EDGE-Gastric, which was fully enrolled, I'm sorry, so our STAR-221, which is the Phase 3 correlate to that, the OS for the standard of care is about 13 months. As you know, in non-small cell lung, there it's going to be over 20 months. And so we'll give guidance on readout sometime next year.

然後你的下一個問題是，我們什麼時候可以看到。我們尚未發表評論。我想提出的觀點是，在 EDGE-Gastric 的背景下，該研究已經完全招募了患者，很抱歉，所以我們的 STAR-221（與之相關的第 3 階段）標準治療的 OS 約為 13 個月。如您所知，對於非小細胞肺而言，這一時間將超過 20 個月。因此，我們將在明年某個時候提供讀數指導。

Sounds good. Thank you.

聽起來不錯。謝謝。

Thank you.

謝謝。

Jason Zemansky, Bank of America.

美國銀行的傑森·澤曼斯基（Jason Zemansky）。

Good evening. Thank you so much for taking our questions and congratulations on both the quarter and the recent presentations. I had a couple of quick follow-ups on the PEAK-1 study. In terms of primary endpoint, you have PFS.

晚安.非常感謝您回答我們的問題，並祝賀本季度和最近的演示。我對 PEAK-1 研究進行了一些快速追蹤。就主要終點而言，您有 PFS。

Merck is advancing a number of similar studies with belzutifan, with lenvatinib in a couple of different settings, including second line, where the primary endpoint is PFS and OS. Just curious on kind of the decision behind making the primary endpoint PFS.

默克公司正在推動多項與貝祖替凡類似的研究，並在幾種不同的環境中使用侖伐替尼，包括二線治療，其主要終點是 PFS 和 OS。只是好奇制定主要終點 PFS 背後的決定是什麼。

And then just kind of fundamentally, what do you think you need to do to distinguish yourself from Merck's combinations given their potential to kind of that first-mover advantage, particularly when if you look at, say, the first-line setting, there are a range of different studies that you might not have the same sort of efficacy, but kind of that inertia there keeps them well used. Example, KEYNOTE-426 looks like 17% still use it even though it's maybe not as good. It's a CheckMate-214 or CheckMate-9ER. Thanks.

那麼從根本上來說，考慮到默克的組合療法具有先發優勢的潛力，您認為需要做些什麼才能將自己與默克的組合療法區分開來，特別是當您查看一線治療環境時，有一系列不同的研究可能沒有相同的功效，但這種慣性使它們能夠得到很好的使用。例如，KEYNOTE-426 看起來仍有 17% 的人在使用它，儘管它可能不那麼好。它是 CheckMate-214 或 CheckMate-9ER。謝謝。

Yes. So when it comes to treatment preferences, that's the last part of your question. That has a lot of things that go into it. I actually referred to that earlier on. Ipi-nivo, for example, is very well recognized for very durable responses and long-term survival benefit. The downside of this regimen is recognized as primary progression.

是的。所以關於治療偏好，這是你問題的最後一部分。這裡面牽涉很多東西。我實際上之前就提到過這一點。例如，Ipi-nivo 因其非常持久的反應和長期生存益處而廣受認可。這種療法的缺點被認為是原發性進展。

So patients with bulky disease, patients who need a response immediately, they're typically not put on ipi-nivo. And based on early readouts, patients with favorable risk were also not given the opportunity. But with longer-term follow-up, it's now very consistent that the IDMC risk categories are no longer considered to be predictive of ipi-nivo benefit. So that's one of the reasons.

因此，患有重大疾病的患者、需要立即治療的患者通常不會使用 ipi-nivo。且根據早期讀數，具有有利風險的患者也沒有獲得機會。但經過長期的跟踪，現在非常一致的是，IDMC 風險類別不再被認為可以預測 ipi-nivo 的益處。這就是原因之一。

When it comes to differentiation, it's the question I answered previously. I think in this particular setting, Merck is not doing this trial. They don't have a TKI free first-line trial, which from a physician-patient perspective, not having the TKI toxicity for the long duration of treatment in the first line by itself is already a very important differentiator.

