Exelixis Inc (EXEL) 2024 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Exelixis fourth quarter and fiscal year 2024 financial results conference call. My name is Sherry, and I'll be your operator for today. (Operator Instructions)

女士們、先生們，大家好，歡迎參加 Exelixis 第四季和 2024 財年財務業績電話會議。我叫雪莉，今天我將擔任您的接線生。（操作員指令）

As a reminder, this call is being recorded for replay purposes. I would now like to turn the call over to your host for today, Ms. Susan Hubbard, Executive Vice President of Public Affairs and Investor Relations. Please proceed.

提醒一下，本次通話正在錄音，以便重播。現在，我想將電話轉給今天的主持人、公共事務和投資者關係執行副總裁蘇珊·哈伯德女士。請繼續。

Thank you, Sherry, and thank you all for joining us for the Exelixis fourth quarter and fiscal year 2024 financial results conference call. Joining me are Michael Morrissey, our President and CEO; and Chris Senner, our Chief Financial Officer; who will review our progress for the fourth quarter and fiscal year 2024 ended January 3, 2025.

謝謝你，雪莉，也謝謝大家參加 Exelixis 第四季和 2024 財年財務業績電話會議。和我一起出席的還有我們的總裁兼執行長 Michael Morrissey；以及我們的財務長 Chris Senner；他們將審查我們截至 2025 年 1 月 3 日的第四季和 2024 財年的進展。

P.J. Haley, our Executive Vice President of Commercial; Amy Peterson, our Chief Medical Officer; and Dana Aftab, our Chief Scientific Officer are also on the call today and will participate in the Q&A portion of the call.

P.J. Haley，我們的商業執行副總裁；我們的首席醫療官艾米·彼得森 (Amy Peterson)；和我們的首席科學官 Dana Aftab 今天也將參加電話會議，並將參與電話會議的問答部分。

During the call today, we will refer to financial measures not calculated according to generally accepted accounting principles. Please refer to today's press release, which is posted on our website for an explanation of our reasons for using such non-GAAP measures as well as tables deriving these measures from our GAAP results.

在今天的電話會議中，我們將參考未依照公認會計原則計算的財務指標。請參閱我們網站上發布的今天的新聞稿，其中解釋了我們使用此類非 GAAP 指標的原因以及從我們的 GAAP 結果中得出這些指標的表格。

During the course of this presentation, we will be making forward-looking statements regarding future events and the future performance of the company. This includes statements about possible developments regarding discovery, product development, regulatory, commercial, financial, and strategic matters. Actual events or results could, of course, differ materially.

在本次演示過程中，我們將對未來事件和公司未來表現做出前瞻性陳述。這包括有關發現、產品開發、監管、商業、財務和策略事務的可能發展的聲明。當然，實際事件或結果可能會有重大差異。

We refer you to the documents we file from time to time with the SEC, which under the heading Risk Factors, identify important factors that could cause our actual results to differ materially from those expressed by the company verbally and in writing today, including, without limitation, risks and uncertainties related to product commercial success, market competition, regulatory review and approval processes, conducting clinical trials, compliance with applicable regulatory requirements, our dependence on collaboration partners and the level of cost associated with discovery, product development, business development, and commercialization activities.

請您參閱我們不時向美國證券交易委員會提交的文件，這些文件在「風險因素」標題下列出了可能導致我們的實際結果與公司今天口頭和書面表達的結果存在重大差異的重要因素，包括但不限於與產品商業成功、市場競爭、監管審查和批准流程、進行臨床試驗、遵守適用的監管要求、我們對合作夥伴的依賴以及與發現、開發

And with that, I will turn the call over to Mike.

說完這些，我將把電話轉給麥克。

All right. Thank you, Susan, and thanks to everyone for joining us on the call today. Exelixis had a breakout year in 2024, and we're already sprinting into 2025 after a busy January, where we provided important updates across all components of our business. Exelixis has built significant momentum to establish a multi-compound, multi-franchise oncology business, as we advance our cabozantinib, zanzalintinib, and early pipeline priorities to meet our aspirational revenue goals of $3 billion for cabo in 2030, and $5 billion for zanza in 2033.

好的。謝謝你，蘇珊，也謝謝大家今天參加我們的電話會議。Exelixis 在 2024 年取得了突破，在度過了忙碌的一月之後，我們已經開始衝刺 2025 年，在這一年，我們為業務的所有組成部分提供了重要更新。隨著我們推進卡博替尼、贊扎林替尼和早期管線優先事項以實現我們期望的收入目標（即 2030 年卡博的收入達到 30 億美元、2033 年贊扎的收入達到 50 億美元），Exelixis 已經建立了強大的發展勢頭來建立多化合物、多特許經營的腫瘤學業務。

We're thrilled to see continued growth and momentum of the cabo franchise in the US and globally, both in terms of absolute revenue and relative growth compared to the competition, and we expect to see additional upside with potential new indications.

我們很高興看到 Cabo 特許經營權在美國和全球範圍內持續增長並保持良好勢頭，無論是絕對收入還是與競爭對手相比的相對增長，我們預計隨著潛在的新跡像出現，還會看到額外的上升空間。

We outlined important news and priorities to jump start 2025 at our corporate update in January at the J.P. Morgan Healthcare Conference. I won't reiterate everything here today, but just focus on the top highlights, including, first, we saw a strong performance of the cabozantinib business in the fourth quarter and full year 2024 with approximate 11% growth in demand, new starts and revenue.

我們在 1 月摩根大通醫療保健會議的公司更新中概述了 2025 年開始的重要新聞和優先事項。今天我不會在這裡重複所有內容，而只關注最重要的亮點，首先，我們看到卡博替尼業務在第四季度和 2024 年全年表現強勁，需求、新開工和收入增長約 11%。

CABOMETYX maintained its status as the leading TKI for RCC in both the frontline IO TKI market and the second-line monotherapy segment.

CABOMETYX 在第一線 IO TKI 市場和第二線單藥治療領域均維持了 RCC 領先 TKI 的地位。

Fourth quarter 2024, US cabo franchise net product revenues grew 20% year over year to $515 million compared to fourth quarter 2023. Full year 2024, US cabo franchise net product revenues grew 11% to $1.81 billion compared to full year 2023. Continuing its role as the worldwide leading TKI, global cabo franchise net product revenues generated by Exelixis and its partners were approximately $690 million and $2.5 billion in the fourth quarter and full year 2024, respectively.

2024 年第四季度，美國 Cabo 特許經營淨產品收入與 2023 年第四季相比年增 20% 至 5.15 億美元。2024 年全年，美國 Cabo 特許經營淨產品收入與 2023 年全年相比成長 11%，達到 18.1 億美元。Exelixis 及其合作夥伴繼續保持全球領先 TKI 地位，在 2024 年第四季和全年創造的全球 cabo 特許經營淨產品收入分別約為 6.9 億美元和 25 億美元。

Chris will review our 2025 financial guidance for the base business in his prepared remarks. We will provide updated guidance, including the NET opportunity at a later date, post-approval.

克里斯將在他的準備好的演講中回顧我們針對基礎業務的 2025 年財務指導。我們將在批准後提供更新的指導，包括稍後的 NET 機會。

Second, our top priority is to advance the cabo NET indication with ongoing regulatory activities for the sNDA based on the CABINET Phase 3 pivotal trial. As you'll recall, we announced that the FDA had accepted our sNDA seeking approval for cabozantinib in both pNET or epNET indications with a PDUFA date of April 3, 2025. Detailed final results from CABINET were presented at ESMO 2024 and were concurrently published in the New England Journal of Medicine, which supported the addition of cabo to the recently updated NCCN guidelines for NET.

