Exelixis Inc (EXEL) 2023 Q3 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Exelixis Third Quarter 2023 Financial Results Conference Call. My name is Gigi, and I'll be your operator for today. As a reminder, this call is being recorded for replay purposes.

女士們、先生們，美好的一天，歡迎參加 Exelixis 2023 年第三季財務業績電話會議。我叫 Gigi，今天我將擔任您的接線生。謹此提醒，本次通話將會被錄音以供重播。

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.

現在我想將電話轉給今天的東道主，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, Gigi, and thank you all for joining us for the Exelixis Third Quarter 2023 Financial Results Conference Call. Joining me on today's call are Mike Morrissey, our President and CEO; Chris Senner, our Chief Financial Officer; P.J. Haley, our Executive Vice President of Commercial; Amy Peterson, our Chief Medical Officer; and Dana Aftab, our Chief Scientific Officer, who will review our progress for the third quarter 2023 ended September 30, 2023. Peter Lamb, our EVP of Scientific Strategy will join us for the Q&A portion of the call.

謝謝 Gigi，也謝謝大家參加 Exelixis 2023 年第三季財務業績電話會議。參加今天的電話會議的是我們的總裁兼執行長 Mike Morrissey； Chris Senner，我們的財務長； P.J. Haley，我們的商務執行副總裁； Amy Peterson，我們的首席醫療官；我們的首席科學官 Dana Aftab 將回顧我們截至 2023 年 9 月 30 日的 2023 年第三季度的進展。我們的科學策略執行副總裁 Peter Lamb 將與我們一起參加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，我們將提及並非根據公認會計原則計算的財務指標。請參閱今天發佈在我們網站上的新聞稿，以了解我們使用此類非 GAAP 衡量標準的原因以及根據我們的 GAAP 結果得出這些衡量標準的表格。

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. 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 costs associated with the discovery, product development, business development and commercialization activities.

在本演示過程中，我們將就未來事件和公司未來業績做出前瞻性陳述。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存在重大差異。我們請您參考我們不時向 SEC 提交的文件，這些文件在「風險因素」標題下指出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、業務開發和相關的成本水平相關的風險和不確定性。商業化活動。

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

然後，我會將電話轉給麥克。

All right. Thank you, Susan, and thanks to everyone for joining us on the call today. Exelixis had a strong and very active third quarter across all components of our business. We're excited to see the cabozantinib franchise continue to grow, both in size and potential scope while we advanced a range of discovery and development programs to build the Exelixis' pipeline of the future. Our singular goal is to improve the standard of care for patients with cancer. .

好的。謝謝蘇珊，也謝謝大家今天加入我們的電話會議。 Exelixis 第三季的業務各個組成部分都表現強勁且非常活躍。我們很高興看到卡博替尼特特許經營權在規模和潛在範圍上繼續增長，同時我們推進了一系列發現和開發計劃以建立 Exelixis 的未來管道。我們的唯一目標是提高癌症患者的照護標準。 。

Key highlights for the third quarter include: first, 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. Third quarter of 2023, cabo franchise net product revenues were approximately $426 million and approximately $586 million in the U.S. and globally, respectively. Chris and P. J. will update our progress in the quarter and provide additional commentary on our financial and commercial activities.

第三季的主要亮點包括：一是卡博替尼業務表現強勁，美國需求和收入持續成長。卡博替尼保持了 RCC 領先 TKI 的地位。 2023 年第三季度，Cabo 特許經營產品淨收入在美國和全球分別約為 4.26 億美元和約 5.86 億美元。 Chris 和 P.J. 將更新我們本季的進展情況，並對我們的財務和商業活動提供更多評論。

Second, EXEL's top priority in R&D is to deliver a pipeline of clinically and commercially differentiated medicines for large populations of cancer patients with high unmet medical needs. We'll highlight our integrated strategy, spanning discovery, development and commercialization activities that build on past and recent cabozantinib's at our upcoming R&D investor event on December 12 in New York City. Amy and Dana will highlight our third quarter progress at a high level today, and I'm excited to have them join me and P.J. as we dive into the details in December. Our upcoming R&D Day is the first we've had in many years, and we look forward to the opportunity to elaborate more broadly on our strategy to propel the organization forward and serve more patients with cancer, all in our continued efforts to generate sustainable long-term value for shareholders.

其次，EXEL 在研發方面的首要任務是為大量醫療需求未被滿足的癌症患者提供一系列臨床和商業差異化藥物。我們將在 12 月 12 日於紐約舉行的研發投資者活動中重點介紹我們的綜合策略，涵蓋基於過去和最近的卡博替尼的發現、開發和商業化活動。今天，艾米和達納將重點強調我們第三季度的高水平進展，我很高興他們能與我和 P.J. 一起在 12 月深入探討細節。我們即將到來的研發日是我們多年來的第一次，我們期待有機會更廣泛地闡述我們的策略，以推動組織向前發展並為更多癌症患者提供服務，所有這些都是我們不斷努力創造可持續的長期成果-股東的期限價值。

Third, business development activities remain a priority as we continue to see opportunities to access clinical assets, potential to generate differentiated clinical data in solid tumor indications. In September, Exelixis and Insilico announced an exclusive license agreement granting Exelixis global rights to develop and commercialize XL309, a potential best-in-class small molecule inhibitor of USP1, which has emerged as an important target for synthetic lethality in the context of BRCA-mutated tumors.

第三，業務開發活動仍然是優先事項，因為我們繼續看到獲得臨床資產的機會，以及在實體瘤適應症中產生差異化臨床數據的潛力。 9 月，Exelixis 和Insilico 宣布達成獨家許可協議，授予Exelixis 在全球開發和商業化XL309 的權利，XL309 是一種潛在的一流USP1 小分子抑製劑，已成為BRCA 背景下合成致死性的重要靶點。突變的腫瘤。

Fourth and finally, the second MSN trial took place last week at the U.S. District Court in Delaware. The case is now submitted, and we don't want to get ahead of the court by commenting or speculating on any components of the trial for a potential ruling, either today or in the future. We feel very confident in the case we presented last week and the overall strength of our cabozantinib patent state.

第四個也是最後一個，MSN 的第二次審判上週在特拉華州的美國地方法院進行。案件現已提交，我們不想在法庭上對審判的任何組成部分進行評論或猜測，以做出可能的裁決，無論是在今天還是將來。我們對上週提出的案例以及我們卡博替尼專利狀態的整體實力非常有信心。

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

因此，請參閱我們一小時前發布的關於第三季度財務業績的新聞稿以及本季度實現的主要企業亮點的詳細列表。我現在將把電話轉給克里斯。

Thanks, Mike. For the third quarter of 2023, the company reported total revenues of approximately $472 million, which included cabozantinib franchise net product revenues of $426.5 million. CABOMETYX net product revenues were $422.2 million and included approximately $14 million in clinical trial sales.

謝謝，麥克。 2023年第三季度，該公司報告總收入約4.72億美元，其中卡博替尼特許經營產品淨收入為4.265億美元。 CABOMETYX 產品淨收入為 4.222 億美元，其中包括約 1,400 萬美元的臨床試驗銷售額。

As a reminder, clinical trial sales have historically been choppy between quarters, and we expect this to continue in future quarters. Gross to net for the cabozantinib franchise in the third quarter of 2023 was 27.8%, which increased slightly when compared to the second quarter of 2023. Based on our gross to net in the first 9 months of 2023, we are estimating gross to net will be between 28% and 29% for the full year 2023. Our CABOMETYX trade inventory increased by approximately 400 units when compared to the second quarter of 2023. Total revenues also included approximately $45 million in collaboration revenues, including approximately $38 million of royalties earned from Ipsen and Takeda on their sales of cabozantinib in their respective territories.

提醒一下，臨床試驗銷售歷來在季度之間波動，我們預計這種情況在未來幾季將持續下去。卡博替尼特許經營權在2023 年第三季的毛淨比為27.8%，與2023 年第二季相比略有增加。根據我們2023 年前9 個月的毛淨比，我們估計毛淨比將2023 年全年的成長率將在28% 至29% 之間。與2023 年第二季相比，我們的CABOMETYX 貿易庫存增加了約400 單位。總收入還包括約4,500 萬美元的合作收入，其中包括約3800 萬美元的特許權使用費益普生 (Ipsen) 和武田 (Takeda) 在各自地區銷售卡博替尼 (cabozantinib)。

Our total operating expenses for the third quarter of 2023 were approximately $490 million compared to $392 million in the second quarter of 2023. The increase in total operating expenses sequentially was primarily driven by higher R&D expenses in the third quarter of 2023, which was primarily related to the $80 million upfront payment associated with in-licensing of XL309. Our SG&A expense declined in Q3 2023 when compared to Q2 2023. This decline was attributable to lower proxy advisory fees, partially offset by higher stock-based compensation expense.

我們 2023 年第三季的總營運費用約為 4.9 億美元，而 2023 年第二季為 3.92 億美元。總營運費用較上季增加主要是由於 2023 年第三季研發費用增加，這主要與與XL309 許可相關的8000 萬美元預付款。與 2023 年第二季相比，我們的 SG&A 費用在 2023 年第三季有所下降。這一下降是由於代理諮詢費用較低，但部分被較高的股票薪酬費用所抵消。

Provision for income taxes for the third quarter of 2023 was approximately $4.8 million, compared to a provision for income taxes of approximately $19.2 million for the second quarter of 2023. The company reported GAAP net income of approximately $1 million or $0.00 per share on a fully diluted basis for the third quarter 2023. Third quarter net income and EPS were impacted by the increase in R&D expense, primarily related to the $80 million upfront payment to Insilico. The company also reported non-GAAP net income of approximately $32 million or $0.10 per share on a fully diluted basis. Non-GAAP net income excludes the impact of approximately $31 million of stock-based compensation expense net of the related income tax effect.

