Exelixis Inc (EXEL) 2022 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Exelixis Fourth Quarter and Full Year 2022 Financial Results Conference Call. My name is Vaishnavi, and I'll be your operator for today. 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.

女士們先生們，美好的一天，歡迎參加 Exelixis 第四季度和 2022 年全年財務業績電話會議。我叫 Vaishnavi，今天我將擔任您的接線員。提醒一下，此通話正在錄音以供重播。我現在想把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 Susan Hubbard 女士。請繼續。

Thank you, Vaishnavi, and thank you all for joining us for the Exelixis Fourth Quarter and Full Year 2022 Financial Results Conference Call. Joining me on today's call are Mike Morrissey, our President and CEO; and Chris Senner, our Chief Financial Officer; who will review our progress for the fourth quarter and full year 2022 ended December 31, 2022.

謝謝 Vaishnavi，也感謝大家參加 Exelixis 第四季度和 2022 年全年財務業績電話會議。我們的總裁兼首席執行官 Mike Morrissey 和我一起參加今天的電話會議；和我們的首席財務官 Chris Senner；誰將審查我們截至 2022 年 12 月 31 日的第四季度和 2022 年全年的進展情況。

P.J. Haley, our Executive Vice President of Commercial; Vicki Goodman, our Chief Medical Officer; and Peter Lamb, our Chief Scientific Officer, are also on the call today and will participate in our question-and-answer 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 Vicki Goodman；我們的首席科學官彼得·蘭姆 (Peter Lamb) 今天也參加了電話會議，並將參與我們的電話問答部分。

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 results 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，我們將參考未根據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，以解釋我們使用此類非 GAAP 措施的結果以及從我們的 GAAP 結果中得出這些措施的表格。

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業績做出前瞻性陳述。這包括關於發現、產品開發、監管、商業、財務和戰略事項的可能發展的聲明。當然，實際事件或結果可能存在重大差異。

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 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.

我們建議您參考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確定了可能導致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、產品開發、業務開發和商業化活動相關的成本水平相關的風險和不確定性.

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

有了這個，我現在將把電話轉給邁克。

All right. Thank you, Susan, and thanks to everyone for joining us on the call today. Exelixis had a strong fourth quarter and full year 2022 across all components of our business. We're pleased to see continued growth of the cabozantinib franchise in the U.S. and globally in the fourth quarter and full year '22 while advancing our discovery and development priorities to build the Exelixis' product portfolio of the future.

好的。謝謝你，蘇珊，感謝大家今天加入我們的電話會議。 Exelixis 在我們業務的所有組成部分都有強勁的第四季度和 2022 年全年。我們很高興看到 cabozantinib 特許經營權在美國和全球範圍內在第四季度和 22 年全年持續增長，同時推進我們的發現和開發優先事項以構建 Exelixis 的未來產品組合。

As we had a complete corporate update a few weeks ago at the JPMorgan Healthcare Conference, Chris and I will provide a summary of top corporate and financial highlights for the fourth quarter and key 2023 priorities before moving into Q&A with the full team.

由於我們幾週前在摩根大通醫療保健會議上進行了完整的公司更新，克里斯和我將在與整個團隊進行問答之前提供第四季度主要公司和財務亮點以及 2023 年關鍵優先事項的摘要。

First, we saw a strong performance of the cabozantinib business with continued growth in demand and revenue in the U.S. CABOMETYX maintained its status as the leading TKI for RCC in both the first-line I-O TKI market and the second-line monotherapy segment. Fourth quarter cabo franchise net product revenues grew 25% year-over-year compared to fourth quarter 2021.

首先，我們看到 cabozantinib 業務表現強勁，美國的需求和收入持續增長。CABOMETYX 在一線 I-O TKI 市場和二線單藥治療領域保持了其作為 RCC 領先 TKI 的地位。與 2021 年第四季度相比，第四季度 cabo 特許經營淨產品收入同比增長 25%。

Cabo franchise net product revenues grew 30% for the full year of 2022 compared to full year 2021 and have approximately doubled since 2020. Importantly, global cabozantinib franchise net product revenues generated by Exelixis and its partners were approximately $520 million and $1.9 billion in the fourth quarter and full year 2022, respectively. Chris will review our 2023 financial guidance in his prepared remarks.

與 2021 年全年相比，2022 年全年 Cabo 特許經營淨產品收入增長了 30%，自 2020 年以來大約翻了一番。重要的是，Exelixis 及其合作夥伴產生的全球 cabozantinib 特許經營淨產品收入在第四季度分別約為 5.2 億美元和 19 億美元分別為 2022 年季度和全年。克里斯將在他準備好的評論中回顧我們的 2023 年財務指南。

Second, our top priority for 2023 is to advance the Exelixis development pipeline with new potential cabo indications, expedite zanzalintinib, development with new pivotal trials and pursuing XB002 monotherapy and combination expansion cohorts with the goal of moving this agent into full development by year-end. Our discovery organization is advancing XB01O, XB014 and XB628 in preclinical development towards potential INDs with a range of additional projects vectoring towards development candidates, for both biologics and small molecule platforms.

其次，我們 2023 年的首要任務是推進具有新的潛在 cabo 適應症的 Exelixis 開發管道，加快 zanzalintinib，通過新的關鍵試驗進行開發，並尋求 XB002 單一療法和聯合擴展隊列，目標是在年底前將該藥物推向全面開發.我們的發現組織正在推進 XB01O、XB014 和 XB628 的臨床前開發，以實現潛在的 IND，並通過一系列額外的項目引導開發候選藥物，用於生物製劑和小分子平台。

Third, business development activities will continue to be a critical focus for Exelixis throughout 2023. The 2 new option deals with Cybrexa and Sairopa are off to a great start, and we're working closely with those teams to advance their efforts to get to an option decision as quickly as possible. Our strategy to access clinical and/or near clinical stage assets that have the potential to provide differentiated benefits to patients with cancer will continue to be our primary focus in 2023.

第三，在整個 2023 年，業務發展活動將繼續成為 Exelixis 的關鍵重點。與 Cybrexa 和 Sairopa 的兩項新選擇交易有了一個良好的開端，我們正在與這些團隊密切合作，以推進他們的努力，以實現盡快做出選擇決定。我們獲取有可能為癌症患者提供差異化益處的臨床和/或接近臨床階段資產的戰略將繼續是我們在 2023 年的主要重點。

The option deal framework is a capital and resource efficient way to generate clinical group of concept data and only pay for success if that data is supportive. And finally, on January 19, the Federal District Court in Delaware issued its ruling in the first Exelixis versus MSN case, what we refer to as MSN 1. MSN's validity challenge to the cabozantinib compound patent was rejected and MSN's proposed generic product was ruled to not infringe the Exelixis N-2 polymorph patent. MSN Did not dispute the validity of the N-2 polymorph patent, so it is also -- it also remains valid and in force and no intellectual property in the Exelixis cabozantinib patent state has been invalidated. Our attention and resources have now shifted to MSN 2, which goes to trial in October, and we will continue to vigorously protect our intellectual property rights.