其次，我們的首要任務是根據 CABINET 第三階段關鍵試驗，透過持續進行 sNDA 監管活動來推進 cabo NET 適應症。您可能還記得，我們​​宣布 FDA 已接受我們的 sNDA，尋求批准卡博替尼用於治療 pNET 或 epNET 適應症，PDUFA 日期為 2025 年 4 月 3 日。CABINET 的詳細最終結果在 ESMO 2024 上公佈，並同時發表在《新英格蘭醫學雜誌》上，支持將 cabo 添加到最近更新的 NCCN NET 指南中。

We're collaborating closely with the FDA on the review and won't speak to any details of that process today. As we've highlighted at recent investor conferences and webcasts, we are launch-ready and eager to engage as soon as approval is secured.

我們正在與 FDA 密切合作進行審查，今天不會透露該過程的任何細節。正如我們在最近的投資者會議和網路廣播中所強調的那樣，我們已經做好了啟動準備，並渴望在獲得批准後立即參與。

Third, we expect zanza to take center stage in 2025 as our next oncology franchise opportunity. Important, anticipated zanza data milestones from pivotal trials include top line results from STELLAR-303 in colorectal cancer and STELLAR-304 in nonclear cell kidney cancer; and a decision to advance to the Phase 3 portion of STELLAR-305 in head and neck cancer; all projected to occur in the second half of the year pending event rates for each trial.

第三，我們預計 zanza 將在 2025 年成為我們下一個腫瘤學特許經營機會的焦點。關鍵試驗中預期的重要 zanza 數據里程碑包括 STELLAR-303 在結直腸癌中的頂線結果和 STELLAR-304 在非透明細胞腎癌中的頂線結果；並決定推進 STELLAR-305 在頭頸癌治療方面的第 3 階段研究；預計所有試驗都將在下半年進行，具體取決於每項試驗的事件發生率。

In addition, we expect to initiate the STELLAR-311 trial of zanza in NET in the first half of 2025 and anticipate Merck will initiate two RCC studies evaluating zanza plus belzutifan this year.

此外，我們預計將於 2025 年上半年啟動 zanza 在 NET 中的 STELLAR-311 試驗，並預計默克公司將在今年啟動兩項評估 zanza 和 belzutifan 的 RCC 研究。

I'll remind everybody again that Exelixis is running zanza pivotal trials against the contemporary standard of care for each trial. Regorafenib for STELLAR-303, sunitinib for STELLAR-304, and a pembrol placebo combination for STELLAR-305.

我再次提醒大家，Exelixis 正在根據每項試驗的當代護理標準進行 zanza 關鍵試驗。瑞戈非尼用於 STELLAR-303，舒尼替尼用於 STELLAR-304，派姆博爾安慰劑組合用於 STELLAR-305。

Recent speculation during ASCO-GI comparing zanza to cabo is misguided and a distraction from the focus of our zanza development activities. As highlighted on our third quarter call, our $5 billion projection for zanza in 2033 is based on success and indications, which we believe are independent from any overlap with cabo.

ASCO-GI 期間最近對 zanza 與 cabo 進行比較的猜測是錯誤的，並且分散了我們對 zanza 開發活動的注意力。正如我們在第三季電話會議上所強調的那樣，我們對 2033 年 zanza 50 億美元的預測是基於成功和跡象，我們認為這與 cabo 的任何重疊無關。

Fourth, as we highlighted recently, our Exelixis IND pipeline is full for the next several years with potentially differentiated molecules based on extensive preclinical testing. In 2025, we're looking to accelerate the Phase 1 development of XL309, as a potential therapy for tumors that have become refractory to PARP inhibitor therapy as well as in combination with PARP inhibitors to deepen and prolong responses.

第四，正如我們最近強調的那樣，未來幾年我們的 Exelixis IND 管道將會充滿基於廣泛臨床前測試的潛在差異化分子。2025 年，我們希望加速 XL309 的第 1 階段開發，作為對 PARP 抑制劑治療產生抗藥性的腫瘤的潛在療法，並與 PARP 抑制劑聯合使用以深化和延長治療反應。

Also, we're pleased with our progress of Phase 1 trials for XB010 and XL495, and see the opportunity to file up to 3 new INDs for XB628, XB064, and XB371. We expect a significant number of data presentations for these molecules at major scientific meetings throughout 2025.

此外，我們對 XB010 和 XL495 第 1 階段試驗的進展感到滿意，並看到為 XB628、XB064 和 XB371 提交最多 3 個新的 IND 的機會​​。我們預計，在 2025 年的各大科學會議上將會有大量關於這些分子的數據展示。

Business development activities continue to focus on late-stage assets in the GU/GI space. Back-end loaded, pay-for-success transactions that tuck nicely into our existing and potential future oncology franchise remain a top priority.

業務開發活動繼續集中於 GU/GI 領域的後期資產。後端加載、按成功付費交易可以很好地融入我們現有和未來潛在的腫瘤學特許經營中，仍然是我們的首要任務。

In terms of capital allocation, we're confident we have the balance sheet and the expected free cash flows to advance our pipeline priorities, access new high conviction assets, and continue to repurchase shares. So with that, please see our press release issued an hour ago for our fourth quarter and full year 2024 financial results and an extensive list of key corporate milestones achieved in the quarter.

在資本配置方面，我們相信我們擁有資產負債表和預期的自由現金流來推進我們的管道優先事項，獲得新的高信念資產，並繼續回購股票。因此，請參閱我們一小時前發布的有關我們 2024 年第四季度和全年財務業績的新聞稿以及本季度實現的一系列關鍵公司里程碑。

I'll now turn the call over to Chris.

我現在將電話轉給克里斯。

Thanks, Mike. For the fourth quarter 2024, the company reported total revenues of approximately $567 million, which included cabozantinib franchise net product revenues of $515.2 million. CABOMETYX net product revenues were $512.8 million, and included approximately $3 million in clinical trial sales, which is lower than our clinical trial sales in Q3 2024.

謝謝，麥克。2024 年第四季度，該公司報告總收入約為 5.67 億美元，其中包括卡博替尼特許經營淨產品收入 5.152 億美元。CABOMETYX 淨產品收入為 5.128 億美元，其中包括約 300 萬美元的臨床試驗銷售額，低於我們 2024 年第三季的臨床試驗銷售額。

As a continued reminder, clinical trial sales have historically been choppy between quarters, and we expect this to continue into the future. Gross to net for the cabozantinib franchise in the fourth quarter 2024 was 26.8%, which is incrementally higher than the gross to net we experienced in the quarter 2024 this increase in gross to net deductions in the fourth quarter of 2024 is primarily related to higher co-pay assistance for our commercial patients and Medicare Part D expenses.

需要持續提醒的是，臨床試驗銷售在各個季度之間一直波動很大，我們預計這種情況將持續到未來。2024 年第四季卡博替尼特許經營權的毛利與淨利之比為 26.8%，略高於我們在 2024 年季度經歷的毛利與淨利之比，2024 年第四季度毛利與淨利扣除額的增加主要與我們的商業患者的共同支付援助增加和 Medicare D 部分費用有關。

Additionally, we estimate that our gross to net for the full year 2025 will be between 29% and 30%. As previously disclosed, Exelixis has been designated as specified small manufacturer, which requires Exelixis to pay a 1% discount in 2025 on all Medicare Part D sales and is included in our gross to net estimate for the year.