2023 年第三季的所得稅撥備約為 480 萬美元，而 2023 年第二季的所得稅撥備約為 1,920 萬美元。該公司報告的 GAAP 淨利潤約為 100 萬美元，即每股 0.00 美元。 2023 年第三季的稀釋基礎。第三季淨利和每股盈餘受到研發費用增加的影響，主要與向Insilico 預付款8,000 萬美元有關。該公司還公佈了非 GAAP 淨利潤約為 3,200 萬美元，即完全稀釋後每股收益 0.10 美元。非 GAAP 淨利潤不包括約 3,100 萬美元的股票補償費用（扣除相關所得稅影響）的影響。

Cash and investments for the quarter ended September 30, 2023, was approximately $1.9 billion. This increased the level of cash investments supported our ongoing cash flow from operations provides Exelixis with the flexibility to invest in internal discovery activities to pursue external business development opportunities to expand our pipeline and allows us to return capital to our shareholders through the $550 million share repurchase program we announced in March of this year.

截至 2023 年 9 月 30 日的季度現金和投資約為 19 億美元。這增加了支持我們持續營運現金流的現金投資水平，使Exelixis 能夠靈活地投資於內部發現活動，尋求外部業務發展機會，擴大我們的產品線，並使我們能夠透過5.5 億美元的股票回購向股東返還資本我們在今年三月宣布了這項計畫。

During the third quarter of 2023, we repurchased approximately $218 million of Exelixis shares at an average price of $21.08. Since the commencement of this program for the share repurchase program, we have repurchased approximately $345 million of Exelixis shares at an average price of $20.35. We remain committed to fully executing on the $550 million share repurchase program this year.

2023 年第三季度，我們以 21.08 美元的平均價格回購了約 2.18 億美元的 Exelixis 股票。自從該股票回購計畫啟動以來，我們已以平均價格 20.35 美元回購了約 3.45 億美元的 Exelixis 股票。我們仍致力於今年全面執行 5.5 億美元的股票回購計畫。

Finally turning to our financial guidance for the full year 2023. Given where we are in the year, we are tightening our revenue guidance, and we are increasing our R&D and SG&A expense guidance. The increase in the R&D expense guidance is to reflect the Insilico deal we announced in September. Please see Slide 14 of our Q3 earnings presentation for further detail.

最後轉向我們 2023 年全年的財務指導。考慮到我們今年的情況，我們正在收緊我們的收入指導，並且我們正在提高我們的研發和銷售、一般管理費用指導。研發費用指引的增加是為了反映我們在 9 月宣布的 Insilico 交易。請參閱我們第三季收益簡報的投影片 14 以了解更多詳細資訊。

I'll now turn the call over to P.J.

我現在將電話轉給 P.J.

Thank you, Chris. The third quarter of 2023 was a strong quarter for the cabozantinib franchise. The team continues to execute at a very high level, which has resulted in CABOMETYX continuing to be the #1 prescribed TKI in RCC, and second-line HCC. Additionally, CABOMETYX in combination with nivolumab remains the #1 TKI plus immuno-oncology combination in first-line renal cell carcinoma.

謝謝你，克里斯。 2023 年第三季是卡博替尼系列的強勁季度。該團隊繼續以非常高的水平執行，這使得 CABOMETYX 繼續成為 RCC 和二線 HCC 中排名第一的處方 TKI。此外，CABOMETYX 與納武單抗聯用仍是第一線腎細胞癌中排名第一的 TKI 加免疫腫瘤學組合。

In terms of the business, CABOMETYX TRx volume grew 8% year-over-year in Q3 2023 relative to Q3 2022. Furthermore, the business remains strong, both in terms of demand and new patient starts. CABOMETYX continued to perform well in Q3 from both the marketplace and competitive perspective. CABOMETYX again led the TKI market basket and TRx share at 38%.

就業務而言，與 2022 年第三季相比，2023 年第三季 CABOMETYX TRx 銷量年增 8%。此外，無論是在需求還是新患者啟動方面，該業務仍然強勁。從市場和競爭角度來看，CABOMETYX 在第三季持續表現良好。 CABOMETYX 再次領先 TKI 市場籃子，TRx 份額達到 38%。

As we have discussed previously, the first-line RCC market is extremely competitive and Q3 was the fourth full quarter in which CABOMETYX plus nivolumab was the #1 prescribed TKI plus immuno-oncology combination in first-line RCC. Positive physician experience with CABOMETYX plus nivolumab continues to be reinforced as we highlight and promote the 44-month long-term follow-up CheckMate 9ER data with median overall survival for the CABOMETYX plus nivolumab arm, 49.5 months, representing an improvement of 14 months over the comparator arm significant with a hazard ratio of 0.70. These data fortify the leadership position that CABOMETYX has in the RCC marketplace.

正如我們之前討論的，一線 RCC 市場競爭極其激烈，第三季度是 CABOMETYX 加納武單抗成為一線 RCC 處方第一 TKI 加免疫腫瘤組合的第四個完整季度。隨著我們強調和推廣44 個月長期追蹤CheckMate 9ER 數據，CABOMETYX 加納武單抗的積極醫生體驗繼續得到加強，其中卡博替尼加納武單抗組的中位總生存期為49.5 個月，比之前改善了14 個月。比較臂顯著，風險比為 0.70。這些數據鞏固了 CABOMETYX 在 RCC 市場中的領導地位。

Looking forward, we are excited about the positive top line results for CONTACT-02 in metastatic castration-resistant prostate cancer as well as the recent data from the CABINET trial in neuroendocrine tumors. Both studies are in patient populations with significant unmet medical need and pending potential regulatory approval will provide the opportunity for continued growth for CABOMETYX in the coming years.

展望未來，我們對 CONTACT-02 在轉移性去勢抵抗性前列腺癌中取得的積極頂線結果以及神經內分泌腫瘤 CABINET 試驗的最新數據感到興奮。這兩項研究均針對醫療需求顯著未被滿足的患者群體，等待潛在的監管批准將為 CABOMETYX 在未來幾年的持續成長提供機會。

At our R&D Day in December, I look forward to further discussing these 2 potential opportunities for the cabozantinib franchise. Additionally, I'm excited to share at our event commercial perspective on our emerging pipeline assets. Our experience with cabo informs our strategy and ambition for zanzalintinib, XB002, XL309 and our pipeline as we focus on bringing drugs to market in areas that will provide significant impact to patients and value to Exelixis.

在 12 月的研發日上，我期待進一步討論卡博替尼系列的這兩個潛在機會。此外，我很高興在我們的活動中分享我們對新興管道資產的商業觀點。我們在cabo 的經驗為我們對zanzalintinib、XB002、XL309 和我們的管道的戰略和雄心壯志提供了信息，因為我們專注於將藥物推向將為患者帶來重大影響並為Exelixis 帶來價值的領域的市場。

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

說完，我會把電話轉給艾米。

Thanks, P.J. I want to first state how thrilled I am to be here at Exelixis. Our research and clinical pipeline is broad, both in terms of modality and targets representing a variety of development opportunities, which combined with our translational and clinical development capabilities provide an exciting and high potential platform for growth. and I'm looking forward to bringing into fruition and sharing progress at our upcoming R&D Day.

謝謝，P.J。首先我想表達一下來到 Exelixis 是多麼的激動。我們的研究和臨床管道廣泛，無論是在模式還是目標方面都代表著各種發展機會，這與我們的轉化和臨床開發能力相結合，提供了一個令人興奮和高潛力的成長平台。我期待在即將到來的研發日上取得成果並分享進展。

Today, I will provide a high-level update on our clinical pipeline with the intent of going into much more detail in December. Let's start with our most mature compound, cabozantinib. In late August, we announced positive top line data from not 1, but 2 Phase III studies. CONTACT-02, which evaluated cabozantinib plus atezolizumab in patients with metastatic castration-resistant prostate cancer, or mCRPC, and CABINET, which evaluated cabo in patients with pancreatic or extra-pancreatic neuroendocrine tumors.

今天，我將提供有關我們臨床管道的高級更新，旨在 12 月提供更多詳細資訊。讓我們從我們最成熟的化合物卡博替尼開始。 8 月下旬，我們宣布了不是 1 項而是 2 項 III 期研究的積極頂線數據。 CONTACT-02 評估了卡博替尼加阿替利珠單抗治療轉移性去勢抵抗性前列腺癌(mCRPC) 的療效，而CABINET 評估了卡博替尼(cabo) 治療胰腺或胰外神經內分泌腫瘤的療效。

I'll begin briefly with CONTACT-02. This is a randomized open-label study of cabozantinib plus atezolizumab versus second novel hormonal therapy, or NHT in patients with mCRPC. This study has multiple primary endpoints of both PFS and OS. PFS as determined by blinded independent central radiology review and RECIST 1.1. So for example, progression by PSA only was not considered a PFS event to best inform this endpoint. Eligibility was restricted to patients with measurable disease that is bone-only, nonmeasurable disease was not allowed.

我將從 CONTACT-02 開始簡要介紹。這是一項針對 mCRPC 患者進行卡博替尼合併阿替利珠單抗與第二種新型荷爾蒙療法 (NHT) 的隨機開放研究。這項研究有多個主要終點：PFS 和 OS。 PFS 由盲法獨立中央放射學審查和 RECIST 1.1 確定。例如，僅 PSA 進展不被視為 PFS 事件，無法最好地告知該終點。資格僅限於患有僅骨可測量疾病的患者，不允許患有不可測量疾病。

In August, we issued a press release noting a statistically significant PFS benefit in favor of cabo-atezo and the trend also favoring cabo-atezo in overall survival. No new safety signals were observed and adverse events were on par with what is expected from either cabo or atezo monotherapy. Based on feedback from the FDA, we will discuss a potential regulatory submission when the OS results are more mature.

8 月份，我們發布了一份新聞稿，指出 Cabo-atezo 在統計上具有顯著的 PFS 優勢，整體存活率也有利於 cabo-atezo 的趨勢。沒有觀察到新的安全訊號，不良事件與 cabo 或 atezo 單一療法的預期結果相同。根據 FDA 的回饋，當作業系統結果更加成熟時，我們將討論潛在的監管提交。

Also in August, we announced positive results from CABINET, a Phase III study conducted by the Alliance for Clinical Trials in Oncology. The study evaluated cabozantinib versus the placebo in 2 independently powered cohorts, 1 in previously treated patients with pancreatic neuroendocrine tumors or pNET, the other in patients with extra pancreatic neuroendocrine tumors or epNET so this is really 2 positive Phase III studies in 1. Data were recently presented at ESMO by Dr. Jennifer Chan, noting PFS hazard ratio of 0.27 and 0.45 in the pNET and epNET populations, respectively. In pNET, the median PFS for cabo was 11.4 months versus 3 months for placebo. And in epNET, the median PFS for cabo was 8.5 months versus 3.2 months for placebo. No new safety signals were identified for cabozantinib and we look forward to discussing these results with the FDA once we bring the data in-house.