期權交易框架是生成臨床概念數據組的資本和資源有效方式，並且只有在該數據支持時才為成功付費。最後，在 1 月 19 日，特拉華州聯邦地方法院對第一起 Exelixis 訴 MSN 案（我們稱之為 MSN 1）作出裁決。MSN 對卡博替尼化合物專利的有效性質疑被駁回，MSN 擬議的仿製藥被裁定為不侵犯 Exelixis N-2 多晶型專利。 MSN 沒有對 N-2 多晶型專利的有效性提出異議，所以它也是——它仍然有效，並且 Exelixis cabozantinib 專利狀態下的知識產權沒有被宣告無效。我們的注意力和資源現在已經轉移到10月份開始試用的MSN 2，我們將繼續大力保護我們的知識產權。

So with that, I see our press release issued an hour ago for our fourth quarter and full year 2022 financial results and an extensive list of key corporate milestones achieved in the quarter. I'll now turn the call over to Chris.

因此，我看到我們在一小時前發布了關於我們第四季度和 2022 年全年財務業績的新聞稿，以及本季度實現的重要企業里程碑的廣泛清單。我現在將電話轉給克里斯。

Thanks, Mike. For the fourth quarter of 2022, the company reported total revenues of approximately $424 million, which included cabozantinib franchise net product revenues of $377.4 million. CABOMETYX net product revenues were $372.6 million and included approximately $7 million in clinical trial sales. Gross to net for the cabozantinib franchise in the fourth quarter '22 was 27.9%, which is higher than the gross to net we experienced in the third quarter of 2022, but overall in line with our expectations for the year. This increase in gross net deductions in the fourth quarter of 2022 primarily related to higher PHS, Medicare Part D and co-pay systems expenses.

謝謝，邁克。 2022年第四季度，公司報告的總收入約為4.24億美元，其中包括卡博替尼特許經營產品淨收入3.774億美元。 CABOMETYX 產品淨收入為3.726億美元，其中包括約700萬美元的臨床試驗銷售額。 22 年第四季度 cabozantinib 特許經營權的毛淨比為 27.9%，高於我們在 2022 年第三季度的毛淨比，但總體上符合我們今年的預期。 2022 年第四季度淨扣除總額的增加主要與 PHS、Medicare D 部分和共同支付系統費用增加有關。

Our CABOMETYX trade inventory increased by approximately 750 units when compared to the third quarter of 2022 to approximately 2.7 weeks on hand. This increase in inventory was partially related to the timing of the Christmas and New Year's holiday at the end of 2022 and the beginning of 2023. Based on what we can see in the trade, most of this inventory has been utilized in the first few weeks of January 2023.

與 2022 年第三季度相比，我們的 CABOMETYX 貿易庫存增加了約 750 個單位，庫存量約為 2.7 週。庫存的增加部分與2022年底和2023年初的聖誕節和新年假期有關。根據我們在行業中看到的情況，大部分庫存已在前幾週使用2023 年 1 月。

Total revenues also included approximately $46 million in collaboration revenues which includes approximately $34 million of royalties earned from Ipsen and Takeda on their sales of cabozantinib. And finally, clinical trial sales have historically been choppy between quarters, and we expect this to continue in future quarters. Our total operating expenses for the fourth quarter of 2022 were approximately $472 million compared to $329 million in the third quarter of 2022.

總收入還包括約 4600 萬美元的合作收入，其中包括約 3400 萬美元的 Ipsen 和 Takeda 銷售卡博替尼的特許權使用費。最後，臨床試驗銷售歷來在兩個季度之間起伏不定，我們預計這種情況將在未來幾個季度繼續。我們 2022 年第四季度的總運營費用約為 4.72 億美元，而 2022 年第三季度為 3.29 億美元。

R&D expense was the primary driver of the increase in total operating expenses, which was primarily related to higher licensing expenses for the 3 business development deals we announced during the fourth quarter, which added approximately $130 million to our R&D expenses. Benefit from income taxes for the fourth quarter of 2022 was approximately $1.3 million compared to a provision for income taxes of approximately $19 million for the third quarter of 2022.

研發費用是總運營費用增加的主要原因，這主要與我們在第四季度宣布的 3 項業務開發交易的許可費用增加有關，這使我們的研發費用增加了約 1.3 億美元。 2022 年第四季度的所得稅收益約為 130 萬美元，而 2022 年第三季度的所得稅準備金約為 1900 萬美元。

The company reported GAAP net loss of approximately $30 million or $0.09 per share, basic and diluted, for the fourth quarter of 2022. This net loss was impacted by the approximately $130 million in new business development deals we announced in the fourth quarter of 2022. The company also reported a non-GAAP net loss of approximately $10 million or $0.03 per share, basic and diluted.

該公司報告稱，2022 年第四季度的 GAAP 淨虧損約為 3000 萬美元或每股 0.09 美元，基本和攤薄後的淨虧損。這一淨虧損受到我們在 2022 年第四季度宣布的約 1.3 億美元的新業務開發交易的影響。該公司還報告了非 GAAP 淨虧損約 1000 萬美元或每股 0.03 美元，基本和稀釋。

Non-GAAP net income excludes the impact of approximately $20 million of stock-based compensation expense net of the related income tax effect. Cash and investments for the year ended December 31, 2022, was approximately $2.1 billion. This level of cash and investments supported by our ongoing cash flow from operations provides Exelixis with the flexibility to invest in internal discovery activities and also allows us to pursue external business development opportunities to expand our pipeline.

非 GAAP 淨收入不包括扣除相關所得稅影響後的約 2000 萬美元股票補償費用的影響。截至 2022 年 12 月 31 日止年度的現金和投資約為 21 億美元。我們持續的運營現金流支持的這種現金和投資水平為 Exelixis 提供了投資於內部發現活動的靈活性，也使我們能夠尋求外部業務發展機會以擴大我們的管道。

And finally, turning to our financial guidance for the full year 2023. We announced our 2023 financial guidance at the JPMorgan conference in January and is detailed on Slide 19 of our earnings presentation.

最後，轉向我們 2023 年全年的財務指導。我們在 1 月份的摩根大通會議上宣布了 2023 年的財務指導，並在我們的收益演示文稿的幻燈片 19 中進行了詳細說明。

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

有了這個，我會把電話轉回給邁克。

All right. Thanks, Chris. As you heard on the call today, the Exelixis team had a great year in 2022, and we have even greater expectations for 2023 and beyond. As we hit our stride this year, we're thrilled to have the momentum from our cabozantinib franchise performance and are completely focused on the growth drivers across all components of the business that we hope will enable Exelixis to help many more cancer patients in the future.

好的。謝謝，克里斯。正如您今天在電話會議上聽到的那樣，Exelixis 團隊在 2022 年度過了美好的一年，我們對 2023 年及以後的期望更高。今年我們取得了長足的進步，我們很高興能從我們的卡博替尼特許經營業績中獲得動力，並完全專注於業務所有組成部分的增長動力，我們希望這將使 Exelixis 能夠在未來幫助更多的癌症患者.

I'll close by thanking the entire Exelixis team for their individual and collective efforts to support our range of discovery, development and commercial activities. The team is highly motivated every day to fulfill our mission to help cancer patients recover stronger and live longer. We set our expectations high and drive for results. While we grew considerably in 2022, we remain committed to being nimble and creative and to foster a culture of collaboration and engagement. We look forward to updating you on our progress in the future. Thank you for your continued support and interest in Exelixis. And we're now happy to open the call for questions.