此外，我們預計 2025 年全年毛利率將在 29% 至 30% 之間。如前所述，Exelixis 已被指定為指定小型製造商，這要求 Exelixis 在 2025 年對所有 Medicare Part D 銷售支付 1% 的折扣，並包含在我們當年的毛利與淨利估算中。

As we have mentioned in the past, gross to net tends to be higher in the first quarter of the year, and we project that the first quarter 2025 gross net will be similar, primarily due to higher co-pay assistance expenses for our commercial patients. Our CABOMETYX trade inventory was flat at 2.1 weeks on hand at the end of the year when compared to the third quarter 2024.

正如我們過去提到的那樣，每年第一季的毛淨額比率往往較高，我們預計 2025 年第一季的毛淨額比率將相似，這主要是由於我們的商業患者的共同支付援助費用較高。與 2024 年第三季相比，截至年底，我們的 CABOMETYX 貿易庫存持平於 2.1 週。

Total revenues also included approximately $51.5 million in collaboration revenues, which includes approximately $44 million in royalties earned from our partners Ipsen and Takeda on their sales of cabozantinib.

總收入還包括約 5,150 萬美元的合作收入，其中包括從我們的合作夥伴益普生和武田銷售卡博替尼獲得的約 4,400 萬美元的特許權使用費。

Our total operating expenses, excluding restructuring and impairment charges for the fourth quarter 2024 were approximately $403 million compared to $352 million in the third quarter 2024. The sequential increase in these operating expenses was primarily driven by higher manufacturing costs for drug development candidates, higher clinical trial and licensing costs, and by higher general and administrative costs in the fourth quarter 2024.

2024 年第四季度，我們的總營運費用（不包括重組和減損費用）約為 4.03 億美元，而 2024 年第三季為 3.52 億美元。這些營運費用的連續增加主要是由於 2024 年第四季藥物開發候選物的製造成本增加、臨床試驗和許可成本增加以及一般和行政費用增加。

Provision for income taxes for the fourth quarter of 2024 was approximately $44.9 million compared to a provision for income taxes of approximately $37 million for the third quarter of 2024.

2024 年第四季的所得稅準備金約為 4,490 萬美元，而 2024 年第三季的所得稅準備金約為 3,700 萬美元。

The company reported GAAP net income of approximately $139.9 million or $0.49 per share basic and $0.48 per share diluted for the fourth quarter of 2024. The company also reported non-GAAP net income of approximately $160.3 million or $0.56 per share basic and $0.55 per share diluted.

該公司報告稱，2024 年第四季的 GAAP 淨收入約為 1.399 億美元，即基本每股 0.49 美元，攤薄每股 0.48 美元。該公司還報告非 GAAP 淨收入約為 1.603 億美元，或基本每股 0.56 美元，稀釋每股 0.55 美元。

Non-GAAP net income excludes the impact of approximately $20 million of stock-based compensation expense net of the related income tax effect.

非公認會計準則淨收入不包括約 2,000 萬美元的股票薪資費用扣除相關所得稅的影響。

Cash and marketable securities for the year ended December 31, 2024 was approximately $1.75 billion.

截至 2024 年 12 月 31 日止年度的現金及有價證券約為 17.5 億美元。

During fiscal year 2024, we repurchased approximately $656 million of the company's shares, resulting in the retirement of approximately $26.4 million of the company's shares at an average price per share of $24.82.

在 2024 財年，我們回購了價值約 6.56 億美元的公司股票，導致以每股 24.82 美元的平均價格註銷了價值約 2,640 萬美元的公司股票。

As of the end of fiscal year 2024, we had approximately $294 million remaining under the $500 million stock repurchase plan authorized by the company's board in August 2024.

截至 2024 財年末，根據公司董事會於 2024 年 8 月批准的 5 億美元股票回購計劃，我們還剩餘約 2.94 億美元。

And finally, turning to our financial guidance for the full year 2025. We announced our 2025 financial guidance during the J.P. Morgan conference in January, which is detailed on slide 19 of our earnings presentation. As Mike mentioned, we will provide updated net product revenue guidance, including the net opportunity, at a later date, post-approval.

最後，談談我們對 2025 年全年的財務指引。我們在一月份的摩根大通會議上宣布了我們的 2025 年財務指引，詳情載於我們的財報第 19 頁。正如麥克所提到的，我們將在批准後的稍後時間提供更新的淨產品收入指導，包括淨機會。

And with that, I'll turn the call back over to Mike.

說完這些，我將把電話轉回給麥克。

All right. Thanks, Chris. I'll wrap up here by thanking the entire Exelixis team for their outstanding efforts in 2024. As I've said previously, success never comes in a straight line in this business, and I want to commend everyone at Exelixis for their individual and collective urgency and resilience as we navigated our past challenges and continue to advance our discovery, development, and commercial priorities.

好的。謝謝，克里斯。最後，我要感謝整個 Exelixis 團隊在 2024 年所做的傑出努力。正如我之前所說，在這個行業中，成功從來都不是直線而來的，我要讚揚 Exelixis 的每一位員工，感謝他們在我們克服過去的挑戰並繼續推進我們的發現、開發和商業優先事項時所表現出的個人和集體的緊迫感和韌性。

2025 is already shaping up to be another inflection year for the business, and the patients we hope to serve now and in the future. I am so proud to be part of the team that makes every hour count as we excel on our mission to help cancer patients recover stronger and live longer. We look forward to updating you on our progress in the future.

2025 年即將成為我們業務的另一個轉折年，也是我們現在和將來希望服務的患者的未來。我很自豪能夠成為團隊的一員，我們珍惜每一小時，並出色地完成我們的使命，幫助癌症患者恢復得更強，延長壽命。我們期待向您通報我們未來的進展。

Thank you for your continued support and interest in Exelixis, and we're happy to now open the call for questions.

感謝您對 Exelixis 的持續支持和關注，我們很高興現在開始回答問題。

(Operator Instructions) Asthika Goonewardene, Truist.

（操作員指示） Asthika Goonewardene，Truist。

Hi, guys. Thanks for taking my question. Congrats on all the progress made here. Mike, just for everyone who's worried about zanza looking like cabo, the misguided notion that you talked about earlier today, could you just talk to us a little bit about, one, the lack of overlap in the approved indications for cabo, and where you anticipate zanza will be?

嗨，大家好。感謝您回答我的問題。祝賀這裡取得的所有進展。麥克，對於那些擔心 zanza 看起來像 cabo 的人，以及您今天早些時候談到的錯誤觀念，您能否與我們稍微談談，第一，cabo 的獲批適應症缺乏重疊，以及您預計 zanza 會在哪裡？

And I think the important one here is, if you've ever seen the payers, I guess, force a substitution with the generic of something that is not the actual generic product. I don't think I've ever seen that happen, but I would like to get your thoughts on that.

我認為這裡重要的是，如果你曾經看過付款人強制用仿製藥取代非實際仿製藥。我認為我從未見過這種情況，但我想聽聽你對此的看法。

Yeah. Thanks, Ashtika. Look, I don't want to speculate on that level of details. I think the main focus is we are comparing zanza combinations to individual standards of care for STELLAR-303 and STELLAR-305. We certainly plan to do that with STELLAR-304 as well as what we have planned for 311 in the NET area. So the goal here is to obviously run large global randomized pivotal trials that will allow us to generate positive data if it's there to be able to push those indications forward.