同樣在 8 月，我們宣布了 CABINET 的積極結果，這是由腫瘤學臨床試驗聯盟進行的 III 期研究。該研究在2 個獨立動力隊列中評估了卡博替尼與安慰劑的比較，其中1 個在既往治療過的胰腺神經內分泌腫瘤或pNET 患者中，另一個在患有額外胰腺神經內分泌腫瘤或epNET的患者中，因此這實際上是1 項中的2 項積極的III 期研究。數據為Jennifer Chan 博士最近在ESMO 上發表了一項研究，指出pNET 和epNET 人群中的PFS 風險比分別為0.27 和0.45。在 pNET 中，cabo 的中位 PFS 為 11.4 個月，而安慰劑為 3 個月。在 epNET 中，cabo 的中位 PFS 為 8.5 個月，而安慰劑為 3.2 個月。卡博替尼沒有發現新的安全訊號，我們期待在將數據引入內部後與 FDA 討論這些結果。

I will now turn to zanzalintinib. Our STELLAR-001 and 002 Phase Ib/II trials are evaluating zanza monotherapy, zanza in combination with PD-1, PD-L1 immune checkpoint inhibition, and also triplet combinations of zanza, anti-PD-1 and CTLA-4 (inaudible) free targeted therapy. As you can see from the slide, we have multiple expansion cohorts in a variety of tumors testing these combinations.

我現在轉向贊扎林替尼。我們的STELLAR-001 和002 Ib/II 期試驗正在評估zanza 單藥療法、zanza 與PD-1、PD-L1 免疫檢查點抑制聯合療法，以及zanza、抗PD-1 和CTLA-4 的三聯療法（聽不清楚）免費標靶治療。正如您從幻燈片中看到的，我們在各種腫瘤中進行了多個擴展隊列來測試這些組合。

Data generated from these cohorts will serve to support expanded development for zanza. Indeed, we previously shared early yet promising data with the zanza monotherapy in patients with clear cell kidney cancer where compelling and durable responses are being observed in both cabo cab-naïve and cabo pretreated patients. These data have been accepted as late-breaking oral abstract for presentation by Dr. Monty Pal, on Friday, November 10 at the International Kidney Cancer Symposium taking place in Nashville.

這些隊列產生的數據將有助於支持 zanza 的擴大發展。事實上，我們先前分享了 zanza 單藥治療透明細胞腎癌患者的早期但有希望的數據，在未接受過 cabo cabo 治療和 cabo 預處理的患者中都觀察到了引人注目且持久的反應。這些數據已被接受為最新口頭摘要，由 Monty Pal 博士於 11 月 10 日星期五在納許維爾舉行的國際腎癌研討會上介紹。

Turning now to our registrational studies with zanza, enrollment continues into STELLAR-303, evaluating the combination of zanza plus atezo versus regorafenib in patients with non-MSI-high non-dMMR refractory metastatic colorectal cancer. This study was revised to evaluate outcomes first in patients, who do not have liver metastases, nonliver met or NLM followed by an evaluation in the ITT population. The sample size for both NLM and LM patients is capped to ensure adequate number of events in each of these analyses.

現在轉向我們的 zanza 註冊研究，繼續入組 STELLAR-303，評估 zanza 加 atezo 與瑞戈非尼聯合治療非 MSI 高非 dMMR 難治性轉移性大腸直腸癌患者的療效。這項研究經過修改，首先評估沒有肝轉移、非肝轉移或 NLM 的患者的結果，然後在 ITT 族群中進行評估。 NLM 和 LM 患者的樣本量都有上限，以確保每次分析中有足夠數量的事件。

STELLAR-304 is our Phase III trial, which compares the combination of zanza plus nivolumab to sunitinib in patients with previously untreated metastatic non-clear cell kidney cancer and is now enrolling in multiple countries.

STELLAR-304 是我們的 III 期試驗，該試驗比較了 zanza 加納武單抗與舒尼替尼聯合治療先前未經治療的轉移性非透明細胞腎癌患者的情況，目前正在多個國家進行招募。

And last but not least, STELLAR 305, our Phase II/III trial, which will evaluate zanza in combination with pembrolizumab versus pembrolizumab alone in patients with untreated PD-L1 positive advanced or metastatic squamous cell carcinoma of the head and neck was just posted to clinicaltrials.gov, and we are full gear into site activation mode. Given the emerging favorable activity and tolerability profile of zanza, we believe this combination of zanza plus pembro may result in improved outcome versus single-agent pembro and has the potential to offer patients a chemo-free option.

最後但並非最不重要的一點是，我們的II/III 期試驗STELLAR 305 剛剛發布，該試驗將評估zanza 聯合派姆單抗與單獨使用派姆單抗治療未經治療的PD-L1 陽性晚期或轉移性頭頸部鱗狀細胞癌患者的情況。ClinicalTrials.gov，我們已全面進入網站激活模式。鑑於 zanza 正在出現的良好活性和耐受性，我們相信 zanza 加 pembro 的這種組合可能會比單藥 pembro 改善結果，並有可能為患者提供免化療的選擇。

We're excited about the emerging data with zanza as monotherapy and in combination with ICI. This, combined with clinical data generated with cabo, provide compelling rationale to move zanza into broad development program that will address patients with unmet need. We will continue to evaluate the treatment landscape to inform the design and initiation of additional pivotal studies for zanza.

我們對 zanza 作為單一療法以及與 ICI 聯合治療的新數據感到興奮。這與 cabo 生成的臨床數據相結合，為將 zanza 納入廣泛的開發計劃提供了令人信服的理由，該計劃將解決患者未滿足的需求。我們將繼續評估治療前景，為 zanza 的其他關鍵研究的設計和啟動提供資訊。

I'll turn now to XB002, our antibody drug conjugate, which targets tissue factor and incorporates a modified auristatin as the payload. We've initiated expansion in multiple cohorts at 2 different doses, which will allow us to determine the best dose to take forward into registrational studies and combinations while also fulfilling project optimists. Combinations with nivolumab and with bevacizumab are also underway, and data here will serve to inform a broader clinical development program.

我現在談談 XB002，我們的抗體藥物偶聯物，它以組織因子為目標，並結合了改良的阿里他汀作為有效負載。我們已經開始以兩種不同劑量對多個隊列進行擴展，這將使我們能夠確定進行註冊研究和組合的最佳劑量，同時也滿足計畫樂觀主義者的需求。與納武單抗和貝伐珠單抗的組合也在進行中，此處的數據將為更廣泛的臨床開發計劃提供資訊。

Finally, I'm very excited about XL309, our recently acquired USP1 inhibitor. We anticipate full transfer of all obligations towards the end of this year and are in the process of assessing how best to aggressively and urgently advance this asset through dose escalation, both as monotherapy and in combination. We believe this to be a best-in-class molecule that has the potential to not only deepen responses with DNA damaging agents or agents that inhibit DNA damage repair like PARP inhibitors, but also to broaden the addressable population beyond those who carry a BRCA mutation.

最後，我對我們最近獲得的 USP1 抑制劑 XL309 感到非常興奮。我們預計將在今年年底完全轉移所有義務，並且正在評估如何最好地透過劑量遞增（單一療法和聯合療法）積極而緊急地推進這項資產。我們相信這是一種同類最佳的分子，不僅有可能加深DNA 損傷劑或抑制DNA 損傷修復的藥物（如PARP 抑制劑）的反應，而且還可以將可尋址人群擴大到攜帶BRCA 突變的人群之外。

In summary, we're advancing a robust pipeline of molecules while maximizing the potential benefit to patients from our flagship asset cabo in unmet need indications. I'm optimistic about what we can do for patients who, despite significant advances, still need better treatment options, and I'm very much looking forward to sharing more detailed information about our progress and the recently presented data at our R&D Day in December.

總之，我們正在推進強大的分子管道，同時最大限度地利用我們的旗艦資產 Cabo 在未滿足的需求適應症中為患者帶來潛在利益。我對我們能為患者做的事情感到樂觀，儘管取得了重大進展，但仍然需要更好的治療選擇，我非常期待在 12 月的研發日分享有關我們進展和最近提供的數據的更詳細信息。

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

然後，我會將電話轉給達納。

All right. Thanks, Amy. I just want to start off by saying how excited I am to be working with Amy as my partner in R&D. I've known her for quite some time, going back to the days when we were working with Genentech on cobimetinib, and having her here on the team now has brought a lot of energy and focus into our organization. We've been working together preparing for R&D Day next month, and I'm excited about what's in store for that event. So what you'll hear from me today will be just some brief highlights of what I'm planning to discuss in greater detail next month.

好的。謝謝，艾米。首先我想說的是，能夠與艾米作為我的研發合作夥伴一起工作，我感到非常興奮。我認識她已經有一段時間了，可以追溯到我們與基因泰克合作開發 cobimetinib 的日子，現在她加入團隊為我們的組織帶來了很多能量和關注。我們一直在共同努力準備下個月的研發日，我對這次活動即將發生的事情感到很興奮。因此，您今天從我這裡聽到的只是我計劃下個月更詳細討論的一些簡短要點。

In the third quarter, we made solid progress toward our goals of advancing existing development candidates toward IND filings, and advancing early discovery programs to development candidate status. We are on track to file 4 new INDs next year, 3 of which will be from existing pre-IND biotherapeutics programs and 1 of which will be for XL495, a new small molecule development candidate that we recently added to our pipeline.