最後，我要感謝整個 Exelixis 團隊為支持我們的發現、開發和商業活動所做的個人和集體努力。該團隊每天都非常積極地履行我們的使命，幫助癌症患者恢復得更好，活得更久。我們設定了很高的期望並追求結果。雖然我們在 2022 年取得了長足的發展，但我們仍然致力於保持靈活和創造性，並培養協作和參與的文化。我們期待著向您通報我們未來的進展。感謝您一直以來對 Exelixis 的支持和興趣。我們現在很高興開始提問。

(Operator Instructions)

（操作員說明）

Our first question comes from Asthika Goonewardene with Truist Securities.

我們的第一個問題來自 Truist Securities 的 Asthika Goonewardene。

Apologies for the background noise. I'm crossing Street from New York City right now. Just on XL092, I just want to get a read from you as to what kind of data we can expect this year? I know previously, we've seen data at ESMO last year. Just wanted to get an idea about updates to those combination studies that we can expect.

為背景噪音道歉。我現在正從紐約市過馬路。關於 XL092，我只是想從您那裡了解一下今年我們可以期待什麼樣的數據？我以前知道，我們去年在 ESMO 看到過數據。只是想了解一下我們可以預期的那些組合研究的更新。

All right. Thanks, Asthika. No jaywalking please, okay? Vicki, do you want to take that question? .

好的。謝謝，阿斯提卡。請不要亂穿馬路，好嗎？ Vicki，你想回答這個問題嗎？ .

Sure. Happy to. Thanks, Mike, and thanks for the question. So in terms of XL092 where zanzalintinib, as it's now called, of course, we presented the first clinical data at ESMO last year, which, again, confirm the overall profile in terms of the shorter half-life compared to cabo, and we're pleased to see early evidence of activity and a tolerable safety profile.

當然。高興。謝謝，邁克，謝謝你提出這個問題。因此，就 XL092 而言，現在稱為 zanzalintinib，當然，我們去年在 ESMO 上展示了第一份臨床數據，這再次證實了與 cabo 相比半衰期更短的整體情況，我們'很高興看到活動的早期證據和可容忍的安全狀況。

We're heavily focused on execution this year in terms of the Phase IIIs that we've recently initiated and additional Phase IIIs that we plan to initiate this year as well as the expansion cohorts on our ongoing Phase I studies. And so we'll be presenting additional data as we have a meaningful data set to present, but I don't have any specific updates in terms of timing on that for you today.

根據我們最近啟動的 III 期和我們計劃今年啟動的其他 III 期以及我們正在進行的 I 期研究的擴展隊列，我們今年非常關注執行。因此，我們將提供更多數據，因為我們有一個有意義的數據集要提供，但我今天沒有任何關於時間的具體更新。

The next question comes from Michael Schmidt with Guggenheim. .

下一個問題來自古根海姆的邁克爾施密特。 .

Just 2 quick ones for me. I mean, first, on your 2023 product sales guidance, just help us understand some of the key assumptions for where the additional growth is coming from this year for CABOMETYX. And then secondly, on the CONTACT-02 study, which is the CRPC trial, help us understand your key powering assumptions for CABOMETYX as well as the control arm in the post-hormone therapy setting in prostate cancer.

對我來說只有 2 個快速的。我的意思是，首先，在您的 2023 年產品銷售指南中，只是幫助我們了解 CABOMETYX 今年額外增長來自何處的一些關鍵假設。其次，在 CRPC 試驗 CONTACT-02 研究中，幫助我們了解您對 CABOMETYX 的關鍵動力假設以及前列腺癌激素治療後設置的控制臂。

Thanks, Michael. So first question, Chris, why don't you start; P.J., you can provide some commentary on that as well; and then we'll pivot over to Vicki on second question.

謝謝，邁克爾。所以第一個問題，克里斯，你為什麼不開始？ P.J.，你也可以提供一些評論；然後我們將在第二個問題上轉向 Vicki。

Sure. Michael, it's Chris. So as you know, our guidance is $1.75 billion to $1.675 billion. That has growth in the range of 13% to 20%. And all of that growth is coming from new -- from current indications, no new indications. And we haven't assumed any comparator sales in there. And I guess P.J. can talk about the market dynamics around growth.

當然。邁克爾，是克里斯。如您所知，我們的指導價為 17.5 億美元至 16.75 億美元。增長率在 13% 到 20% 之間。所有這些增長都來自新的——來自當前的跡象，沒有新的跡象。而且我們還沒有假設那裡有任何比較器銷售。我想 P.J. 可以談談圍繞增長的市場動態。

Yes. Thanks, Chris, and thanks for the question. With regards to the business, we had a strong 2022 and finished the year not only is the #1 monotherapy TKI and RCC, but also the #1 TKI I-O combo. As we've talked about previously, we are seeing continued growth in demand driven by market share increases from increasing duration. And particularly in the last 4 months or so of the year, we saw an increase in new patient starts. So both of those together should fuel growth, we believe, in 2023. On top of that, we're certainly excited to have 44-month follow-up data from the 9ER study presented at ASCO GU and believe that will further support our positioning in the marketplace. So that's how we're thinking about growth in 2023.

是的。謝謝，克里斯，謝謝你提出這個問題。在業務方面，我們在 2022 年表現強勁，這一年不僅是排名第一的單一療法 TKI 和 RCC，還有排名第一的 TKI I-O 組合。正如我們之前談到的那樣，我們看到市場份額因持續時間增加而增加，從而推動需求持續增長。特別是在今年的最後 4 個月左右，我們看到新患者開始增加。因此，我們相信，這兩者將共同推動 2023 年的增長。最重要的是，我們當然很高興在 ASCO GU 上獲得 9ER 研究的 44 個月隨訪數據，並相信這將進一步支持我們的定位在市場上。這就是我們考慮 2023 年增長的方式。

That's great. Thanks, PJ. Vicki, you want to handle the CONTACT-02 question at high level?

那太棒了。謝謝，PJ。 Vicki，你想高級別處理 CONTACT-02 問題嗎？

Sure thing. So in terms of CONTACT-02, as you mentioned, this is our study of cabozantinib and atezolizumab in metastatic castrate-resistant prostate cancer. As we've announced, we expect to have data for the progression-free survival endpoint in the second half of this year. And in terms of the power, what I can say is it's powered for both progression-free survival as well as overall survival to demonstrate a meaningful effect in those 2 endpoints.

當然可以。因此，就 CONTACT-02 而言，正如您提到的，這是我們在轉移性去勢抵抗性前列腺癌中對 cabozantinib 和 atezolizumab 的研究。正如我們所宣布的，我們預計將在今年下半年獲得無進展生存終點的數據。就功效而言，我能說的是，它對無進展生存期和總生存期都有影響，以證明對這兩個終點具有有意義的影響。

The next question comes from Do Kim with Piper Sandler.

下一個問題來自 Do Kim 和 Piper Sandler。

This is Skyler on for Do Kim. Regarding the CONTACT-03 study, I'm wondering if you can speak to what you believe the incremental opportunity is, given cabo monotherapy is already leading second line RCC? Just where you see the upside in the market share revenues?