是的。謝謝，Ashtika。聽著，我不想對這種程度的細節進行猜測。我認為我們主要的關注點在於將 zanza 組合與 STELLAR-303 和 STELLAR-305 的單獨護理標準進行比較。我們確實計劃對 STELLAR-304 進行這樣的嘗試，就像我們對 NET 區域 311 所做的計劃一樣。因此，這裡的目標顯然是進行大規模的全球隨機關鍵試驗，這將使我們能夠產生積極的數據，從而能夠推動這些指徵向前發展。

And that's the only comparison that comes to us. All the hand-waving between small data sets as a single arm or very small, randomized Phase 2 data sets is very, very challenging. Everybody knows that. We certainly know that, and we're focused on running, executing, and reading out these pivotal trials, because ultimately that's what will drive the label-enabling efforts that we need to get zanza moving forward into more patients in the commercial setting and really helping those patients who need better therapies.

這是我們能想到的唯一比較。將小資料集作為單臂或非常小的隨機第 2 階段資料集之間的所有手勢都非常非常具有挑戰性。大家都知道這一點。我們當然知道這一點，我們專注於運行、執行和讀出這些關鍵試驗，因為最終這將推動我們所需的標籤支援工作，以使 zanza 在商業環境中惠及更多患者，並真正幫助那些需要更好治療的患者。

Michael Schmidt, Guggenheim Securities.

古根漢證券公司的麥可‧施密特。

Thanks for taking our questions. One is on cabo for NET, sort of pending the label discussions and formalization, how are you currently thinking about the launch trajectory and expectations for uptake? Do you see any potential for an initial bolus here given that this is a sort of indolent disease?

感謝您回答我們的問題。一個是 cabo for NET，有點等待標籤討論和正式化，您目前如何考慮發布軌跡和接受預期？鑑於這是一種惰性疾病，您是否認為這裡有進行初始推注的潛力？

And then for zanza, can you just comment on the emerging safety profile now that we have more data and indications beyond RCC? And on balance, what are your current thoughts on the ability to maintain dose intensity with zanza especially when combining with checkpoint inhibitors? Thank you.

然後對於 zanza，現在我們擁有除了 RCC 之外的更多數據和指徵，您能否對新出現的安全性概況發表評論？總的來說，您目前對 zanza 維持劑量強度的能力有何看法，尤其是與檢查點抑制劑結合使用時？謝謝。

PJ, you want to take the first part?

PJ，你想學第一部分嗎？

Yes. Thanks for the question, Paul. So with regards to NET, as Mike mentioned, we are completely launch ready, and the team is, I would say, very excited and just ready to go so we can have the opportunity to help appropriate patients with neuroendocrine tumors pending an FDA approval.

是的。謝謝你的提問，保羅。因此，關於 NET，正如 Mike 所提到的，我們已經完全做好了啟動準備，我想說，團隊非常興奮，已經做好準備，這樣我們就有機會在獲得 FDA 批准後幫助合適的神經內分泌腫瘤患者。

That said, as we've said previously, we believe that the opportunity is significant. We’ve talked about the fact that in 2025, we look at the NET market and the oral shares within that market. We believe the oral market in 2025 and contemporary pricing dollars is about $1 billion, so substantial opportunity.

儘管如此，正如我們之前所說，我們相信這個機會是巨大的。我們已經討論過這樣一個事實，即在 2025 年，我們將關注 NET 市場以及該市場中的口頭份額。我們相信，2025 年的口腔市場和當代的定價美元規模約為 10 億美元，因此機會龐大。

And when we think about the CABINET study and the data set, it's a broad data set, really the only of its kind that addresses all sites of origin for NET, all the different grades of the tumor, different STR status, et cetera. So it can really be a choice for any type of NET patient pending approval.

當我們考慮 CABINET 研究和資料集時，它是一個廣泛的資料集，實際上是唯一涉及 NET 所有起源部位、所有不同等級的腫瘤、不同的 STR 狀態等的資料集。因此，對於任何類型的等待批准的 NET 患者來說，它確實可以成為一種選擇。

We've talked about before too the overlap of customers that we see. In terms of customers both that we are calling on currently for our approved on-label indications, as well as prescribers who have already written CABOMETYX is about 80%. So that's significant. So that speaks to really the ability for us to really come out of the gates fast and accelerate the launch trajectory of this.

我們之前也討論過我們看到的客戶重疊問題。就我們目前正在呼叫的核准標籤適應症的客戶以及已經開出 CABOMETYX 的處方者而言，約佔 80%。這很重要。所以這確實說明了我們有能力快速起步並加速這一發射軌跡。

And we hear from market research that physicians are excited about the data, they like the efficacy AC. They understand the safety. And when they find out, this is cabo that they're familiar with it really makes them comfortable in terms of dose reduction and managing that toxicity profile. So we're really excited and just can't wait to get out there and bring this to patients.

我們從市場調查中得知，醫生對數據感到非常興奮，他們喜歡 AC 的功效。他們懂得安全。當他們發現這是他們熟悉的 cabo 時，它確實讓他們在減少劑量和管理毒性特徵方面感到安心。因此我們真的很興奮並且迫不及待地想把它帶給病人。

The final thing I'd mention here, too, is that the oral therapies we're competing with effectively sunitinib, everolimus, and captem are all generic. So this will also give us, we believe, a substantial advantage of share of voice and other aspects of things. So we're excited for the launch.

我在這裡最後要提到的是，我們正在有效競爭的口服療法舒尼替尼、依維莫司和卡普坦都是仿製藥。因此，我們相信這也將為我們帶來話語權和其他方面的顯著優勢。因此，我們對於這款產品的發布感到非常興奮。

Sean Laaman, Morgan Stanley.

摩根士丹利的肖恩拉曼 (Sean Laaman)。

Hi, Mike, Chris, and Susan. Hope you're all well. My question relates to the balance sheet. There's really good liquidity there despite that, I think on the cash flow statement, you bought back $650 million worth of stock. I think the commentary has been that you're winding down investment in cabo and winding it up in zanza, but you're probably looking at a net neutral outcome, if I got our past discussions correct, in terms of OpEx.

嗨，麥克、克里斯和蘇珊。祝你們一切都好。我的問題與資產負債表有關。儘管如此，但那裡的流動性確實很好，我認為在現金流量表上，你回購了價值 6.5 億美元的股票。我認為評論是，你正在減少對 cabo 的投資，並結束對 zanza 的投資，但如果我理解我們過去的討論正確的話，就營運支出而言，你可能正在考慮一個淨中性結果。

Then you've talked about accelerated development of 309, potential three new INDs I think you said, Mike. But it kind of still suggests that you're going to still end up with a highly liquid and lazy balance sheet. So how do you think about that in terms of further buybacks versus potentially bolstering the pipeline with M&A?

然後您談到了 309 的加速開發，我想您說過潛在的三個新的 IND，麥克。但這仍然表明你最終會得到一個高度流動性和懶惰的資產負債表。那麼，您如何看待進一步回購與透過併購潛在地加強庫存之間的關係？

Yeah. Thanks for the question. So I'm not sure I'd characterize that much free cash flow as lazy. If so, then most other companies would want to aspire to that. So yeah, look, I think we've articulated a plan where we have built a business and run a business with a great degree of discipline, so we can move our pipeline priorities forward with cabo, with zanza, with the rest of the pipeline, the appropriate capital allocation to buyback shares when we think the price is appropriate, and then to invest in new assets when we have the conviction that they will help move the needle for patients and for our revenue goals going forward.