在第三季度，我們在推進現有開發候選藥物向 IND 申請以及將早期發現項目推進到開發候選藥物狀態的目標方面取得了堅實進展。我們預計明年將提交4 個新的IND，其中3 個將來自現有的IND 前生物治療項目，其中1 個將針對XL495，XL495 是我們最近添加到管道中的一種新的小分子開發候選藥物。

For our existing preclinical biotherapeutics programs, we are on track with IND-enabling activities and expect to file INDs for 3 programs next year. The first will be for XB010, our 5T4 targeted antibody drug conjugate that carries the cytotoxic anti-tubulin payload, which we expect to file around mid-2024. The second IND will be for XB628, our bispecific antibody that targets PD-L1 along with NKG2A, which is on track for IND filing in the second half of 2024. And the third IND will be for XB371, a tissue factor targeting antibody drug conjugate that carries the topoisomerase 1 inhibitor payload. This program is on track for IND filing in late 2024.

對於我們現有的臨床前生物治療項目，我們正在進行 IND 支持活動，並預計明年為 3 個項目提交 IND。第一個是 XB010，這是我們的 5T4 標靶抗體藥物偶聯物，它攜帶細胞毒性抗微管蛋白有效負載，我們預計將於 2024 年中期左右提交申請。第二項IND 將針對XB628，這是我們針對PD-L1 和NKG2A 的雙特異性抗體，預計將於2024 年下半年提交IND 申請。第三項IND 將針對XB371，一種組織因子靶向抗體藥物偶聯物攜帶拓樸異構酶 1 抑制劑有效負載。該計畫預計於 2024 年底提交 IND 申請。

So as I mentioned earlier, we recently added XL495 to our pipeline. XL495 is a potent and selective small molecule inhibitor of PKMYT1 that was generated from an internal discovery program. Inhibition of PKMYT1 is synthetically lethal in the context of increased Cyclin E levels, which occurs across a wide range of tumors, including, ovarian, endometrial and colorectal. Our molecule was designed to be best-in-class and is tracking towards IND filing around mid-2024.

正如我之前提到的，我們最近將 XL495 添加到我們的管道中。 XL495 是一種有效的選擇性 PKMYT1 小分子抑制劑，由內部發現計劃產生。在 Cyclin E 水平升高的情況下，抑制 PKMYT1 具有綜合致死性，這種情況發生在多種腫瘤中，包括卵巢癌、子宮內膜癌和大腸癌。我們的分子被設計為同類最佳，並預計在 2024 年中期左右提交 IND 申請。

In addition to these programs, we expect to nominate several more development candidates from our biotherapeutics discovery programs by the end of this year. We are currently on track to reach our stated goal of up to 5 new development candidates this year, which, in addition to XL495 will include a monoclonal antibody targeting a novel immune checkpoint pathway and some new antibody drug conjugates. All of these programs represent first or best-in-class approaches and have the potential to meaningfully contribute to our mission of helping cancer patients recover stronger and live longer.

除了這些項目之外，我們預計在今年年底前從我們的生物治療發現計畫中提名更多的開發候選人。目前，我們預計將實現今年多達 5 個新開發候選藥物的既定目標，其中除了 XL495 之外，還將包括針對新型免疫檢查點途徑的單株抗體和一些新的抗體藥物偶聯物。所有這些項目都代表了首創或同類最佳的方法，並且有可能為我們幫助癌症患者康復更強、壽命更長的使命做出有意義的貢獻。

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

然後，我會將電話轉回給麥克。

All right. Thanks, Dana. As you've heard on the call today, Exelixis has had a strong third quarter of 2023 and is moving quickly to capitalize on our momentum in the fourth quarter. We're excited to advance all our efforts to help many more cancer patients as we discover and develop our pipeline of the future. We look forward to sharing our latest strategies and science at our R&D Day in December.

好的。謝謝，達納。正如您在今天的電話會議上聽到的那樣，Exelixis 在 2023 年第三季度表現強勁，並且正在迅速採取行動，以利用我們在第四季度的勢頭。當我們發現和開發未來的產品線時，我們很高興能夠盡一切努力幫助更多的癌症患者。我們期待在 12 月的研發日分享我們的最新策略和科學成果。

I'll close by thanking the entire Exelixis team for their collective efforts to support our discovery development and commercial activities. The team is highly motivated to achieve our mission to help cancer patients recover stronger and live longer. We drive our results every single day with a clear urgency and focus to build on our long history of innovation and collaboration. We look forward to updating you on our progress in the future.

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集體努力。團隊非常積極地實現我們的使命，幫助癌症患者康復得更強、壽命更長。我們每天都以明確的緊迫感推動我們的成果，並專注於鞏固我們悠久的創新和合作歷史。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 的持續支持和興趣，我們很高興現在開始提問。

(Operator Instructions) Your first question comes from the line of Michael Schmidt from Guggenheim Securities.

（操作員說明）您的第一個問題來自古根漢證券公司的邁克爾·施密特（Michael Schmidt）。

Congrats on all the progress. I just had a pipeline question regarding the upcoming STELLAR-001 zanza data at the kidney conference next week. Could you just help set some expectations here in terms of number of patients? And how many of them will be cabo-naive. How should we interpret the data coming out of the meeting?

祝賀所有的進展。我剛剛對下週腎臟會議上即將發布的 STELLAR-001 zanza 數據有一個管道問題。您能否幫忙設定一些患者數量方面的預期？他們中有多少人是天真無知的。我們該如何解讀會議所得的數據？

And then secondly, you mentioned the upcoming R&D Day a few times, could you just help us again understand sort of what to expect there? In particular, will you disclose any clinical data from some of the new or clinical stage pipeline products?

其次，您多次提到即將到來的研發日，您能否幫助我們再次了解那裡會發生什麼事？特別是，您會透露一些新的或臨床階段的管道產品的任何臨床數據嗎？

So Amy, take the first one, and we can all reply on the second one. So go ahead.

所以艾米，拿第一個，我們都可以回覆第二個。所以請繼續。

Yes. Thanks, Michael, for the question. I think we're really excited about the data that continues to emerge from zanza, especially in the clear cell kidney cancer cohort. There's not much I can give you in the terms of details simply, because the data is embargoed and the presentation is just around the corner on November 10. It will be data that is updated around the 32 patients that we've discussed before that received monotherapy with zanza. So I'm looking forward to going deeper with you on that at R&D Day, but that's about all I can say right now.

是的。謝謝邁克爾提出這個問題。我認為我們對 zanza 不斷出現的數據感到非常興奮，特別是在透明細胞腎癌隊列中。我無法簡單地向您提供太多詳細信息，因為數據已被禁止，並且演示即將在 11 月 10 日進行。這將是圍繞我們之前討論過的 32 名患者更新的數據zanza 單一療法。因此，我期待在研發日與您深入探討這個問題，但這就是我現在能說的全部。

Okay. On the R&D Day side, just again, manage expectations, as we talked about, I think, numerous times today, we're going to focus on strategy and science as the main update for investors. I wouldn't expect any new late-breaking unpublished data, and we have a commitment to our investigators to do that first. So you'll see that throughout 2024 for the new compounds. We're super excited to frame our strategy and our tactics in the context of the success we've had with cabo and how we're moving forward with the pipeline. So it will be an action-packed day, and we're looking forward to seeing you and everybody there.

好的。在研發日方面，再次管理預期，正如我們今天多次討論的那樣，我們將把重點放在策略和科學上，作為投資者的主要更新。我不希望有任何新的最新未發表的數據，我們向我們的調查人員承諾首先這樣做。因此，您將在 2024 年看到新化合物的情況。我們非常高興能夠在 Cabo 取得的成功以及我們如何推進管道的背景下制定我們的策略和戰術。因此，這將是充滿活力的一天，我們期待與您和所有人見面。

Our next question comes from the line of Jason Gerberry from Bank of America.

我們的下一個問題來自美國銀行的 Jason Gerberry。

Mike, I know you can't talk a lot about the IP with cabo, but my question is more -- is there any engagement with MSN as a counterparty regarding settlement? Or do you feel you're operating with a counterparty unwilling to engage in settlement talks? We know that settlements do occur post trial in some instances as well. So just curious to the extent you can comment on that dynamic. I appreciate it.

Mike，我知道您不能與 cabo 談論太多有關 IP 的問題，但我的問題更多 - 是否與 MSN 作為交易對手方就和解事宜進行過接觸？或者您認為您正在與不願意參與和解談判​​的交易對手進行交易？我們知道，在某些情況下，審判後也會達成和解。所以只是好奇你能對這種動態發表評論。我很感激。

Yes, Jason, thanks for the question. Again, I really can't say a lot here. We're -- I'll put it this way. We like talking to people. We have a variety of different collaborators, who we work very closely with. It's in our culture, it's in our DNA to be as open and interactive as possible. So that goes here, right? If there's a settlement to be had, we won't be rate limiting in how we view that.

是的，傑森，謝謝你的提問。再說一遍，我真的不能在這裡說太多。我們──我會這樣說。我們喜歡與人交談。我們有各種各樣的合作者，我們與他們密切合作。盡可能開放和互動是我們的文化和 DNA 的一部分。那就到這裡吧？如果能夠達成和解，我們不會限制我們的看法。

Again, I think we had a really strong week last week. I'm not going to get ahead of the court. They have their job to do. I was super -- and I think the whole team was just super proud about being able to go out there and put the context of the trial, the data, the legalities into context, and it's now in the hands of the court. But you're right, things can happen when they happen. And if there's a settlement opportunity, we'll certainly engage them.

再說一次，我認為上週我們度過了非常強烈的一周。我不會在法庭上領先。他們有自己的工作要做。我太棒了——我認為整個團隊都非常自豪能夠走出去，將審判的背景、數據、合法性融入背景中，而現在一切都掌握在法庭手中。但你是對的，事情發生時就會發生。如果有和解機會，我們肯定會與他們接觸。

Our next question comes from the line of Gregory Renza from RBC Capital Markets.

我們的下一個問題來自加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Gregory Renza。

Mike and team, congrats on the progress. Mike, maybe just a question for Amy. I know first time hearing from Amy and Amy, you're really diving right into the Exelixis pipeline, and we look forward to the data and the R&D Day coming up. Just wanted to give you an opportunity to talk a bit about the opportunities you see here with the pipeline and also perhaps some of the challenges that you think are ahead of you in order to realize the value that you're talking about in the portfolio and the pipeline.