說到差異化，這是我之前回答過的問題。我認為在這種特殊情況下，默克公司不會進行這項試驗。他們沒有進行 TKI 免費第一線試驗，從醫病角度來看，在第一線治療中長期治療沒有 TKI 毒性本身已經是一個非常重要的區別因素。

When it comes to the second-line differentiation, PEAK-1 versus LITESPARK-11, having a far more preferred TKI as combination partner, cabo versus lenva, the logical choice because Merck owns lenva or part of it, for us is a major benefit. We consistently hear from physicians that cabo is much easier to handle than lenvatinib. The dosing complexity of multiple dose levels for lenvatinib, the overall less, let's say, less well-perceived toxicity profile is an important differentiator.

當談到二線差異時，PEAK-1 與 LITESPARK-11，擁有更受歡迎的 TKI 作為組合夥伴，cabo 與 lenva，這是合乎邏輯的選擇，因為默克擁有 lenva 或它的一部分，這對我們來說是一個重大的好處。我們常聽醫生說卡波比崙伐替尼更容易處理。侖伐替尼多劑量水平的給藥複雜性、整體較少的（可以說不太為人所知的）毒性特徵是一個重要的區別因素。

The other differentiator we have is even though Merck was earlier with the trial that comes with the downside that their experience in post-adjuvant patients by definition will be very limited to almost not existing. We will be able to capture those patients. So potentially, we will get a broader label as well.

我們面臨的另一個差異是，儘管默克公司較早進行了該試驗，但其缺點是，從定義上講，他們在輔助治療後患者中的經驗非常有限，幾乎為零。我們將能夠捕獲這些病人。因此我們也有可能獲得更廣泛的標籤。

And then the last part of your question about the dual primary endpoint, I cannot comment on why Merck is doing it. I can only speculate. The registrational endpoint is PFS. Whether or not OS is a well powered secondary endpoint or a primary endpoint comes a little bit down to trial size efficiency. However, the only reason to do OS as co-primary or better saying dual primary endpoint is if you are not sure if you can hit PFS.

然後關於你問題的最後一部分關於雙重主要終點，我無法評論默克公司為什麼這樣做。我只能推測。註冊端點是 PFS。作業系統是否為功能強大的次要端點或主要端點，在一定程度上取決於試驗規模的效率。然而，將 OS 作為共同主要終點或更好地說是雙主要終點的唯一原因是如果您不確定是否可以達到 PFS。

So if you hit PFS as primary endpoint, only the alpha goes to the secondary endpoint and you have an adequately powered overall survival analysis. So in my, let's say, from my perspective, doing it as a dual primary endpoint unnecessarily makes the trial larger, but they might have done it because they didn't know what the trial readout would be. Obviously, we will have that advantage that the trial that they are doing will have read out before we get to our analysis. And in a rare case that we would have to make updates, we can do so.

因此，如果您將 PFS 作為主要終點，則只有 alpha 會轉到次要終點，並且您擁有足夠強大的總體存活分析。因此，從我的角度來看，將其作為雙重主要終點不必要地使試驗規模更大，但他們這樣做可能是因為他們不知道試驗讀數會是什麼。顯然，我們的優勢在於，在我們進行分析之前，他們所做的試驗就已經讀出來了。在極少數情況下，我們需要進行更新，我們可以這樣做。

Got it. So if I'm hearing you correctly, you think between PEAK-1 and LITESPARK-011, you'll have a tolerability edge. Do you think you can also have an efficacy edge as well?

知道了。所以如果我沒聽錯的話，您認為在 PEAK-1 和 LITESPARK-011 之間，您將具有可容忍度優勢。您認為您也可以擁有功效優勢嗎？

Absolutely. If you, let's say, if I just start with the low bar, if you can stay on a TKI longer because it's better tolerated, you have more benefit. Then, of course, we are generating the cas data that starts to look differentiated from belzutifan on efficacy. Notably the primary PD rate, but also other benchmarks that start, or other metrics that start to look better. So we are confident that both the combination partner, but also our HIF-2 alpha inhibitor, both will be part of the story of a better efficacy and a better safety profile combined.

絕對地。比如說，如果我從低標準開始，如果您能夠繼續使用 TKI 更長時間，因為它的耐受性更好，那麼您將獲得更多益處。然後，當然，我們正在產生 cas 數據，其在功效上開始與 belzutifan 有所區別。值得注意的是主要的 PD 率，但也有其他基準開始發揮作用，或者其他指標開始變得更好。因此，我們相信，組合藥物和我們的 HIF-2 阿爾法抑制劑都將實現更佳的療效和更佳的安全性。

Perfect. Thanks for the color.