是的。謝謝你的提問。所以我不確定我是否會將這麼多的自由現金流描述為懶惰。如果是這樣，那麼大多數其他公司也會渴望實現這一目標。是的，看，我認為我們已經制定了一項計劃，我們已經建立了一項業務並以高度的紀律性來運營這項業務，因此我們可以推進我們的管道優先事項，包括 cabo、zanza 和管道的其餘部分，當我們認為價格合適時，進行適當的資本配置以回購股票，然後當我們確信它們將有助於推動新收入目標並實現我們未來的資產。

So we have the opportunity, and I would argue the responsibility, to manage that very carefully, those three different tacks in terms of pipeline, in terms of returning cash to shareholders, and then BD in a way that moves the business forward in the short term the long term. So I like that optionality, and I like that flexibility.

因此，我們有機會，而且我認為也有責任非常謹慎地管理這三種不同的策略，即通路方面的策略、向股東返還現金方面的策略，以及 BD 方面的策略，從而在短期和長期內推動業務向前發展。所以我喜歡這種可選性，也喜歡這種靈活性。

We’ll spend about $1 billion in R&D this year. And we think we have the opportunity to prioritize and focus based upon how the data comes in and what that tells us in terms of where to put money behind the winners and when to stop the losers. So I think we've got that well-handled, and we're looking forward to continue to move the ball down the field in a way that helps patients and builds value for our shareholders.

我們今年將在研發上投入約 10 億美元。我們認為，我們有機會根據數據的產生方式以及數據告訴我們何時應該將資金投入獲勝者以及何時應該阻止失敗者來確定優先順序和重點。所以我認為我們處理得很好，我們期待繼續以一種既能幫助患者又能為股東創造價值的方式推動事情。

David Lebowitz, Citi.

花旗銀行的 David Lebowitz。

Thank you very much for taking the question. On the recent NET data presented in ASCO-GI, could you tell us about how we should view the various subgroups relative to actually how the drug might be used in clinical practice, and what the label might ultimately look like?

非常感謝您回答這個問題。關於 ASCO-GI 中呈現的最新 NET 數據，您能否告訴我們，我們應該如何看待各個亞組相對於藥物在臨床實踐中的實際使用方式，以及標籤最終會是什麼樣子？

Hi. David, this is Amy. Thanks for the question. So we can't really speak to what the label might look like. We're in negotiations and discussions with the agency.

你好。大衛，這是艾米。謝謝你的提問。所以我們無法確切地說出標籤是什麼樣子的。我們正在與該機構進行談判和討論。

But given the population that was evaluated in CABINET, it really reflects a very broad patient population. We have pancreatic neuroendocrine tumor, GI neuroendocrine tumor, lung neuroendocrine tumor, functional/non-functional neuroendocrine tumors, and neuroendocrine tumors enrolled regardless of their somatostatin receptor expression levels, and the benefits we're seeing across all subgroups.

但考慮到 CABINET 評估的人群，它確實反映了非常廣泛的患者群體。我們招募了胰臟神經內分泌腫瘤、胃腸道神經內分泌腫瘤、肺神經內分泌腫瘤、功能性/非功能性神經內分泌腫瘤以及神經內分泌腫瘤，無論其生長抑素受體的表達水平如何，我們都看到了所有亞群的益處。

And what was shown at ASCO-GI, was that the benefit within those patients whose tumor originates from a GI origin, their benefits were consistent with the benefit overall population. So again, broad population, we think, broadly applicable.

ASCO-GI 研究表明，腫瘤源自胃腸道的患者益處與整體人群獲益一致。因此，我們認為，該標準適用於廣泛的人群和廣泛的適用範圍。

Akash Tewari, Jefferies.

傑富瑞 (Jefferies) 的 Akash Tewari。

Hi. This is Anastasia on for Akash. I just had a follow-up question on NET. Specifically, for your 2025 guidance, just wondering how much of that comes from NETs versus other indications. If you could give us a sense of what the near-term versus long-term growth might look like, that would be great. Thanks.

你好。這是 Anastasia 為 Akash 主持的節目。我剛剛對 NET 有一個後續問題。具體來說，對於您的 2025 年指導，只是想知道其中有多少來自 NET 而不是其他適應症。如果您能讓我們了解近期和長期的成長情況，那就太好了。謝謝。

Anastasia, it's Chris. As we said at J.P. Morgan and we've said today, we haven't put NET in our guidance. We'll do that at some point in the future when we understand what our final label is and also understand what the launch trajectory is post-approval.

阿納斯塔西婭，我是克里斯。正如我們摩根大通所說的話以及我們今天所說的，我們沒有將 NET 納入我們的指導範圍。當我們了解我們的最終標籤是什麼以及了解批准後的發射軌跡是什麼時，我們會在未來的某個時候這樣做。

Gregory Renza, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Gregory Renza。

Great, good afternoon, Mike and team. Congrats on the progress. Thanks for taking my question. Mike, just in relation to that pursuit of expansion, getting more out of cabo, just beyond NET, I just wanted to ask that you comment a bit on the pushes and pulls for a submission in prostate cancer and CONTACT-02.

太好了，下午好，麥克和團隊。祝賀你取得進展。感謝您回答我的問題。麥克，只是關於追求擴張，從 Cabo 獲得更多，超越 NET，我只是想請你對前列腺癌和 CONTACT-02 提交的推動和拉動發表一些評論。

If you could just speak to your confidence in that regulatory process, of course, in absence of OS, and your plan on timing and getting the ducks in a row there?

如果您可以談談您對監管流程的信心，當然，在沒有 OS 的情況下，以及您對時間表和準備工作的計劃？

Yeah. Thanks, Greg. As we talked about early in the year at PM, our only focus right now from a regulatory point of view is getting NET the goal line having that reviewed or approved. Once we get that done, we will circle back to the prostate opportunity with CONTACT-02, and at the appropriate time, give you updates on where that's going.

是的。謝謝，格雷格。正如我們今年早些時候在 PM 所討論的那樣，從監管的角度來看，我們現在唯一的關注點是讓 NET 達到目標線並得到審查或批准。一旦我們完成這項工作，我們將透過 CONTACT-02 重新回到前列腺計畫的機會，並在適當的時候向您更新專案的進度。

Eva Fortea-Verdejo, Wells Fargo.

伊娃‧福蒂亞-維德霍 (Eva Fortea-Verdejo)，富國銀行。

This is Eva on for Derek. A quick one from us. On STELLAR-303, the patient population included is both a RAS-wild-type and mutant, but in the recent STELLAR-001 readout, the patient population was just RAS-wild type. So how should we be thinking about how the differences in patient population could impact the overall survival for zanza plus atezo? Thanks.

這是 Eva，代替 Derek。我們快速說一句。在 STELLAR-303 中，包含的患者群體既是 RAS 野生型又是突變型，但在最近的 STELLAR-001 讀數中，患者群體只是 RAS 野生型。那麼我們該如何思考患者群體的差異會如何影響 zanza 和 atezo 聯合治療的整體存活率？謝謝。

Hi, Ava. This is Amy. Thanks for the question. I'm just going to step back a second to remind everybody what was the purpose of STELLAR-001, which was really to establish or evaluate whether or not there was a contribution of components when you added atezolizumab to zanzalintinib in patients with colorectal cancer.

你好，Ava。這是艾米。謝謝你的提問。我只是想稍微回顧一下，提醒大家 STELLAR-001 的目的是什麼，它的目的實際上是為了確定或評估在結直腸癌患者中，將阿替利珠單抗添加到扎林替尼中時是否有成分貢獻。

The rationale for choosing RAS-wild-type patients was because we observed higher responses in those patients. And of course, that's one metric of contribution of components. Suffice it to say that in that study, we actually saw the contribution of atezo to zanza across all three efficacy components, namely ORR, PFS, and OS.