麥克和他的團隊，祝賀你們的進展。麥克，也許只是問艾米一個問題。我知道第一次收到 Amy 和 Amy 的來信，你們確實在深入研究 Exelixis 管道，我們期待著數據和研發日的到來。只是想讓您有機會談談您在這裡看到的管道機會，以及您認為面臨的一些挑戰，以便實現您在投資組合中談論的價值，以及管道。

All right. Well, thanks, Greg, for the question. I appreciate it, and thanks for the welcome. I'm really excited to be here. I think one of the reasons -- the main reason I'm excited to be here is because of the pipeline that Exelixis has and the opportunity to apply my development skills and the company's development skills into bringing all of these assets into the limelight and to fully develop them where they warrant more development. I'm particularly excited about zanza. I think the data that is emerging is demonstrating that it's a best in class. And again, we'll be able to share more of that at R&D Day.

好的。嗯，謝謝格雷格提出的問題。我很感激，也感謝你們的歡迎。我很高興來到這裡。我認為原因之一 - 我很高興來到這裡的主要原因是因為 Exelixis 擁有的管道以及應用我的開發技能和公司的開發技能將所有這些資產帶到聚光燈下並實現的機會在他們需要更多發展的地方充分發展他們。我對贊扎特別興奮。我認為正在出現的數據表明它是同類中最好的。同樣，我們將能夠在研發日分享更多內容。

And I think our tissue factor ADC is differentiated from the Tivdak molecule in a couple of different ways, most notably in the payload and so the tax profile should be different. So we have opportunities there. And with the USB 1 inhibitor that's the just entering clinic, that's a best-in-class asset, we believe. And as I mentioned in the call, the opportunity to not only deepen the responses seen, for example, in combination with PARP inhibition. And so to further improve those patients, who might drive benefit with PARP inhibitor, but also to broaden the accessible patient population beyond those with BRCA mutations.

我認為我們的組織因子 ADC 與 Tivdak 分子在幾個不同的方面有所不同，最顯著的是在有效負載方面，因此稅收概況應該有所不同。所以我們在那裡有機會。我們相信，對於剛進入臨床的 USB 1 抑制劑來說，這是一項一流的資產。正如我在電話中提到的，不僅有機會加深所看到的反應，例如與 PARP 抑制相結合。因此，為了進一步改善那些可能透過 PARP 抑制劑獲益的患者，同時也將可接觸的患者群體擴大到 BRCA 突變患者之外。

So there's a lot of really exciting opportunities for Exelixis in the future. It's hard to focus on any one of them, but I absolutely will be focused on each of them.

因此，Exelixis 未來有很多令人興奮的機會。很難專注於其中任何一個，但我絕對會專注於他們每一個。

Our next question comes from the line of Jay Olson from Oppenheimer.

我們的下一個問題來自奧本海默的傑伊·奧爾森（Jay Olson）。

Congrats on the progress. For CONTACT-02, can you talk about when the next OS analysis might happen based on your modeling. And then also, can you file the sNDA without OS? And how would you describe clinically meaningful benefits for PFS and OS in this particular setting? And where do you see cabo plus atezo fitting into the treatment landscape?

祝賀取得的進展。對於 CONTACT-02，您能否談談根據您的建模何時可能進行下一次作業系統分析。另外，您可以在沒有作業系統的情況下提交 sNDA 嗎？您如何描述在這種特定情況下 PFS 和 OS 具有臨床意義的益處？您認為 cabo plus atezo 適合治療領域的哪些面向？

So Amy, let's take the first part of that question and then maybe P.J. can kind of frame the commercial opportunity at a super high level.

艾米，讓我們回答這個問題的第一部分，然後也許 P.J. 可以在超高水平上建立商業機會。

Yes. Great. Thanks, Jay. I appreciate the question. So OS is event driven based on current estimates, we believe the final OS would occur sometime in 2024. I'm really not at liberty to talk much more about that. As for clinical meaningfulness of PFS, it's a totality of the data, and I'm not going to speculate on what a PFS difference has to be, but rather just remind the patients that were enrolled into this study represent a very poor prognostic group of patients. These are patients, who must have had measurable disease, and that included patients with liver disease, patients with extranodal visceral disease. So a group of patients that otherwise don't have many options available to them. And it's the totality of the data. So not just improvements in PFS, but also tolerability and accessibility and ease of delivering the therapy. And I think with that, I'll let P.J. talk about the commercial opportunity.

是的。偉大的。謝謝，傑伊。我很欣賞這個問題。因此，根據當前的估計，作業系統是事件驅動的，我們相信最終的作業系統將在 2024 年的某個時候出現。我真的無權過多談論這一點。至於 PFS 的臨床意義，它是數據的總體，我不會推測 PFS 的差異是什麼，而只是提醒參加這項研究的患者代表了一個預後非常差的群體。患者。這些患者必須患有可測量的疾病，其中包括患有肝病的患者、患有結外內臟疾病的患者。因此，這群患者沒有太多選擇。這是數據的整體。因此，不僅改善了 PFS，也改善了治療的耐受性、可近性和便利性。我想接下來我會讓 P.J. 談談商業機會。

Great. Yes. Thanks, Amy, and thanks for the question, Jay. I think as Amy highlighted, this is an area of certainly high unmet medical need for patients. So that's really important, and we've heard that from KOLs all along. I think if you think about how this regimen could potentially fit in, right now, obviously, the majority of patients in the first-line metastatic castration-resistant prostate setting are getting an NHT. And then beyond that, you've got subsequent NHT chemo and obviously, the study addresses patients relative to a second NHT. So there's that data. But then beyond that, chemo, I think, it's something that physicians and their patients we hear consistently really want to delay in treatment.

偉大的。是的。謝謝艾米，也謝謝傑伊的提問。我認為正如艾米所強調的那樣，這對患者來說無疑是一個未被滿足的醫療需求很高的領域。所以這非常重要，我們一直從 KOL 那裡聽到這一點。我認為，如果你考慮一下這種治療方案如何可能適合目前的情況，顯然，目前一線轉移性去勢抵抗性前列腺治療中的大多數患者都在接受 NHT。除此之外，還有後續的 NHT 化療，顯然，研究針對的是與第二次 NHT 相關的患者。所以就有了這些數據。但除此之外，我認為，我們一直聽到醫生和病人確實希望延後化療。

So I think a chemo-less option could potentially really help that in this setting. And then also, these are 2 novel mechanisms of action potentially again for the prostate cancer setting. So I think any time there's a lot of excitement for new MOAs in a disease setting and certainly, in a setting where there's no broadly available immunotherapy agent, there will certainly be a lot of excitement should this get approved for that as well. So I think you would potentially see cabo-atezo used prior to chemo and across multiple lines of therapy depending on the patient.

所以我認為，在這種情況下，無化療的選擇可能會真正有所幫助。此外，這兩種新的作用機轉也可能適用於攝護腺癌。因此，我認為任何時候在疾病環境中都會對新的MOA 產生很大的興奮，當然，在沒有廣泛可用的免疫療法藥物的環境中，如果它也獲得批准，肯定也會有很多令人興奮的事情。因此，我認為您可能會看到在化療前使用 cabo-atezo，並根據患者的情況進行多線治療。

Our next question comes from the line of Jing Deng from Truist.

我們的下一個問題來自《Truist》中鄧景的台詞。

This is Jing on the line for Asthika from Truist. I have one question regarding about how you view the impact of the recent approval of belzutifan which is HIF-2 alpha inhibitor from Merck. They are trying to launch this drug in second line RCC, where we know the cabo has a very strong presence. So yes, so I want to ask you, do you expect that this drug will be capture a significant share of the market and how do you plan to differentiate cabo from other drugs?

我是 Jing，正在接聽來自 Truist 的 Asthika。我有一個問題，關於您如何看待最近批准的 Belzutifan（一種來自默克公司的 HIF-2 α 抑制劑）的影響。他們正試圖在二線 RCC 中推出這種藥物，我們知道 cabo 在那裡有非常強大的影響力。所以是的，所以我想問您，您是否預計這種藥物將佔據相當大的市場份額？您計劃如何將 cabo 與其他藥物區分開來？

Okay. Thanks for the question, Amy, P.J., do you want to take that one?

好的。謝謝你的提問，艾米，P.J.，你想接受那個嗎？

Yes, Jing, thanks for the question. I assume you're referring to the recently presented LITESPARK data at ESMO. So obviously, no approval for that data yet with the HIF inhibitor. And really, I think it's important to realize and contextualize that, that study is really in a later line setting in patients, who have received IO and TKI that was head-to-head with everolimus. It didn't have an OS benefit. We've had certainly a lot of discussions already with KOLs at ESMO and beyond about the data. And what we really see is that having likely competing in very late lines of therapy in RCC setting, predominantly with tivozanib. So we don't see any significant impact with regards to the cabo business generally or our second-line business.

是的，Jing，謝謝你的提問。我假設您指的是 ESMO 最近提供的 LITESPARK 資料。顯然，HIF 抑制劑的數據尚未獲得批准。事實上，我認為重要的是要認識到並結合實際情況，這項研究實際上是在患者中進行的，這些患者接受了與依維莫司正面交鋒的 IO 和 TKI 治療。它沒有作業系統優勢。當然，我們已經與 ESMO 及其他領域的 KOL 就數據進行了許多討論。我們真正看到的是，在 RCC 環境中，很可能在非常晚期的治療中競爭，主要是與 tivozanib 競爭。因此，我們認為卡波業務或我們的二線業務不會受到任何重大影響。

Our next question comes from the line of Andy Hsieh from William Blair.

我們的下一個問題來自威廉布萊爾 (William Blair) 的安迪謝 (Andy Hsieh)。

Amy, congratulations on your new role and look forward to working with you. So first of all, really pleased to see the first positive IO containing regimen in prostate cancer. So there's a lot of moving pieces in the field. Just curious if you can give us a sense of what the FDA is looking for pertaining to OS, right? I guess if you look at the Novartis PSMA4 that allows for crossover. It sounds like they want to look for something along the lines of no detriment there. Is the bar higher for CONTACT-02, just given the no crossover nature? So that's number one.