這是 Do Kim 的 Skyler。關於 CONTACT-03 研究，我想知道您是否可以談談您認為增加的機會是什麼，因為 Cabo 單一療法已經領先於二線 RCC？您在哪裡看到市場份額收入的上升空間？

Yes. Thanks for the questions, Skyler. This is P.J. Happy to address that. So CONTACT-03, as you mentioned, we have a strong position in the second line setting in RCC with approximately 50% market share with CABOMETYX monotherapy. But certainly, these patients -- they have metastatic disease, and they're still greatly in need of more and better options. So should CONTACT-03 be positive and atezolizumab adds to cabo in that setting. We kind of think about that opportunity in a couple of different ways.

是的。謝謝你的問題，斯凱勒。我是 P.J. 很樂意解決這個問題。所以 CONTACT-03，正如你提到的，我們在 RCC 的二線設置中處於強勢地位，CABOMETYX 單藥療法的市場份額約為 50%。但可以肯定的是，這些患者——他們患有轉移性疾病，他們仍然非常需要更多更好的選擇。所以 CONTACT-03 應該是陽性的，並且在那種情況下 atezolizumab 會增加 cabo。我們以幾種不同的方式考慮這個機會。

One is, we believe with better data we can expand that market share beyond 50% for sort of the CABOMETYX backbone in that setting. And we do believe that much of the 50% would convert from CABOMETYX monotherapy to combination therapy. So we see market share expansion. And then as you see a potential double in that setting, we would expect a longer duration of therapy there. So both expanding the cabo market and a longer duration of therapy is how we think about framing the growth from CONTACT-03.

一是，我們相信，有了更好的數據，我們可以將該環境中的某種 CABOMETYX 主幹的市場份額擴大到 50% 以上。我們確實相信，50% 的患者中有大部分將從 CABOMETYX 單一療法轉變為聯合療法。所以我們看到市場份額擴大。然後當你在那種情況下看到一個潛在的雙倍時，我們預計那裡的治療時間會更長。因此，擴大 cabo 市場和延長治療時間是我們考慮構建 CONTACT-03 增長的方式。

The next question comes from Geoffrey Weiner with Credit Suisse.

下一個問題來自瑞士信貸的 Geoffrey Weiner。

Congrats on the progress. I just have 1 here, which is I think that Ajinomoto announced a deal in January. And I think that was the most recent addition to your ever-evolving ADC tech stack. So just wondering if you can talk a little bit more about the specific technology you got access to there. and how those capabilities sit with the deals and partnerships you already have?

祝賀進步。我這裡只有一個，我認為味之素在 1 月份宣布了一項交易。我認為這是您不斷發展的 ADC 技術棧的最新補充。所以只是想知道你是否可以多談談你在那裡獲得的具體技術。這些能力如何與您已有的交易和合作夥伴關係相結合？

Yes, this is Peter. Thanks a lot for the question. You're absolutely right. That's the kind of most recent addition to our kind of suite of collaborations on the antibody drug conjugate side. I think as most people know, we're really kind of advancing our ADC pipeline, both through some internal efforts, but also through a network of collaborators.

是的，這是彼得。非常感謝你的提問。你是絕對正確的。這是我們在抗體藥物結合方面的一系列合作中的最新成員。我認為正如大多數人所知，我們確實在推進我們的 ADC 管道，既通過一些內部努力，也通過合作者網絡。

We have Invenra, who makes most of our antibodies and also a very nice bispecific-s platform. And then we have a couple of collaborations that give us access to some site-specific conjugation technology as well as a range of payloads as well Catalent and NBE. And Ajinomoto is really another access to a different site-specific conjugation technology. So we've been using it on the research side for 6, 7, 8, 9 months now. I've been very happy with the way it's performed. So we went ahead with the deal. So we're using it to make a variety of different ADCs with different payloads, but with a very controlled drug antibody ratio.

我們有 Invenra，它製造了我們大部分的抗體，也是一個非常好的雙特異性平台。然後我們進行了幾次合作，使我們能夠訪問一些特定於站點的綴合技術以及一系列有效載荷以及 Catalent 和 NBE。而 Ajinomoto 確實是另一種對不同位點特異性結合技術的訪問。所以我們已經在研究方面使用它 6、7、8、9 個月了。我對它的表現方式非常滿意。所以我們繼續進行交易。所以我們用它來製造各種不同的 ADC，具有不同的有效載荷，但藥物抗體比例非常可控。

The next question comes from Jason Gerberry with Bank of America.

下一個問題來自美國銀行的 Jason Gerberry。

Just one, in terms of the future direction of XL092, I know the message here is that we'll get future updates as STELLAR-002 data mature. I was just wondering sort of what impact ongoing cabo trials sort of dictate the future course of the program. So i.e., CONTACT-01, I assume that probably takes long off the table. I'm curious if you'd say CONTACT-02 will dictate whether or not you'd explore XL092 in the prostate setting.

就 XL092 的未來方向而言，我知道這裡的信息是，隨著 STELLAR-002 數據的成熟，我們將獲得未來的更新。我只是想知道正在進行的 Cabo 試驗會在某種程度上決定該計劃的未來進程。因此，即 CONTACT-01，我認為這可能需要很長時間才能討論。我很好奇你是否會說 CONTACT-02 會決定你是否會在前列腺環境中探索 XL092。

And then just one follow-up on CONTACT-03. The ability to expand share beyond 50% in the second-line setting. Is that just primarily patients who got a noncabo regimen in the front line, just given the protocol restrictions in that trial around having gotten cabo frontline? I just wanted to clarify that.

然後只是 CONTACT-03 的後續行動。在二線環境中將份額擴大到 50% 以上的能力。考慮到該試驗中關於獲得 Cabo 前線的方案限制，是否主要是在前線接受非 Cabo 方案的患者？我只是想澄清一下。

Yes. Jason, thanks for the questions. Vicki, you want to take that first question, and then PJ can follow up on a second.

是的。傑森，謝謝你的提問。 Vicki，你想回答第一個問題，然後 PJ 可以跟進第二個問題。

Sure. So in terms of XL092 or zanzalintinib, so as we've said before, we are looking at data that we have from the Cabo program and using it to inform zanza development. And I think a prime example of that is the first Phase III that we started last year, STELLAR-303, which is a non-MSI-high colorectal cancer, and that was based on data that was presented early last year, again demonstrating the promise of the combination of atezolizumab and cabo. And with the similar kinase profile, we started this Phase III with zanzalintinib. I think in terms of the comment about lung cancer, we're evaluating the data from CONTACT-01. I wouldn't necessarily say that lung is off the table based on that one trial. Obviously, that's a difficult patient population in which to develop drugs. And I think careful evaluation of data may lead us to consider how best to develop zanza in a lung cancer population.

當然。因此，就 XL092 或 zanzalintinib 而言，正如我們之前所說，我們正在查看我們從 Cabo 程序獲得的數據，並使用它來為 zanza 開發提供信息。我認為這方面的一個典型例子是我們去年開始的第一個 III 期 STELLAR-303，它是一種非 MSI 高結直腸癌，它基於去年初提供的數據，再次證明了atezolizumab 和 cabo 組合的承諾。憑藉類似的激酶譜，我們開始了 zanzalintinib 的 III 期臨床試驗。我認為就肺癌的評論而言，我們正在評估 CONTACT-01 的數據。根據那項試驗，我不一定會說肺不在考慮之列。顯然，這是一個難以開發藥物的患者群體。我認為仔細評估數據可能會讓我們考慮如何最好地在肺癌人群中開發 zanza。

Its P.J. Yes, with regards to your question, the assumption of expanding market share in the second line with CONTACT-03, should it be positive -- the assumption here is for patients who didn't receive cabo in some form, either a combo or monotherapy in the first-line setting, and there is still room to expand that market share up should that -- should we have a positive trial.