選擇 RAS 野生型患者的原因是因為我們觀察到這些患者的反應較高。當然，這是衡量組件貢獻的指標。可以說，在研究中，我們實際上看到了 atezo 對 zanza 在所有三種療效成分（即 ORR、PFS 和 OS）中的貢獻。

And so we're encouraged by those results. As far as the read through to 303, I think we're anticipating the events, as Mike alluded to, the second half of 2025, we are encouraged by the results that we saw in STELLAR-001, and that's really about all I can say with regard to how to pull that through.

因此我們對這些結果感到鼓舞。就 303 的解讀而言，我認為我們正在期待 Mike 提到的 2025 年下半年的事件，我們對 STELLAR-001 的結果感到鼓舞，關於如何實現這一目標，我能說的就這些了。

Jason Gerberry, Bank of America Securities.

美國銀行證券公司的 Jason Gerberry。

Hey, guys. Thank you for taking questions. Mike, I just wanted to follow up on the comments earlier about the non-overlap and the $5 billion peak. I think the thing that I think investors struggle with is RCC is still a big percentage of the addressable patients in the kind of patient build. And then the comment about the nonoverlap.

嘿，大家好。感謝您回答問題。麥克，我只是想跟進一下之前關於不重疊和 50 億美元高峰的評論。我認為投資者面臨的困難在於，RCC 仍然佔據著患者群體中可尋址患者的很大一部分。然後是關於不重疊的評論。

I guess it suggests either that the novel agent RCC combination are really what drives the incremental benefit or that you won't compare against cabo, which is one of the RCC standards of care. And I imagine the answer is we can't tell you much until second half when you and Merck disclose your trial designs, but anything you can offer just to help maybe investors get around that issue or that lack of understanding?

我猜這表明要么新型藥物 RCC 組合才是真正推動增量收益的因素，要么你不會將其與 RCC 護理標準之一 cabo 進行比較。我想答案是，直到下半年您和默克公司披露試驗設計時我們才能告訴您太多信息，但是您能提供什麼幫助來幫助投資者解決這個問題或解決缺乏理解的問題嗎？

Yeah. Thanks, Jason. Look, I would just I'll just repeat in a more abbreviated fashion that I said to Ashtika, right? I think the way to look at this is looking at how we're running the pivotal trials for 303, 305, 304, 311, and the two more trials that obviously, we haven't talked about yet; there's a little bit more information to come there.

是的。謝謝，傑森。瞧，我只想以更簡潔的方式重複我對阿什蒂卡說的話，對嗎？我認為看待這個問題的方式是看看我們如何進行 303、305、304、311 等關鍵試驗，以及顯然我們還沒有討論的另外兩項試驗；那裡還會有更多資訊。

The main focus is the comparison into the standard of care that's being run in those pivotal trials. We think and just to look forward in the RCC space, that RCC will look differently in 2030 and 2031 than it does in 2024 and 2025. You have to look at what's happening and the competitive nature of that indication and that’s true for all of oncology - to look forward to planned pivotal trials that you'll actually be able to then frame what success looks like.

主要關注點是與這些關鍵試驗中執行的護理標準進行比較。我們認為，展望 RCC 領域，2030 年和 2031 年的 RCC 將與 2024 年和 2025 年有所不同。你必須專注於正在發生的事情和該適應症的競爭性質，這對所有腫瘤學來說都是如此——期待計劃中的關鍵試驗，然後你才能夠真正確定成功的模樣。

So I understand the easy part of comparing cabo to zanza, and we're certainly excited about how zanza looks with all the caveats of having a number of small single arm in some cases, small randomized studies. The bottom line is you generate good comparative data by running the right pivotal trials where you compare against standard of care, and you compare efficacy and safety. And we're doing that, we have three going with zanza right now. We'll have three more going this year. And we expect the second wave coming after that. And that's how you define really the next wave of standard of care as we did with cabo in the late teens and early 20s, as we'll do with zanza going forward.

因此，我理解將 cabo 與 zanza 進行比較的簡單部分，並且我們對 zanza 的外觀感到非常興奮，儘管在某些情況下存在許多小型單臂、小型隨機研究的所有警告。最重要的是，您可以透過執行正確的關鍵試驗來產生良好的比較數據，在試驗中您可以與護理標準進行比較，並比較功效和安全性。我們正在這樣做，目前我們有三個人與 zanza 一起。今年我們還會再舉辦三次。我們預計第二波疫情將會隨之而來。這就是真正定義下一波護理標準的方式，正如我們在十幾歲和二十多歲時對 cabo 所做的那樣，正如我們將來對 zanza 所做的那樣。

Andy Hsieh, William Blair.

安迪謝、威廉布萊爾。

Thanks for taking my question. So the ADC modality is a core corporate focus. So I'm just curious about the learnings that you can leverage from the XB002 program to XB371 to ensure it's best-in-class. And more specifically, do they share the same antibody component?

感謝您回答我的問題。因此，ADC 模式是公司的核心重點。所以我只是好奇您可以利用從 XB002 計劃到 XB371 的哪些經驗來確保它是一流的。更具體地說，它們是否具有相同的抗體成分？

Dana?

戴娜？

Yes, sure. Thanks for the question. This is Dana. Yes, so XB002 was an anti-tissue factor targeting ADC with a microtubule targeting payload. XB371 uses the same antibody with a drug antibody ratio of 8 and a topoisomerase inhibitor drug payload.

是的，當然。謝謝你的提問。這是達娜。是的，所以 XB002 是一種針對 ADC 的抗組織因子，具有微管靶向有效載荷。XB371 使用相同的抗體，藥物抗體比例為 8，並採用拓樸異構酶抑制劑藥物有效載荷。

We're excited about how that antibody differentiates from other tissue factor antibodies because of the epitope that it binds to, not causing problems with blood clotting. And we remain excited about that potential differentiation factor. Most importantly, with 371, we're very excited about how it gives us the potential opportunity to move with a biologic with an ADC into colorectal cancer.

我們很高興知道該抗體與其他組織因子抗體的差異在於它所結合的抗原決定基不會造成血液凝固問題。我們仍然對這一潛在的差異化因素感到興奮。最重要的是，有了 371，我們非常興奮，它為我們提供了將帶有 ADC 的生物製劑應用於結直腸癌的潛在機會。

As you know, Mike's talked many times in the past about how we're really focused on building a franchise in GI with STELLAR-303 with zanza and colorectal even with cabo and NETs. So this gives us another opportunity to move into this indication and create a bit of a franchise with that.

如你所知，麥克過去曾多次談到我們如何真正專注於透過 STELLAR-303、zanza 和結直腸病甚至 cabo 和 NET 在 GI 領域建立特許經營權。所以這給了我們另一個機會進入這個領域並創造一點特許經營權。

Yaron Werber, TD Cowen.

Yaron Werber，TD Cowen。

Great. I have an interrelated question, Mike, or whoever wants to take it. For RCC, I mean it sounds like the future is going to look different than now. So should we, and I know you don't want to say too much ahead of announcing the trial design, but should we assume there's going to be a zanza belzutifan triplet combo going to first line? Is that sort of how you're thinking about it maybe with IO?

偉大的。我有一個相關的問題，麥克，或任何想回答這個問題的人。對於 RCC 來說，我的意思是未來聽起來會與現在有所不同。所以我們也應該這樣做嗎？我知道你不想在宣布試驗設計之前說太多，但我們是否應該假設 zanza belzutifan 三重奏組合會成為第一線？您對 IO 的看法是否就是這樣的？

And then secondly, just for STELLAR-305, what's the go-no-go based on the Phase 2, what do you want to see then to progress into the Phase 3?