艾米，祝賀您擔任新職務，並期待與您合作。首先，我很高興看到第一個針對攝護腺癌的正向 IO 治療方案。因此，這個領域有很多變化。只是好奇您能否讓我們了解 FDA 正在尋找與作業系統相關的內容，對吧？我想如果您看看允許交叉的諾華 PSMA4。聽起來他們想在那裡尋找一些無害的東西。鑑於無交叉特性，CONTACT-02 的標準是否較高？所以這是第一。

And then kind of staying within the GU space, this morning, KEYNOTE-564 OS benefit in the adjuvant setting, I'm curious about your view on that regarding its impact to the first-line metastatic market? And whether you have plans to kind of navigate through that market evolution?

然後留在 GU 領域，今天早上，KEYNOTE-564 OS 在輔助設定中受益，我很好奇您對其對一線轉移市場的影響有何看法？您是否有計劃應對市場演變？

Thanks, Andy, lets have Amy take the first part or the first question, and then P.J. can talk about adjuvant. Okay. Amy?

謝謝，安迪，讓艾米回答第一部分或第一個問題，然後 P.J. 可以談談佐劑。好的。艾米？

Yes, sure. So I appreciate the question and the complexity behind it. I can't pretend to say what the agency is actually looking for. What I can say is that it's not inconsistent with the feedback that other companies are getting and they just want to see some more mature OS data. So I'll keep you posted as that progresses. Stay tuned.

是的，當然。所以我很欣賞這個問題及其背後的複雜性。我無法假裝說出該機構真正在尋找什麼。我能說的是，這與其他公司得到的回饋並不矛盾，他們只是想看到一些更成熟的作業系統數據。因此，我會隨時向您通報進度。敬請關注。

Andy, thanks for the question. With regards to the 564 study in the adjuvant setting, as you know, that data was presented originally years ago and has been on the market for some time. The original OS hazard ratio, while not mature, was quite impressive, so to speak. So this is really no surprise. I think that these data were positive. I think it's important to remember that this sort of high-risk population as defined by the study is quite small relative to the number of patients who get an nephrectomy in a given year. So we're talking just a few thousand patients. And I think that's already been working its way through the treatment algorithm with regards to those patients recurring in the first-line setting. So we have a pretty good feel for that.

安迪，謝謝你的提問。關於輔助治療中的 564 研究，如您所知，該數據最初是幾年前提供的，並且已經上市一段時間了。可以說，最初的作業系統風險比雖然還不成熟，但相當令人印象深刻。所以這確實不足為奇。我認為這些數據是正面的。我認為重要的是要記住，研究定義的此類高風險族群相對於特定年份接受腎切除術的患者數量來說相當小。所以我們談論的只是幾千名患者。我認為，對於那些在一線環境中復發的患者，治療演算法已經在發揮作用。所以我們對此有很好的感覺。

Really haven't seen much of a significant impact to date. What we do here is patients who potentially recur while on pembro or relatively shortly after pembro in the adjuvant setting, many physicians do sort of think of them as refractory, so to speak, to checkpoint inhibition. And often then that leads them to consider a TKI monotherapy in the first-line setting. And obviously, with cabo on and the totality of our data, we're well positioned for those patients. I think overall, with OS, certainly, a few more physicians will prescribe that, but we really don't see much of a significant impact in the first-line setting. And obviously, these things take years to develop, but we've kind of been in it now for a couple of years and pretty comfortable with that analysis.

到目前為止，確實還沒有看到太大的重大影響。我們在這裡所做的是那些在使用 pembro 時或在輔助治療中使用 pembro 後不久可能複發的患者，許多醫生確實認為他們對檢查點抑制具有難治性。這通常會導致他們考慮在一線環境中使用 TKI 單一療法。顯然，隨著 Cabo 的開啟和我們的全部數據，我們已經為這些患者做好了準備。我認為總體而言，對於 OS，當然會有更多的醫生會開這種處方，但我們確實沒有看到對第一線環境有太大的重大影響。顯然，這些東西需要數年的時間來開發，但我們現在已經投入了幾年，並且對這種分析非常滿意。

Great. Thank you, P.J. and thank you, Andy, for the questions. Operator, we'll take the next question, please.

偉大的。謝謝你，P.J.，謝謝你，安迪，提出問題。接線員，我們將回答下一個問題。

Our next question comes from the line of Yaron Werber from TD Cowen.

我們的下一個問題來自 TD Cowen 的 Yaron Werber。

Great. And nice job on the case last week. My question has to do -- and I know you can't comment on what you think the outcome would be. But can you maybe just comment that the judge did give some specifics on the next steps in terms of the initial briefs, response briefs and the reply briefs, which are due February 20. Do you -- maybe just kind of generically procedurally, can you help us understand the timing, the way you see it a little bit? Does that mean that the judge has a certain amount of time after the reply brief to then render a decision or give a timeline by which you will render a decision or just so we understand procedurally how you understand things to be?

偉大的。上週這個案子做得很好。我的問題是——我知道你不能評論你認為的結果。但您能否評論一下，法官確實就初步簡報、答复簡報和答复簡報等後續步驟給出了一些具體細節，這些簡報將於2 月20 日到期。您是否——也許只是一般性的程序，您可以嗎？幫助我們理解這個時機，你是怎麼看待它的？這是否意味著法官在簡短答覆後有一定的時間做出決定，或者給出一個時間表讓您做出決定，或者只是讓我們在程序上了解您是如何理解事情的？

Yes, Yaron. Thanks for the question. It's really hard for me to opine upon the nuances and details there. I would refer you back to the transcript to see exactly what he asked for and what he's looking for. To me, it seemed like pretty standard stuff with how this stuff normally works. But I wouldn't want to get in the weeds there in the details. It's just, A, I'm not an expert; and b, it's just -- I want to keep it with what's in the public domain, what's in the transcript and not really opine for this.

是的，亞龍。謝謝你的提問。我真的很難對其中的細微差別和細節發表意見。我會請您回顧一下文字記錄，以準確了解他的要求和他正在尋找的內容。對我來說，這似乎是非常標準的東西，而且這些東西通常是如何運作的。但我不想糾纏細節。只是，A，我不是專家； b，這只是——我想將其與公共領域、記錄中的內容一起保留，而不是真正對此發表意見。

Our next question comes from the line of Akash Tewari from Jefferies.

我們的下一個問題來自 Jefferies 的 Akash Tewari。

This is Amy on for Akash. So just 2 quick ones on zanza. Number one, when will we get longer-term durability data on zanza that we can compare versus cabo? Will we be able to get a sense of this from the upcoming STELLAR-001 data?

這是艾米為阿卡什主持的節目。所以在 zanza 上只有 2 個快速的。第一，我們什麼時候才能獲得 zanza 的長期耐用性數據，以便與 cabo 進行比較？我們能否從即將發布的 STELLAR-001 數據中了解這一點？

And then number two, given that both mono and combo efficacy data for zanza looks generally in line with cabo. We'd love to kind of revisit your internal goals here for zanza given it's sort of half-life. Is it to replace cabo and show a better safety and efficacy profile or to expand into new indications?

然後是第二點，因為 zanza 的單藥和組合功效數據看起來與 cabo 基本一致。鑑於贊札的半衰期，我們很樂意重新檢視您的內在目標。是為了取代 Cabo 並顯示出更好的安全性和有效性，還是擴展到新的適應症？

Yes. Sure. Thanks for the question, Amy. I like your name. So as for the longer durability, I think you'll be able to appreciate why it is that we're excited about zanza when the -- after the IKCS presentation on November 10, and if you're not able to see that, then certainly at R&D Day where I'll go into some more detail.

是的。當然。謝謝你的提問，艾米。我喜歡你的名字。因此，至於更長的耐用性，我想您將能夠理解為什麼我們對 zanza 感到興奮——在 11 月 10 日的 IKCS 演示之後，如果您看不到這一點，那麼當然在研發日我會詳細介紹。

With regard to the 001 and 002 cohorts, many of those cohorts are enrolled and the data is maturing. There's a number of different indications that we are assessing for support to our expanded program, our expanded development program, not only to give support to what we're currently doing and to support, for example, contribution of components as we proceed with regulatory discussions, should those trials be positive, but also support to expand the development of zanza into new and different indications, and that's where we'll also leverage cabo.

至於001和002隊列，其中許多隊列已入組且資料正在成熟。有許多不同的跡象表明，我們正在評估對我們的擴展計劃、擴展開發計劃的支持，不僅是為了支持我們目前正在做的事情，而且是為了支持，例如，在我們進行監管討論時提供組件貢獻，如果這些試驗是積極的，並且還支持將zanza 的開發擴展到新的和不同的適應症，這也是我們將利用cabo 的地方。

So I can't go into much more detail, but I will be able to probably give you some good examples of why we're pretty bullish on zanza at this point in time given what we know about yet relative to cabo. And with regard to replacing cabo, I'll defer that back to Mike or P.J.

因此，我無法透露更多細節，但我可能會給您一些很好的例子，說明為什麼我們目前對 zanza 非常看好，因為我們對 cabo 的了解還不夠。至於更換 cabo，我會將其交給 Mike 或 P.J.

Yes, I think you covered it pretty well. Again, just as we said previously, the goal here is to use zanza to expand the indications, the combinations, the line of therapy, if you will. And [cabo] sensitive types of tumors and indications, the goal is to make that opportunity for zanza as big as possible across the different dimensions that we're talking about here. So it's a very important aspiration that we have that we think we can help a lot more cancer patients, who need better therapies across the different lines of therapy, early, late, different combination partners, et cetera. .

是的，我認為你講得很好。再次強調，正如我們之前所說，如果您願意的話，這裡的目標是使用 zanza 來擴大適應症、組合和治療範圍。對於敏感類型的腫瘤和適應症，我們的目標是在我們在這裡討論的不同維度上為 zanza 提供盡可能大的機會。因此，我們有一個非常重要的願望，我們認為我們可以幫助更多的癌症患者，他們需要跨越不同治療線、早期、晚期、不同的聯合療法等更好的治療。 。

Our next question comes from the line of Silvan Tuerkcan from JMP Securities.

我們的下一個問題來自 JMP 證券的 Silvan Tuerkcan。

Congrats on the quarter. And Amy congrats on the new job. I have a quick question. In the press release, it seems like you released that COSMIC-313, so the triplet had a second OS look, which did not meet the threshold for that statistical significance. Can you just comment on when the next OS look is? And what we can extrapolate from the fact that the second OS look did not meet the threshold? What are the prospects here? And what are the plans as in the OS look with respect to filing and engaging with the FDA about these 2 populations that have different outcomes here in this trial?