是 P.J. 是的，關於你的問題，假設 CONTACT-03 在第二線擴大市場份額，如果它是積極的 - 這裡的假設是針對沒有接受某種形式的 cabo 的患者，無論是組合或一線治療的單一療法，如果我們有一個積極的試驗，那麼仍有擴大市場份額的空間。

The next question comes from Andy Hsieh with William Blair.

下一個問題來自 Andy Hsieh 和 William Blair。

So for zanza, I'm just curious if you could characterize the Cmax or AUC over let's say, like a 24-hour period. And maybe comment on the tissue distribution compared to Cabo, just to help us gauge the potential for maybe like a superior efficacy profile. So that's my first question. Number two, really glad to see the start of that nonclear cell STELLAR-304 study, a very high unmet medical need. So from a modeling standpoint, could you give us a sense of what percentage of non-clear cell patients are eligible for the trial. Specifically, I understand excluding the chromophobe histology, it's really difficult to treat. And so we're curious about how that would impact the TAM.

所以對於 zanza，我很好奇你是否可以描述 Cmax 或 AUC 的特徵，比方說，比如 24 小時。並且可能評論與 Cabo 相比的組織分佈，只是為了幫助我們衡量可能像卓越療效概況的潛力。這是我的第一個問題。第二，非常高興看到非透明細胞 STELLAR-304 研究的開始，這是一個非常高的未滿足的醫療需求。所以從建模的角度來看，你能告訴我們有多少非透明細胞患者有資格參加試驗嗎？具體來說，我明白排除嫌色細胞組織學，它真的很難治療。因此，我們很好奇這將如何影響 TAM。

Peter, do you want to take the first part of the question on Zanza?

彼得，你想回答關於贊扎的問題的第一部分嗎？

Yes. Thanks for the question, Andy. So obviously, with zanza, the focus as we were developing it was on modulating the pharmacokinetic properties to take it from -- what cabozantinib has is a half-life of around 100 hours in patients, we're looking to reduce that. And as we showed in the data that came out late last year, happily zanza have half-life around 20 hours. So -- which is significantly shorter. We don't see nearly as much accumulation, but it's still consistent with once daily dosing. So that was the overall goal, initial goal, at least, which was achieved.

是的。謝謝你的問題，安迪。很明顯，對於 zanza，我們開發它的重點是調節藥代動力學特性以從中獲取它——卡博替尼在患者中的半衰期約為 100 小時，我們正在尋求減少它。正如我們在去年年底發布的數據中所顯示的那樣，令人高興的是，zanza 的半衰期約為 20 小時。所以 - 這明顯更短。我們幾乎沒有看到那麼多的積累，但它仍然與每天一次的劑量一致。所以這就是總體目標，至少是最初的目標，它已經實現了。

If you kind of dig into the data and to your question, start looking at actual drug level, Cmax, AUC, obviously, we've looked at that sort of calculating 3 fractions of drug as well. We're very confident that we're at doses that are pretty similar to the approved doses of cabozantinib. And I think that calculation is also backed up by some of the changes that we put on the poster as well with respect to various biomarkers, for example, changes of VEGF, VEGFR and AXL, which again, looked very similar to what we saw historically with cabozantinib.

如果您深入研究數據並回答您的問題，請開始查看實際藥物水平、Cmax、AUC，顯然，我們也研究了那種計算藥物的 3 個部分。我們非常有信心，我們的劑量與卡博替尼的批准劑量非常相似。我認為這種計算也得到了我們在海報上所做的一些變化以及各種生物標誌物的支持，例如 VEGF、VEGFR 和 AXL 的變化，這再次看起來與我們歷史上看到的非常相似與卡博替尼。

So at the end of the day, I think we're in a nice spot with respect to Cmax and AUC with what we expect to see from efficacy. And I think the efficacy we showed in the initial poster was certainly encouraging to us, [pretty nice waterfall puff] , but with a reduced half-life again, which we think should lead to easier AE management going forward.

所以在一天結束時，我認為我們在 Cmax 和 AUC 方面處於一個很好的位置，我們期望從療效中看到。我認為我們在最初的海報中展示的功效肯定對我們來說是鼓舞人心的，[非常好的瀑布粉撲]，但半衰期再次縮短，我們認為這應該會導致更容易的 AE 管理向前發展。

Fantastic. Vicki, do you want to take the second question?

極好的。 Vicki，你想回答第二個問題嗎？

Sure, happy to. So in terms of non-clear cell overall, about 25% of renal cell carcinoma is non-clear cell. Papillary actually makes up most of that. So it's about 15% of the overall RCC population, whereas chromophobe is only about 5%. So between papillary unclassified, you're already almost at 20%. So again, the majority of patients with non-clear cell RCC would be eligible for this trial and ultimately for treatment.

當然，很高興。所以就整體的非透明細胞而言，大約25%的腎細胞癌是非透明細胞癌。乳頭實際上佔了大部分。因此，它大約佔 RCC 總人口的 15%，而嫌色細胞僅佔 5% 左右。所以在乳頭狀未分類之間，你已經接近 20%。因此，大多數非透明細胞 RCC 患者將有資格參加該試驗並最終接受治療。

The next question comes from Etzer Darout with BMO Capital Markets.

下一個問題來自 BMO Capital Markets 的 Etzer Darout。

Just one for me for CBX12, we got some data at [travel] meeting or the initial data there. We saw some interesting signals in ovarian and breast cancers. Just wondered if we could expect a clinical update this year on that program? Or any update sort of with respect to future plans for development?

CBX12 只給我一個，我們在 [旅行] 會議上獲得了一些數據或那裡的初始數據。我們在卵巢癌和乳腺癌中看到了一些有趣的信號。只是想知道我們今年是否可以期待該計劃的臨床更新？或者關於未來發展計劃的任何更新？

Yes. Vicki, do you want to take that one?

是的。 Vicki，你要拿那個嗎？

Yes. So we're obviously also encouraged by the early data showing some early responses even while we're still in dose escalation. So following that update late last year, we'll work with the team at Cybrexa on future clinical updates. I would say that, again, we're still in dose escalation at this point and looking forward really to working with them to achieving a recommended Phase II dose and moving into the next stage of development, which would be expansion in a range of tumor types, obviously, which will be informed by some of the early data that we're seeing in dose escalation.

是的。因此，我們顯然也對顯示一些早期反應的早期數據感到鼓舞，即使我們仍處於劑量遞增階段。因此，繼去年底的更新之後，我們將與 Cybrexa 的團隊合作進行未來的臨床更新。我要說的是，此時我們仍處於劑量遞增階段，並期待與他們合作以達到推薦的 II 期劑量並進入下一階段的開發，這將擴展到一系列腫瘤顯然，我們在劑量遞增中看到的一些早期數據會告訴我們這些類型。

Next question comes from Akash Tewari with Jefferies.