其次，僅就 STELLAR-305 而言，基於第 2 階段的可行方案是什麼，您希望看到什麼進展到第 3 階段？

Yes. So I guess I would frame your follow-up question around RCC as I think the pharmaceutical biopharma community is everybody is working to improve standard of care going forward. I think that's how we help patients, and that's obviously how we move new molecules into the system, right? That's the goal across the board. So certainly, there's nothing different about what our strategy is here with zanza, right?

是的。因此，我想我會圍繞 RCC 來提出您的後續問題，因為我認為製藥生物製藥界每個人都在努力提高未來的護理標準。我認為這就是我們幫助患者的方式，而且這顯然也是我們將新分子引入系統的方式，對嗎？這是全體人員共同的目標。所以當然，我們針對 zanza 的策略沒有什麼不同，對吧？

We're using what we think is a best-in-class TKI with the appropriate combination partners to be able to compare against contemporaneous standards of care molecules to be able to improve efficacy and safety. So it's a standard process. But looking ahead, if you assume these are going to be the same five years ahead, then, to be frank, we're all dropping the ball, right? Come on. That's the goal. The goal is to improve outcomes for patients. That's why we're here.

我們正在使用我們認為是一流的 TKI 與適當的組合夥伴，以便能夠與同期的護理分子標準進行比較，從而提高療效和安全性。所以這是一個標準流程。但展望未來，如果你認為五年後情況還會是一樣的，那麼坦白說，我們都失敗了，對嗎？快點。這就是目標。目標是改善患者的治療效果。這就是我們來這裡的原因。

So again, I don't want to get into the weeds or into the roots about what's going to happen with RCC. We will announce those trials at the appropriate time with Merck. But again, we're focused on improving standard of care for patients with cancer. We're doing it right now. The plan is with 303 in CRC, 304 in non-clear cell RCC, 305 in head and neck cancer and many more to come after that, so stay tuned.

所以再說一次，我不想深入討論 RCC 會發生什麼事。我們將與默克公司在適當的時候公佈這些試驗。但我們再次關注的是提高癌症患者的照護標準。我們現在就正在做。該計劃包括 303 個 CRC 項目、304 個非透明細胞 RCC 項目、305 個頭頸癌項目，之後還將推出更多項目，敬請關注。

Peter Lawson, Barclays.

巴克萊銀行的彼得勞森 (Peter Lawson)。

Thank you so much. Thank you for all the detail and for taking my question. I guess maybe just around CONTACT-02 if you could give us an update on where that stands? I didn't hear it mentioned today, but I know you talked about it at the beginning of the year.

太感謝了。感謝您提供詳細資訊並回答我的問題。我想也許就在 CONTACT-02 左右，您能告訴我們最新情況嗎？我今天沒有聽到有人提到這個，但我知道你在年初就談到過這個。

Yes. Thanks, Peter. I think as I mentioned to Greg, a few minutes ago, our main focus, our singular focus, right now from a regulatory point of view is on CABINET in the NET indication, getting that approved and moving that forward. Once that's secured, then we'll focus back on CONTACT-02 and CRPC, nothing more to add on that today.

是的。謝謝，彼得。我想，正如我幾分鐘前向格雷格提到的那樣，從監管的角度來看，目前我們的主要關注點、我們唯一的關注點是 NET 指示中的 CABINET，獲得批准並推動其向前發展。一旦確保安全，我們就會重新關注 CONTACT-02 和 CRPC，今天無需再補充任何內容。

Stephen Willey, Stifel.

史蒂芬威利（Stephen Willey），Stifel。

Yeah. Thanks for taking the question. Maybe just to follow up on the question of RAS-mutational status in 303. Can you just help us understand kind of what the expected distribution of wild-type versus mutant is now expected to be in the upsized version of this trial?

是的。感謝您回答這個問題。也許只是為了跟進 303 的 RAS 突變狀態的問題。您能否幫助我們了解一下在此次試驗的擴大版本中野生型與突變型的預期分佈情況？

I know the first version, I believe, specified a primary efficacy end point that was in RAS-wild-type only. I think there was an enrollment cap that you had put in place for RAS mutants. So just wondering if you can comment on whether the upsizing now changes the expected distribution here of RAS.

我知道第一個版本指定了僅適用於 RAS 野生型的主要療效終點。我認為您為 RAS 突變體設定了入學上限。所以只是想知道您是否可以評論一下現在的升級是否會改變這裡 RAS 的預期分佈。

All right. Thanks for the question, Stephen. So, you were right, we did modify the primary end point to focus more on patients without liver metastasis - which we also referred to as the non-liver met patient population. The rationale for that was because of publications demonstrating that the prognostic situation with those patients is much stronger than, say, for example, RAS or mutation or wild type, and as well, the data that we understand from others and that we have been following that IO therapy seems to do well especially in patients without liver mets, which doesn't mean that it doesn't work in patients with liver mets, it's just most of the patients have been studied without them. So we modified the study to really focus on the non-liver met versus the ITT patient population. And right now, I can't give you what the breakdown is of the RAS-mutational status to wild-type in the study, but it will be when the data comes, you'll have that answer.

好的。謝謝你的提問，史蒂芬。所以，您說得對，我們確實修改了主要終點，以便更多地關注沒有肝轉移的患者——我們也將其稱為非肝轉移患者群體。這樣做的理由是，有出版物表明這些患者的預後情況比例如 RAS 或突變或野生型要好得多，而且，我們從其他人那裡了解到的數據以及我們一直在關注的數據表明，IO 療法似乎效果很好，特別是對於沒有肝轉移的患者，這並不意味著它對有肝轉移的患者不起作用，只是大多數患者都是在沒有肝轉移的情況下進行研究的。因此，我們修改了研究內容，真正將重點放在非肝轉移患者群體與 ITT 患者群體。現在，我無法向您提供研究中 RAS 突變狀態與野生型之間的詳細情況，但當數據出來後，您就會得到答案。

Yes. And Steve, I would refer you back to the Merck LEAP-017, both presentation and paper. When they broke out the RAS-mutational status by -- at least by hazard ratio in the forest plot, the mutant RAS population actually did better than the wild-type population, okay, hazard ratio. And from that study was 0.76 for the mutants and 0.9 for the wild-type. So again, I think if people are focused on 30 patients from a combo Phase Ib or from 30 patients from a cabo IST, I mean that was interesting to us. It certainly was hypothesis generating. But I think when the -- as the non-liver met kind of story started to evolve and then LEAP-017 came out where liver mets went the right way. In fact, the rest mutants went the other way, that was very important for us to take into account. Again, that's a large, randomized globally-run pivotal trial, so it's really the gold standard from our point of view about guiding us on how to then evolve STELLAR-303.

是的。史蒂夫，我建議您看一下默克 LEAP-017，包括簡報和論文。當他們透過森林圖中的風險比來分解 RAS 突變狀態時，突變 RAS 族群實際上比野生型族群表現更好，好吧，風險比。研究顯示，突變體為 0.76，野生型為 0.9。所以，我認為，如果人們關注的是來自組合 Ib 期的 30 名患者或來自 cabo IST 的 30 名患者，那對我們來說就很有趣。這當然是假設的產生。但我認為，當非肝臟轉移的故事開始發展，然後 LEAP-017 問世時，肝臟轉移就朝著正確的方向發展。事實上，其餘的突變體則走向了另一個方向，這對我們來說非常重要。再說一遍，這是一項大規模、隨機的全球性關鍵試驗，因此從我們的角度來看，它確實是指導我們如何發展 STELLAR-303 的黃金標準。

Ash Verma, UBS.