完美的。謝謝你的顏色。

Eva Fortea-Verdejo, Wells Fargo Securities.

伊娃‧福蒂亞-維德霍 (Eva Fortea-Verdejo)，富國證券。

Hi. Thanks for taking our question and congrats on the progress. A quick one from us. So for the dom zim combo in the Phase 2 EDGE-Gastric, you guided to OS data in 2025. So if I recall correctly, you've only shown data for one arm, but the study included more arms. So I was wondering if you're going to share data from the other arms together in the same update or if this might come at a later time next year? Thanks.

你好。感謝您回答我們的問題，並對所取得的進展表示祝賀。我們快速說一句。因此，對於第 2 階段 EDGE-Gastric 中的 dom zim 組合，您將在 2025 年指導 OS 資料。所以如果我沒記錯的話，你只展示了一個組的數據，但這項研究包括了更多的組。所以我想知道您是否會在同一更新中分享來自其他部門的數據，或者這是否會在明年晚些時候出現？謝謝。

So the guidance indeed is correct. We have committed to the OS data for EDGE-Gastric that's maturing right now for 2025. I think we've said it before, the enrollment in arm A1, that's the arm we presented, and then A2 is the contribution of component arm for regulatory purposes was not at the same time. They were done sequentially.

所以這個指導確實是正確的。我們承諾為 2025 年提供 EDGE-Gastric 的 OS 數據，目前已成熟。我想我們之前已經說過了，A1 組的註冊，這是我們提出的組，然後 A2 是組成組的貢獻，出於監管目的，它們並不是同時進行的。它們是按順序完成的。

The data are maturing. And I would say it's unlikely we will present it all at the same time because these things don't mature at the same time. But at some point, we will present the data if it's mature.

數據日趨成熟。我想說，我們不太可能同時展示所有這些，因為這些東西不會同時成熟。但如果數據成熟了，我們就會呈現給大家。

Yigal Nochomovitz, Citi.

花旗的 Yigal Nochomovitz。

Yeah, hi. Thanks for the follow up. Just very quickly. I think, Terry, you mentioned in the prepared remarks that you may be in a position to provide updates in the more near term. Does that mean that you might get some of this data that's referenced in the release in this year? Or can you just clarify what you meant there? Thank you.

是的，你好。感謝您的跟進。非常快。特里，我想，你在準備好的發言中提到，你可能能夠在近期內提供最新消息。這是否意味著您可能會獲得今年發布中引用的一些數據？或者你能解釋一下你的意思嗎？謝謝。

Yes, we didn't want to get too specific, but let's recognize, look at all those studies we have ongoing. So we, or cohorts within the study. So we have a 150-milligram cohort. We have 100 milligram cabo. We have the 50 and 100 that we've already talked about that are continuing to mature. And what we felt is for sake of transparency and the importance of these data that when we see something meaningful, we're going to look to find a way to get it out there.

是的，我們不想說得太具體，但讓我們認識到，看看我們正在進行的所有這些研究。所以我們，或是研究內的群體。因此，我們有一個 150 毫克的隊列。我們有100毫克的卡波。我們已經討論過的 50 和 100 個項目正在不斷成熟。我們認為，為了透明度和這些數據的重要性，當我們看到有意義的東西時，我們會尋找一種方法來將其傳播出去。

But right now, we don't have any specific plans, but we recognize there's such a large volume of data we see that are interesting. We want to make sure we take the opportunity to update whenever it might be meaningful.

但目前，我們沒有任何具體的計劃，但我們認識到我們看到的大量數據都很有趣。我們希望確保抓住機會，在有意義的時候進行更新。

All right. Thank you. Got it.

好的。謝謝。知道了。

Thank you. There are currently no other questions in queue. This concludes today's conference call. Thank you for your participation. You may now disconnect your line.

謝謝。目前隊列中沒有其他問題。今天的電話會議到此結束。感謝您的參與。現在您可以斷開線路了。

Thank you.

謝謝。

Goodbye.

再見。