下一個問題來自 Jefferies 的 Akash Tewari。

This is Ivy on for Akash. So we have two, if we may. The first is about the R&D spend. So what's roughly the breakdown of your R&D spend per program in your 2023 guidance And given some of the setbacks we've seen in the last couple of years, I guess, what programs do you feel most confident that will show a positive return on your invested capital? And also like what's your appetite to do a larger $2 billion to $4 billion M&A transaction. I guess my second question is on cabo. So just curious, do you think cabo will still be a growing product over the next 3 years on just RCC alone.

這是阿卡什的常春藤。如果可以的話，我們有兩個。首先是關於研發支出。那麼，在您的 2023 年指南中，您每個項目的研發支出大致細分是多少考慮到我們在過去幾年中看到的一些挫折，我想，您認為哪些項目最有信心會為您帶來積極的回報投資資本？並且還喜歡您進行 20 億至 40 億美元的更大併購交易的胃口。我想我的第二個問題是關於 cabo 的。所以很好奇，您認為 cabo 在未來 3 年內僅靠 RCC 是否仍將是一個不斷增長的產品。

There's a lot there. So we'll try to answer those questions one at a time. We may have to check back in with you around specific subquestions, but Chris, you take the first one?

那裡有很多。因此，我們將嘗試一次一個地回答這些問題。我們可能需要圍繞特定的子問題與您聯繫，但是克里斯，您接受第一個問題嗎？

Sure. From an R&D expense perspective, I mean, what we're seeing is we're seeing the costs related to the cabo studies coming down, and we're seeing the costs related to the zanzalintinib and the XB002 study is increasing as we look at 2023, and those will continue to grow into the future as the studies continue to enroll.

當然。從研發費用的角度來看，我的意思是，我們看到與 cabo 研究相關的成本在下降，我們看到與 zanzalintinib 和 XB002 研究相關的成本在增加2023 年，隨著研究繼續招收，這些將在未來繼續增長。

And then from a discovery perspective, we're continuing to do our discovery investments, including what's driven the big increase this year in 2022 where the BD deals, and we'll continue to look at those.

然後從發現的角度來看，我們將繼續進行我們的發現投資，包括推動 BD 交易在 2022 年大幅增長的原因，我們將繼續關注這些。

Yes. And in terms of -- I'm not going to give future guidance for the out years, obviously, leading TKI for RCC across the first line IO-TKI market as well as second line. So trials we have going between 313 and CONTACT-03, those look good. And again, we're in the data business, so good data begets the opportunity to keep growing the business. So stay tuned.

是的。就-我不會為未來幾年提供未來指導，顯然，在一線 IO-TKI 市場和二線市場上，領先的 RCC TKI。所以我們在 313 和 CONTACT-03 之間進行的試驗看起來不錯。再一次，我們從事數據業務，因此好的數據會帶來不斷發展業務的機會。敬請期待。

And I think her point of question was larger deal uptake.

而且我認為她的問題點是更大的交易吸收。

Yes. Okay. And that's -- we've been talking about that for a while, looking for the opportunity to pursue larger later-stage assets and potentially larger deals that won't qualify the size, obviously. It's all about conviction in the asset and the probability of success, our view on that and then the ability of those assets to generate differentiating data that we can then move forward into the commercial setting.

是的。好的。那就是——我們已經討論了一段時間，尋找機會追求更大的後期資產和可能不符合規模的更大交易，顯然。這一切都與對資產的信念和成功的可能性、我們對此的看法以及這些資產生成差異化數據的能力有關，我們可以將這些數據推進到商業環境中。

I think we've -- I think it's fair to say, we've proven that when we can generate differentiating clinical data, we can use that to drive the top line growth with cabo, and we're certainly proud of that and understand that we have to do it again and again and again and doing it through both internal and external sources is the plan. So stay tuned.

我認為我們 - 我認為可以公平地說，我們已經證明，當我們能夠生成差異化的臨床數據時，我們可以利用它來推動 cabo 的收入增長，我們當然為此感到自豪並理解我們必須一次又一次地通過內部和外部資源來做這件事，這就是計劃。敬請期待。

Next question comes from Yaron Werber with Cowen.

下一個問題來自 Yaron Werber 和 Cowen。

Great. I have a couple of questions on the pipeline. The first one on STELLAR-002, the LAG-3 PD-1 combo is really interesting. Is LAG-1, just give us a little bit of a sense, it's obviously approved in melanoma. What is LAG-3 with PD-1 showed in, let's say, RCC? And which other solid tumors are you interested in? And then for nonclear RCC, any sense, is cabo? What's the leading drug in that segment right now in first line? Does cabo or OPDIVO have any share? Or is it really sunitinib that's dominating that segment?

偉大的。我有幾個關於管道的問題。 STELLAR-002 上的第一個，LAG-3 PD-1 組合真的很有趣。是 LAG-1，只是給我們一點感覺，它顯然在黑色素瘤中得到了批准。比方說，RCC 中顯示的帶有 PD-1 的 LAG-3 是什麼？您還對哪些其他實體瘤感興趣？然後對於不明確的 RCC，任何意義上，是 cabo？目前該領域的一線藥物是什麼？ cabo 或 OPDIVO 有沒有份額？或者真的是舒尼替尼主導了這一領域？

All right. Great. So thanks, Yaron. Vicki, you want to take the first question, and then P.J. can address the second?

好的。偉大的。所以謝謝，亞龍。 Vicki，你想回答第一個問題，然後 P.J. 可以解決第二個問題嗎？

Yes. So as you noted, LAG-3 in combination with nivolumab is approved in melanoma. Other data, I would say, across other tumor types right now that are in the public domain are relatively sparse. But we're interested in the combination across a range of different solid tumors. So we've expanded that trial across several major tumor types now to really evaluate that combination, not only in the GU tumors, such as RCC, but in other major solid tumors, including hepatocellular carcinoma and others. So really an interesting combination that we're looking forward to what it will show us in terms of activity.

是的。因此，正如您所指出的，LAG-3 與 nivolumab 聯合治療黑色素瘤已獲批准。我想說的是，目前在公共領域的其他腫瘤類型的其他數據相對稀少。但我們對一系列不同實體瘤的組合感興趣。因此，我們現在將該試驗擴展到幾種主要腫瘤類型，以真正評估這種組合，不僅在 GU 腫瘤（如 RCC）中，而且在其他主要實體腫瘤中，包括肝細胞癌等。這真是一個有趣的組合，我們期待著它將在活動方面向我們展示什麼。

Yaron, this is P.J. With regards to the non-clear cell RCC market currently, I guess I'd characterize it as relatively similar to what you see. What we see in the overall market, including clear cell. Certainly, cabo has good utilization. There's guidelines in that market. Combos get utilization as well. But I guess how I think about it is with a Phase III, there's no randomized Phase III study in that setting. So should there be a positive Phase III study there, I think it's a significant area of unmet medical need without a high level of data available. So I think that would really provide an opportunity to drive a new standard of care in the setting for a lot of those patients.

Yaron，我是 P.J. 關於目前的非透明電池 RCC 市場，我想我會將其描述為與您所看到的相對相似。我們在整個市場上看到的，包括透明電池。當然，cabo 具有良好的利用率。那個市場有指導方針。組合也得到利用。但我想我是如何看待它的 III 期，在那種情況下沒有隨機的 III 期研究。因此，如果那裡有一項積極的 III 期研究，我認為這是一個沒有大量可用數據的未滿足醫療需求的重要領域。所以我認為這真的會提供一個機會，為很多這樣的患者在環境中推動新的護理標準。

May be if I can just throw in a quick question. On the 27.9% gross to net, can you give us any sense at all, how much of that is 340B just given how fast that program has grown over time?