恭喜本季。艾米祝賀你找到新工作了。我有一個快速的問題。在新聞稿中，您似乎發布了 COSMIC-313，因此三元組有第二個作業系統外觀，但未達到統計顯著性的閾值。您能否評論一下下一個作業系統的外觀是什麼時候？我們可以從第二個作業系統外觀未達到閾值的事實中推斷出什麼？這裡的前景如何？對於在本次試驗中具有不同結果的這兩個人群，OS 有何計劃向 F​​DA 提交申請並與 FDA 合作？

Amy?

艾米？

Yes Thanks, Mike. Thanks, Silvan. So we did a press release that there was an interim that was conducted in the third quarter. Data did not meet the threshold for statistical significance. And so the trial will continue to the next planned analysis, which is anticipated in 2024. Just to remind everybody that these are event-based and I'm not really able to provide further precision on that at this point in time. And so I don't really have much more to say around that.

是的，謝謝，麥克。謝謝，西爾萬。因此，我們發布了一份新聞稿，稱第三季進行了一次臨時調整。數據未達統計顯著性閾值。因此，試驗將繼續進行下一次計畫分析，預計在 2024 年進行。只是提醒大家，這些都是基於事件的，目前我無法提供進一步的精確資訊。所以我對此沒什麼好說的。

Operator, we're happy to take the next question.

接線員，我們很高興回答下一個問題。

Our next question comes from the line of Peter Lawson from Barclays.

我們的下一個問題來自巴克萊銀行的彼得勞森。

Mike, you mentioned no new data at the R&D Day. Would you include kind of preclinical data around the new pipeline products? And then will you include timelines around data releases for '24 for the pipeline?

麥克，你提到研發日沒有新數據。您會提供有關新管道產品的臨床前數據嗎？然後您會在管道中包含 '24 資料發布的時間表嗎？

Thanks, Peter, for the question and for digging into the details for the December meeting. Yes, I was speaking to no new clinical data. You'll certainly see, I think, a lot of preclinical data that Dana will present and use to frame the opportunities for all the upcoming IND candidates and DC candidates that we've got best relatively broad and deep, and we have a lot to share there.

感謝 Peter 提出問題並深入探討 12 月會議的細節。是的，我所說的並不是新的臨床數據。我想，你肯定會看到Dana 將展示並使用的大量臨床前數據來為所有即將推出的IND 候選者和DC 候選者構建機會，我們已經獲得了相對廣泛和深入的信息，並且我們還有很多東西可以做在那裡分享。

Time lines, again, we'll see how that frames out. Again, both we're committed to presenting clinical data as it matures, that is in the eye of the beholder in terms of how that works from a duration and durability point of view. So stay tuned on that. And again, we have very, I think, deep presentation that we're pulling together right now that covers all the aspects of strategically how we view success and how we're going to go about reaching these very aspirational goals for helping improve standard of care of patients with cancer and then a lot of details and really getting in the weeds on a variety of different molecules that we're really excited about. So looking forward to seeing you there.

時間線，我們將再次看看它是如何發展的。同樣，我們都致力於提供成熟的臨床數據，從持續時間和持久性的角度來看，這是情人眼中的效果。所以請繼續關注。我認為，我們現在正在一起進行非常深入的演示，涵蓋了我們如何看待成功的策略以及我們將如何實現這些非常理想的目標，以幫助提高照顧癌症患者，然後是很多細節，真正深入了解我們真正興奮的各種不同分子。期待在那裡見到您。

Our next question comes from the line of Jeff Hung from Morgan Stanley.

我們的下一個問題來自摩根士丹利的 Jeff Hung。

Can you talk about what differentiates XL495 from other PKMYT1 inhibitors in development? And what gives you confidence that it can be best in class? Is it greater selectivity, potency, lower risk of drug-drug interactions or something else? I appreciate any color you can provide.

您能否談談 XL495 與其他正在開發的 PKMYT1 抑制劑有何不同？是什麼讓您有信心它可以成為同類中最好的？是更高的選擇性、效力、更低的藥物交互作用風險還是其他？我很感激你能提供的任何顏色。

Sure. Thanks for the question, Jeff. This is Dana. So as I mentioned, XL495, we believe to be best-in-class. We don't say that lightly. We have a lot of data to back that up. All I really want to say right now is to stay tuned for R&D Day, which is where we will be presenting a lot more data on this compound. But we did look at the competition and pursued a very solid rationale toward developing something that was best-in-class, not just a second follow-on compound.

當然。謝謝你的提問，傑夫。這是達納。正如我所提到的，我們相信 XL495 是同類中最好的。我們不會輕易這麼說。我們有大量數據來支持這一點。我現在真正想說的是繼續關注研發日，我們將在這一天展示更多有關該化合物的數據。但我們確實關注了競爭，並尋求一個非常堅實的理由來開發同類最佳的產品，而不僅僅是第二種後續化合物。

Our next question comes from the line of Etzer Darout from BMO Capital Markets.

我們的下一個問題來自 BMO 資本市場的 Etzer Darout。

Great. So thank you for laying out sort of the IND plans for Exelixis. But just wondered if you could comment at all on sort of the Phase I assets that you have in development and maybe for 2024, where we could see potential proof of concept in the clinic with assets like CBX-12, the ADU-1805 compound and some of the other assets that you have in Phase I, early clinical trial, I guess, is sort of where we could see potential proof of concept there?

偉大的。感謝您為 Exelixis 制定了 IND 計畫。但只是想知道您是否可以對您正在開發的一期資產發表評論，也許是在 2024 年，我們可以在臨床中看到潛在的概念證明，包括 CBX-12、ADU-1805 化合物和我想，你們在第一階段、早期臨床試驗中擁有的其他一些資​​產，是我們可以看到潛在概念證明的地方？

Etzer, thanks. It's Amy. I'll take that. So we do have some other assets that are partnered that are in Phase I, and we are actively always looking at the data, and we'll make database decisions on how those progress and move forward. But those are good partnerships with our XB002 that is advancing into its expansion cohorts. I would say we're in the process of understanding really proof of developability and the way I differentiate proof of concept from proof of developability is proof of concept, you have a couple of responses, and it's interesting or you get a pharmacodynamic marker, it looks like the drug is doing something to the tissue in the human, but you don't yet know how to move that into a pivotal study. These expansion cohorts for XB002 will actually -- are designed to actually inform us if we see a certain amount of activity, how would we move into pivotal studies.

埃澤爾，謝謝。是艾米。我會接受的。因此，我們確實有一些其他處於第一階段的合作資產，我們一直在積極地查看數據，我們將就這些進展和進展做出資料庫決策。但這些都是與我們的 XB002 的良好合作夥伴關係，XB002 正在進入其擴展隊列。我想說，我們正在真正理解可開發性證明，我區分概念證明和可開發性證明的方式是概念證明，你有幾個反應，這很有趣，或者你得到一個藥效標記，它看起來該藥物正在對人體組織產生作用，但您還不知道如何將其轉移到關鍵研究中。 XB002 的這些擴展隊列實際上旨在告訴我們，如果我們看到一定程度的活動，我們將如何進入關鍵研究。

And so those expansion cohorts are enrolling when they mature. And when we have that data, it's just dependent on how long it takes for the responses and the durability of the responses. So we could have some things in 2024.

因此，這些擴張群體在成熟時就會招收。當我們擁有這些數據時，它僅取決於回應所需的時間以及回應的持久性。所以我們可以在 2024 年實現一些目標。

And then for XL, the USP1 inhibitor, right, that's just getting started. And as we transfer that in and we go through dose escalation, I think we'll have a better understanding of what we need to see in terms of proof of developability there. I think we already have a good head start, understanding the patient population that is most likely to respond to this sort of an agent and harnessing that knowledge in terms of our eligibility criteria will help us understand how we might quickly move into full development with that asset. And I think I'm not -- I'll stop there.

然後對於 XL，USP1 抑制劑，對吧，這才剛開始。當我們將其轉移並經歷劑量遞增時，我認為我們將對我們需要在可開發性證明方面看到的內容有更好的理解。我認為我們已經有了一個良好的開端，了解最有可能對此類藥物產生反應的患者群體，並根據我們的資格標準利用這些知識將有助於我們了解如何快速進入全面發展階段資產。我想我不會——我就到此為止。

All right, Amy. Thank you. Operator, we'll take the next question.

好吧，艾米。謝謝。接線員，我們將回答下一個問題。

Our next question comes from the line of Chris Shibutani from Goldman Sachs.

我們的下一個問題來自高盛的 Chris Shibutani。

This is Stephen on for Chris. Two from us. On cabinet, the data that was presented at ESMO showed quite a clear PFS benefit, though the OS curves didn't separate as much. So I guess in that light, how confident are you that regulators will view that data package as an approval data set? And then on XL309 recently in-licensed, can you speak to what gives you confidence that, that could be a best-in-class asset among competitive USP1 inhibitors?

這是克里斯的史蒂芬。我們兩個。在機櫃方面，ESMO 上提供的數據顯示出相當明顯的 PFS 優勢，儘管 OS 曲線分離得不太明顯。因此，我想從這個角度來看，您對監管機構將該資料包視為批准資料集的信心有多大？那麼關於最近獲得許可的 XL309，您能否談談是什麼讓您有信心它可能成為競爭性 USP1 抑製劑中的同類最佳資產？

Okay. Good. So Amy, why don't you take the CABINET question and then Dana can speak to 309.

好的。好的。那麼艾米，你為什麼不接受內閣提問，然後達納就可以撥打 309。

Yes. Thanks for the question, Stephen. It's an important question to bring up, because the way the study was designed is that crossover was allowed and the study was unblinded early due to the significant benefit in progression-free survival that was observed and all patients at that point in time were crossed over. So there's not really an expectation for survival -- for us to observe survival. Whether or not that passes the test of the agency is discussion we'll have. We're pretty optimistic given that this is such a rare disease and a high unmet need in late lines of setting where patients really have nothing else available to them. So we're optimistic. But again, we have yet to have that initial discussion.