瑞銀的 Ash Verma。

Thanks for taking my question here. So for zanza and CRC with this ASCO GI data in hand, I'm not trying to compare it to cabo, but if you look at the zanza vs. atezo efficacy, versus what we've seen with the regorafenib, would this level of efficacy still allow you to get to your peak sales guidance more broadly speaking? Thanks.

感謝您在這裡回答我的問題。因此，對於 zanza 和 CRC，根據手頭上的 ASCO GI 數據，我並不是想將其與 cabo 進行比較，但如果您看一下 zanza 與 atezo 的療效，與我們在瑞戈非尼中看到的情況相比，這種水平的療效是否仍能讓您更廣泛地達到峰值銷售指導？謝謝。

Thanks, Ash, for the question. So we're actually encouraged by the data that we saw. Again, the study design was really to demonstrate whether or not there was a contribution of components, which we clearly did demonstrate across all three efficacy endpoints. When you actually look at the outcomes of OS, say, for example, in the ITT of 11.7 months for zanza (inaudible), that actually bodes well against what one might expect or what has been published in the literature with regorafenib where the median overall survival is anywhere from 6.5 to 7.5 months. How that pulls through to 303 remains to be seen. As Mike has said, and as we have said, it requires a very large randomized Phase 3 study that can generate a p-value that gives you some sense of truth.

謝謝 Ash 提出這個問題。因此，我們看到的數據確實令我們感到鼓舞。再次強調，研究設計實際上是為了證明是否有成分貢獻，我們在所有三個功效終點都清楚證明了這一點。當您實際查看 OS 的結果時，例如，zanza 的 ITT 為 11.7 個月（聽不清楚），這實際上預示著與人們的預期或文獻中發表的瑞戈非尼的結果相反，瑞戈非尼的中位總體生存期為 6.5 至 7.5 個月。如何達到 303 仍有待觀察。正如麥克所說，也正如我們所說，這需要一項非常大規模的隨機第 3 階段研究，才能產生一個能給你一些真實感的 p 值。

And the other thing I'll point out as well in the non-liver met patient population, the median survivals ranging from 18 to 21 months also, I think, bodes well given that the ARCAD Foundation published data from their data set that includes correct and recourse in a couple of Phase 2 studies with cas and rego as the control arm and in the non-liver met patient population, the median overall survival ranges from 12.1 to 12.9 months. And we know the median overall survival from the IO combination in non-liver mets was about 20 months. So we're benchmarking well.

我還要指出的另一點是，在非肝轉移患者群體中，中位生存期為 18 至 21 個月，我認為這是個好兆頭，因為 ARCAD 基金會發布了他們的數據集數據，該數據集包括幾項 2 期研究中的正確和追索，以 cas 和 rego 作為對照組，在非肝轉移患者生存群體中，中位。我們知道，非肝轉移患者IO合併治療的中位總存活期約為20個月。因此我們的基準測試很好。

Sudan Loganathan, Stephens.

蘇丹·洛加納坦，史蒂芬斯。

Hi, good afternoon. Thanks for taking my questions. Specifically, I want to ask about the STELLAR programs 303, 304, and 305, what will be the driving force to prioritize one program over the others to bring to market first, or does the balance sheet and the R&D guidance kind of include the potential of taking all 3 indications simultaneously, submitting for regulatory approval if the data looks good, and it's undeniable that you have that strategy to submit for approval? Thanks.

嗨，下午好。感謝您回答我的問題。具體來說，我想問 STELLAR 303、304 和 305 項目，是什麼驅動力促使您優先將一個項目推向市場，或者資產負債表和研發指導是否包括同時考慮所有 3 個適應症的潛力，如果數據看起來不錯，則提交監管部門批准，並且不可否認您有提交批准的策略？謝謝。

Yeah. Thanks for the question. Yes. The only game here is a p-value. If the trials work, obviously, we would take those forward with great speed and focus. We're in the game of running pivotal trials and then moving them forward from a regulatory point of view. And that's our business.

是的。謝謝你的提問。是的。這裡唯一的遊戲是 p 值。如果試驗成功，顯然我們將會迅速且集中地推進。我們正在進行關鍵試驗，然後從監管的角度推動其向前發展。這就是我們的業務。

So we've done that numerous times with cabo, and certainly plan on doing that again here if successful. So just we're in the execution phase, but there's no games; clearly, no games for scientists and having studies work.

我們已經和 Cabo 合作過很多次了，如果成功的話，我們當然計劃在這裡再次合作。所以我們只是處於執行階段，但沒有遊戲；顯然，科學家不能玩遊戲，研究也不能起作用。

(Operator Instructions) Chris Shibutani, Goldman Sachs.

（操作員指示）高盛的 Chris Shibutani。

This is Kevin on for Chris. I just wanted to touch on the earlier stage pipeline. You mentioned that there should be a number of presentations this year. Just wanted to ask on the amount of data that we might see and the cadence of these updates. And then as you think about 3 new INDs coming in, how are you making go/no-go decisions as it relates to these programs?

這是凱文 (Kevin) 代替克里斯 (Chris)。我只是想談談早期階段的流程。您提到今年應該會有許多演講。只是想詢問我們可能會看到的數據量以及這些更新的節奏。然後，當您考慮即將有 3 個新的 IND 進入時，您如何就這些項目做出是否進行的決定？

Dana?

戴娜？

Okay. So as Mike said in his prepared remarks, we're planning for presentations at scientific meetings. We don't typically give more information than that until the abstract is published. So I would just say stay tuned on those programs. So we're excited about the data that we're planning to present to the community on those programs.

好的。正如麥克在準備好的發言中所說，我們計劃在科學會議上進行演講。在摘要發表之前，我們通常不會提供更多資訊。所以我只想說請繼續關注這些節目。因此，我們對計劃向社區展示的有關這些計劃的數據感到非常興奮。

And then regarding the early-stage pipeline, we follow what I would consider to be best practices in the industry, which is we follow a certain cadence of IND-enabling activities, including GLP toxicology. The assets pass all of the bars that are required to convince us as well as investigators that there is a good hypothesis to be tested. We then file the INDs and start the Phase 1 trials.

關於早期階段的研發管線，我們遵循我認為的行業最佳實踐，即遵循一定的 IND 支持活動節奏，包括 GLP 毒理學。這些資產通過了所有必要的測試，使我們和調查人員相信，有一個好的假設值得檢驗。然後我們提交 IND 並開始第 1 階段試驗。

So we are progressing on that track with all three of those assets, and we'll continue to make announcements as those INDs are accepted by the FDA, and we start executing those trials.

因此，我們正在利用這三項資產沿著這條軌道前進，並且我們將在這些 IND 被 FDA 接受後繼續發佈公告，並開始執行這些試驗。

Thank you. At this time, there are no further questions. And so I will turn the call over to today's host, Susan Hubbard. Ms. Hubbard?

謝謝。目前，沒有其他問題。因此，我將把電話轉給今天的主持人蘇珊·哈伯德 (Susan Hubbard)。哈伯德女士？

Thank you, Sherry, and thank you all for joining us today. We certainly welcome your follow-up calls with any additional questions you may have. Thank you.

謝謝你，雪莉，也謝謝大家今天加入我們。如果您有其他問題，我們當然歡迎您來電諮詢。謝謝。

This concludes today's program. Thank you all for participating. You may now disconnect.

今天的節目到此結束。感謝大家的參與。您現在可以斷開連線。