也許我可以快速提出一個問題。在 27.9% 的毛淨比上，你能給我們任何意義嗎，考慮到該項目隨著時間的推移增長的速度，其中有多少是 340B？

Yes, Yaron, thanks for the question. Yes. I mean, it's continued to grow throughout 2022. I'm not going to give you a specific number. But as we look at 2023, we think gross to net is going to be in the range of 31% or so. And as we've seen in prior years, we saw that to be higher in Q1 and then -- and go down as we went through the year -- throughout the year in Q2, Q3 and Q4. But thanks for the question.

是的，Yaron，謝謝你的提問。是的。我的意思是，它在整個 2022 年都在持續增長。我不會給你一個具體的數字。但當我們展望 2023 年時，我們認為毛淨值將在 31% 左右的範圍內。正如我們在前幾年看到的那樣，我們看到第一季度更高，然後 - 並且在我們經歷這一年時下降 - 在第二季度，第三季度和第四季度全年。但是謝謝你的提問。

The next question comes from Jay Olson with Oppenheimer.

下一個問題來自 Jay Olson 和 Oppenheimer。

This is Cheng Li on the line for Jay. So maybe for cabo, I think you mentioned there's higher new patient start in second half '22. And just curious whether that is due to maybe more patients in the first-line setting and whether that will -- that trend will continue in 2023? And separately, on zanza, I think in the press release, you mentioned you expect to initiate the next wave of Phase III study. So maybe some color on the next wave of Phase III study in terms of the indication and also the combination approach we should expect.

我是程莉，為傑伊接聽電話。所以也許對於 cabo，我想你提到過在 22 年下半年有更高的新患者開始。只是好奇這是否是由於一線患者可能更多，以及這種趨勢是否會在 2023 年繼續？另外，關於 zanza，我想在新聞稿中，你提到你希望啟動下一波 III 期研究。因此，就適應症和我們應該期待的組合方法而言，下一波 III 期研究可能會有一些顏色。

Yes. Thanks for the question, P.J. can take the first question and then over to Vicki for the second one.

是的。感謝您提出問題，P.J. 可以回答第一個問題，然後交給 Vicki 回答第二個問題。

Yes. Thanks. This is P.J. So with regards to the new patient starts, I think not necessarily new patients from an epidemiological setting, increasing that in first-line RCC. I think what we're seeing there is we've taken share from competitors, particularly in the second half of the year. I think the team is executing at a high level. We have a great balance of data in terms of superior overall survival, safety, and tolerability and quality of life, and that's well received and perception of that data is strong in the marketplace.

是的。謝謝。我是 P.J. 所以關於新患者開始，我認為不一定是來自流行病學環境的新患者，增加一線 RCC 中的患者。我認為我們所看到的是我們已經從競爭對手那里奪取了份額，尤其是在今年下半年。我認為團隊的執行水平很高。我們在卓越的總體生存率、安全性、耐受性和生活質量方面取得了很好的數據平衡，並且在市場上很受歡迎並且對該數據的看法很強烈。

So additionally, as things kind of opened up after the pandemic, I think the opportunity to really interact more with healthcare professionals and educate them on the data, help drive to increase new patient starts and give us momentum in the second half of the year.

因此，此外，隨著大流行之後事情的發展，我認為有機會真正與醫療保健專業人員進行更多互動並就數據對他們進行教育，有助於推動增加新患者的開始，並在今年下半年為我們提供動力。

And with zanzalintinib. So just as a reminder, of course, we initiated our pivotal program last year with STELLAR-303 and STELLAR-304 in microsatellite non-MSI-high colorectal cancer and non-clear cell renal cell carcinoma, respectively. And as we've mentioned, we intend to initiate multiple additional pivotal trials in 2023. I'd say stay tuned there for additional details, and we'll certainly be happy to provide more color once we announce those trials.

還有贊扎林替尼。因此，提醒一下，當然，我們去年啟動了我們的關鍵計劃，分別在微衛星非 MSI 高結直腸癌和非透明細胞腎細胞癌中使用 STELLAR-303 和 STELLAR-304。正如我們所提到的，我們打算在 2023 年啟動多項額外的關鍵試驗。我想說的是，請繼續關注更多細節，一旦我們宣布這些試驗，我們當然會很樂意提供更多顏色。

The next question comes from Peter Lawson with Barclays.

下一個問題來自巴克萊銀行的彼得勞森。

Great. Just on Zanza, kind of when we should see the next data sets for the next data for STELLAR-304 and STELLAR-303 and then if there's any interim PFS reads that we should be thinking about?

偉大的。就 Zanza 而言，我們什麼時候應該看到 STELLAR-304 和 STELLAR-303 下一個數據的下一個數據集，然後是否有任何我們應該考慮的臨時 PFS 讀數？

Okay. Thanks, Peter., Vicki, do you want to answer that question again?

好的。謝謝，Peter.，Vicki，你想再次回答這個問題嗎？

Yes. So in terms of -- for STELLAR-303 and STELLAR-304 specifically, of course, these are Phase III trials that we've just initiated in the last few months or 6 months or so. So we're really focused right now on getting countries up and running, enrolling patients. In terms of timing, this will all be event-driven. And so it's too early at this stage to say when we expect those analyses, but we'll have more details forthcoming as those are available. The Phase I data, I would say, as I said earlier, when we have a meaningful data set, we will be sharing those at medical conferences.

是的。因此，就 STELLAR-303 和 STELLAR-304 而言，當然，這些是我們在過去幾個月或 6 個月左右剛剛啟動的 III 期試驗。所以我們現在真正專注於讓國家啟動和運行，招募患者。就時間而言，這都將是事件驅動的。因此，在現階段說我們預計何時進行這些分析還為時過早，但我們將在可用時提供更多詳細信息。第一階段的數據，我想說，正如我之前所說，當我們有一個有意義的數據集時，我們將在醫學會議上分享這些數據。

And then a question for Chris, I missed it. But the revenue contribution for clinical trial sales for '22 or Q4 would be great.

然後是克里斯的一個問題，我錯過了。但 22 年或第四季度臨床試驗銷售的收入貢獻將很大。

Yes. So Peter, it was about $7 million in the fourth quarter.

是的。所以彼得，第四季度約為 700 萬美元。

And you don't expect that to continue or just not include in that in your guidance?

你不希望這種情況繼續下去，或者只是不包括在你的指導中？

All I've said is we're not including that in our guidance numbers.

我所說的只是我們沒有將其包括在我們的指導數字中。

Next question comes from Silvan Tuerkcan with JMP Securities.

下一個問題來自 JMP Securities 的 Silvan Tuerkcan。

And congrats on the quarter. Just a quick question. Could you please remind me where we are with cost mix 313, so with the triplet in frontline RCC in terms of the next readout? And I saw that there may be some data at ASCO GU next week by risk score. What could we learn from that? And how could that inform your thinking about eventually getting this maybe into registration?

並祝賀本季度。只是一個簡單的問題。你能提醒我成本組合 313 的位置嗎，那麼就下一個讀數而言，前線 RCC 中的三聯體？我看到下週 ASCO GU 可能會有一些風險評分的數據。我們可以從中學到什麼？這怎麼能告訴你最終讓這個可能進入註冊的想法？

Thanks for the question. Vicki, do you want to take that?

謝謝你的問題。 Vicki，你要拿那個嗎？

Sure, happy to. So in terms of COSMIC-313, just as a reminder, we had the readout for the primary endpoint of progression-free survival last year. At that point, the overall survival data were immature. We did discuss the data with FDA and they asked to see more mature survival data before considering a filing. So we are expecting that we will have the second interim analysis of overall survival sometime later this year based on current projections. As appropriate, depending on the data, we would have a conversation again with FDA about whether or not a filing would be appropriate.

當然，很高興。因此，就 COSMIC-313 而言，作為提醒，我們去年獲得了主要終點無進展生存期的讀數。那時，總體生存數據還不成熟。我們確實與 FDA 討論了數據，他們要求在考慮提交之前查看更成熟的生存數據。因此，我們預計我們將根據目前的預測，在今年晚些時候的某個時候對總體生存期進行第二次中期分析。在適當的時候，根據數據，我們將再次與 FDA 就申請是否合適進行對話。

In terms of the ASCO GU data, they're still embargoed at this point, so I can't share any details. But yes, we do have a presentation by an IDMC risk category and really, again, just looking at the study enrolled poor and intermediate risk patients whether we see differences in the benefit and safety profile across those risk groups.

就 ASCO GU 數據而言，目前仍處於禁運狀態，因此我無法分享任何細節。但是，是的，我們確實有一個 IDMC 風險類別的演示文稿，而且真的，再一次，只是看看這項研究招募了低風險和中等風險的患者，我們是否看到這些風險組的益處和安全性存在差異。

The next question comes from Mike King with EF Hutton.

下一個問題來自 Mike King 和 EF Hutton。

I just want you to know that I'm sitting comfortably in my chair in my office's, and there's no vehicular traffic around, I'm actually quite safe right now. So I appreciate your interest. Just real quick on Zanza as well. I'm just wondering how you guys are thinking about -- do you have sort of like a menu of Phase III trials that you have conceptualized and just waiting for data to confirm those? Or do you -- is it purely going to be data-driven based on some of the Phase I and Phase II trials that you have in going right now?

我只想讓你知道，我正舒服地坐在辦公室的椅子上，周圍沒有車輛，實際上我現在很安全。所以我很感激你的興趣。 Zanza 也很快。我只是想知道你們是怎麼想的——你們有沒有類似於 III 期試驗的菜單，你們已經概念化了，只是在等待數據來確認這些？或者你 - 它是否純粹是基於你現在正在進行的一些第一階段和第二階段試驗的數據驅動？

Yes, Mike, great question. Vicki, do you want to take that one?

是的，邁克，好問題。 Vicki，你要拿那個嗎？

Yes. So first, I'm glad you're safely seated in your office. In terms of Zanza development, we're looking again at data from a number of different sources. Of course, the cabo data, again, coming back and referencing 303, our study in colorectal cancer also looking at emerging data from ongoing zanzalintinib cohorts, in particular, from STELLAR-001, but will increasingly be looking also from STELLAR-002, all of which may inform future development.

是的。首先，我很高興您能安全地坐在辦公室裡。在 Zanza 開發方面，我們正在重新審視來自多個不同來源的數據。當然，cabo 數據再次返回並參考 303，我們在結直腸癌方面的研究也在研究正在進行的 zanzalintinib 隊列中的新數據，特別是來自 STELLAR-001 的新數據，但也將越來越多地從 STELLAR-002 中尋找，所有其中可能會為未來的發展提供信息。

That said, we're also looking at the competitive landscape, areas of unmet need, really to evaluate what are the best opportunities here and really places where we can make a difference for patients. And so we're factoring all of that information in as we consider next indications for Zanza.

也就是說，我們也在關注競爭格局、未滿足需求的領域，真正評估這裡最好的機會是什麼，以及我們可以為患者帶來改變的真正地方。因此，在我們考慮 Zanza 的下一個適應症時，我們正在考慮所有這些信息。

Yes, because I would think that there's indications that, let's say, bevacizumab has or pazopanib or sunitinib where those are not indications for cabo and perhaps those are some areas where you could take the market share.

是的，因為我認為有跡象表明，比方說，貝伐珠單抗或帕唑帕尼或舒尼替尼不是 cabo 的適應症，也許這些是您可以佔據市場份額的一些領域。

Looking at lots of different possibilities. Certainly, we could think about where other TKIs have shown activity as well. I would say Cabo is a particularly good place to look because, of course, we have a similar kinase profile, but then also looking at novel combinations, right? And so I think the nivo-rela combination is a great example of that, where we see good evidence of activity, then there may be unexplored areas where we can -- where it might be make sense to develop those combinations.

看很多不同的可能性。當然，我們也可以考慮其他 TKI 在哪些方面表現出的活動。我會說 Cabo 是一個特別好的地方，因為當然，我們有相似的激酶譜，但也在尋找新的組合，對吧？因此，我認為 nivo-rela 組合就是一個很好的例子，在我們看到良好活動證據的地方，可能還有我們可以探索的未開發領域——開發這些組合可能有意義。

Right. Okay. And then just at a really high level, what would you say to investors is the most important milestone outside of, let's say, the MSN litigation. But just from the ongoing portfolio, what's the most important data point to Exelixis holders this year?

正確的。好的。然後就在一個非常高的水平上，你想對投資者說的是除了 MSN 訴訟之外最重要的里程碑。但僅從正在進行的投資組合來看，今年對 Exelixis 持有者來說最重要的數據是什麼？

Yes. So Mike, it's Mike. We talked about it in the prepared remarks, the main priority for us is to advance the non-cabo pipeline in development, both Zanza and XB002. Obviously, we've been very successful with cabo, top business and a few companies that even have only franchise molecule like cabo who want more, and there's certainly, the large unmet medical need for patients across the board, and we think both Zanza and XB002 are first step in that direction, and then we have a strong discovery and collaborative pipeline of molecules coming up as well. So our focus is building a pipeline of molecules that we can get over the goal line from a clinical and regulatory point of view and then get into HCPs and patients hands as quickly as possible.

是的。所以邁克，這是邁克。我們在準備好的評論中談到了這一點，我們的主要優先事項是推進非 Cabo 管道的開發，包括 Zanza 和 XB002。顯然，我們在 cabo、頂級企業和一些公司中非常成功，這些公司甚至只有像 cabo 這樣的特許經營分子，他們想要更多，當然，全面患者的大量醫療需求未得到滿足，我們認為 Zanza 和XB002 是朝著這個方向邁出的第一步，然後我們也將有一個強大的分子發現和協作管道。因此，我們的重點是建立一個分子管道，我們可以從臨床和監管的角度越過目標線，然後儘快進入 HCP 和患者手中。

Operator, do we have any more questions? I assume we don't. So I would say thank you very much for joining us today. And certainly, you're welcome to give [Ron] or myself a call or shoot us an email if you have any follow-up questions. Thanks again.

接線員，我們還有其他問題嗎？我想我們沒有。所以我要說非常感謝你今天加入我們。當然，如果您有任何後續問題，歡迎您給 [Ron] 或我本人打電話或給我們發電子郵件。再次感謝。

Goodbye.

再見。