是的。謝謝你的提問，史蒂芬。這是一個需要提出的重要問題，因為該研究的設計方式是允許交叉的，並且由於觀察到無進展生存期的顯著益處並且該時間點的所有患者都被交叉，所以該研究很早就是非盲的。 。因此，我們並沒有真正期望生存──觀察生存。是否通過該機構的測試是我們將要討論的問題。我們非常樂觀，因為這是一種罕見的疾病，在晚期患者確實沒有其他治療方法的情況下，未滿足的需求很高。所以我們很樂觀。但同樣，我們還沒有進行初步討論。

Great. Dana, 309.

偉大的。達納，309。

Yes, thanks for the questions, Stephen. Regarding 309. So even though that's an in-licensed compound, we actually did quite a bit of experimental work ourselves in our own labs with that molecule. We have quite a data set that supports our statement that we believe it to be best-in-class. And so similar to what I said about XL495, we're planning to give a lot more detail at R&D Day. So I would just say stay tuned for the update there, we will see a lot more -- you'll get a lot more information on the molecule.

是的，謝謝你的提問，史蒂芬。關於 309。因此，儘管這是一種獲得許可的化合物，但我們實際上在自己的實驗室中用該分子做了相當多的實驗工作。我們有相當多的數據集支持我們的說法，即我們相信它是同類最佳的。與我對 XL495 所說的類似，我們計劃在研發日提供更多詳細資訊。所以我想說，請繼續關注那裡的更新，我們會看到更多——您將獲得更多有關該分子的信息。

All right. Thanks, Dana.

好的。謝謝，達納。

Our next question comes from the line of Joe Catanzaro from Piper Sandler.

我們的下一個問題來自 Piper Sandler 的 Joe Catanzaro。

Maybe just a quick one for me. So Amy, I know you have some ADC experience in some prior roles. So just wondering how you think about the next-gen topo 1 tissue factor ADC that you guys have in the pipeline relative to XB002 and maybe more generally, how you think about auristatin and tubulin-based payloads versus topoisomerase-based payloads and maybe how you develop these 2 programs sequentially?

也許對我來說只是一個快速的過程。艾米，我知道您在之前的一些角色中擁有一些 ADC 經驗。因此，我只是想知道您如何看待您正在開發的相對於XB002 的下一代拓撲1 組織因子ADC，也許更一般地說，您如何看待基於auristatin 和微管蛋白的有效負載與基於拓撲異構酶的有效負載，以及您如何看待依序開發這2個程式？

Hi, Joe, thanks very much for the question. Thanks for the welcome. Yes, I definitely have some experience in ADCs. So with regard to the topo 1 payload, I think it's actually an opportunity to take a molecule into tumors that both express tissue factor and are sensitive to topoisomerase inhibition, so not all tumors that express tissue factor are sensitive to anti-tubulins like auristatin. So adding a different payload actually allows us to potentially cast a wider net with regard to some of the tumors that we might pursue. And, of course, would offer a differentiated toxicity profile.

你好，喬，非常感謝你的提問。感謝您的歡迎。是的，我確實有一些 ADC 經驗。所以關於topo 1有效負載，我認為這實際上是一個將分子帶入既表達組織因子又對拓撲異構酶抑制敏感的腫瘤的機會，因此並非所有表達組織因子的腫瘤都對像auristatin這樣的抗微管蛋白敏感。因此，添加不同的有效負載實際上使我們能夠針對我們可能追求的一些腫瘤撒下更廣泛的網。當然，也會提供不同的毒性特徵。

When it comes to the auristatin versus MMAEs, there are certain toxicities that are similar, for example, (inaudible), but there are other toxicities that aren't as similar between our payload and what you might expect from Tivdak. So neuropathy and bleeding is not something that we would expect to see with ours. So the payload is different for our XB002 than what is with Tivdak. We're already starting to have a differentiated toxicity profile. We're excited about the data that Tivdak has shown, and that offers us an opportunity to think about how we might bring XB002 forward into that space, leveraging our differentiated toxicity profile. So I hope that answered your question.

例如，當涉及到 auristatin 與 MMAE 時，某些毒性是相似的（聽不清楚），但我們的有效負載與您可能從 Tivdak 獲得的毒性之間還有其他毒性並不相似。因此，神經病變和出血並不是我們所期望的。因此，我們的 XB002 的有效負載與 Tivdak 的有效負載不同。我們已經開始有不同的毒性特徵。我們對 Tivdak 展示的數據感到興奮，這為我們提供了一個機會來思考如何利用我們差異化的毒性特徵將 XB002 推向該領域。所以我希望這回答了你的問題。

Our next question comes from the line of Stephen Willey from Stifel.

我們的下一個問題來自 Stifel 的 Stephen Willey。

Just a couple of quick clinical ones for me. So on STELLAR-305, I'm just kind of curious, I know Merck announced the LEAP-10 trial didn't hit its endpoint, I guess, a couple of months ago. And just curious how you think about zanza differentiation relative to lapatinib within the setting of head and neck?

對我來說，只有幾個快速的臨床方法。所以對於 STELLAR-305，我只是有點好奇，我知道默克公司宣布 LEAP-10 試驗沒有達到終點，我想是在幾個月前。只是好奇您如何看待贊札相對於拉帕替尼在頭頸部環境中的差異化？

And then maybe just a quick follow-up to Joe's question. I know for JEWEL-101, you're not looking at cervical as part of any of the combination expansion cohorts, and I guess just kind of given some of the concern around combining Tivdak with the overlapping bleeding risk. Just kind of curious why that's not on your radar screen right now?

然後也許只是對喬的問題進行快速跟進。我知道對於 JEWEL-101，您並沒有將子宮頸視為任何組合擴展隊列的一部分，我想這只是考慮到將 Tivdak 與重疊出血風險相結合的一些擔憂。只是有點好奇為什麼現在你的雷達螢幕上沒有這個？

Okay. Amy, let's handle -- maybe handle the second question first, just to clear up that misconception.

好的。艾米，讓我們來處理——也許先處理第二個問題，只是為了澄清這個誤解。

Yes. Clear that up, cervical cancer is in our list of expanded cohorts for JEWEL-101. We are absolutely investing in it. And then with regard to STELLAR-305, what gives us confidence, even though pem-len didn't quite hit the mark is the data that was generated with cabo-pem in the study of 33 patients where we had a 54% response rate and a PFS of 14.6 months. We think that, that benchmarks favorably to what len-pem showed in their Phase II, which was an ORR of 36% and a PFS of 8.2 months. So we're different. So that was cabo-pem, this is what we're bringing forward is zanza-pem, which is what we believe to be a best-in-class and better than what we could have observed with cabo and already cabo-pem in cross-trial comparisons looks to be better than pem-len. So I hope that answers it.

是的。需要澄清的是，子宮頸癌在我們的 JEWEL-101 擴展隊列列表中。我們絕對會投資它。然後，關於 STELLAR-305，儘管 pem-len 沒有完全達到目標，但給我們信心的是在 33 名患者的研究中使用 cabo-pem 產生的數據，我們的緩解率為 54% PFS 為 14.6 個月。我們認為，該基準優於 len-pem 在第二階段的表現，即 ORR 為 36%，PFS 為 8.2 個月。所以我們不一樣。這就是 cabo-pem，這就是我們提出的 zanza-pem，我們認為這是同類中最好的，比我們在 cabo 和已經交叉的 cabo-pem 中觀察到的更好- 試驗比較看起來比pem- len 更好。所以我希望這能回答這個問題。

Our next question comes from the line of Christopher Liu from Leerink Partners.

我們的下一個問題來自 Leerink Partners 的 Christopher Liu。

So you mentioned that during the R&D Day, it's going to be focused a lot on the science. Just wondering if there's any color you can give us in terms of when we can expect to see data for some of these pipeline assets like tissue factor in ADC, the CDK7, the USP 1 that you recently in-licensed, anything on that?

所以你提到在研發日期間，它將專注於科學。只是想知道您是否可以給我們任何信息，說明我們何時可以看到其中一些管道資產的數據，例如 ADC 中的組織因子、CDK7、您最近獲得許可的 USP 1 等？

And then in terms of -- just a quick second question. In terms of business development, are you guys looking to -- are you guys looking at assets that are earlier in the clinical stage? Or would you guys consider something later on in the clinical stage as well?

然後就——只是第二個問題。在業務發展方面，你們是否正在尋找早期臨床階段的資產？或者你們會在臨床階段後期考慮一些事情嗎？

Yes. Thanks for the questions, Chris. It's my comments for both questions. Starting with the question. First, look, we're a very interested looking for molecules that are clinical stage assets early stage, mid-stage and late stage that have the data that help us understand the potential for both clinical and commercial differentiation, right? So that can be early, that can be late. Again, we have to be -- we have to have the right level of conviction that what we're looking at and potentially either partnering or acquiring can really move the needle for patients because, again, the [cabo-len], that's the only way we're going to be able to build value in this very, very competitive marketplace.

是的。謝謝你的提問，克里斯。這是我對這兩個問題的評論。從問題開始。首先，我們非常有興趣尋找早期、中期和晚期臨床階段資產的分子，這些分子的數據可以幫助我們了解臨床和商業差異化的潛力，對吧？所以說可能早，也可能晚。再說一次，我們必須——我們必須有正確的信念，相信我們正在研究的東西以及潛在的合作或收購能夠真正為患者帶來改變，因為，[cabo-len]，這就是我們能夠在這個競爭非常激烈的市場中創造價值的唯一方法。

In terms of R&D Day and time lines, getting into weeds there probably isn't advisable right now. I know we handle all that in December. I think it will be a great morning, and looking forward to having everybody there. So again, we can frame the science with the strategy, with the details to help everybody see where we're going and how we're going to be able to get these really large aspirational goals to help patients with cancer.

就研發日和時間表而言，目前可能不建議涉足其中。我知道我們會在 12 月處理所有這些事情。我認為這將是一個美好的早晨，並期待著大家的到來。因此，我們可以用策略和細節來建立科學框架，幫助每個人了解我們的目標以及我們將如何實現這些真正宏大的理想目標來幫助癌症患者。

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

Yes. Thank you, and thanks, everybody, for joining us today. Certainly, if you have any follow-up questions, don't hesitate to reach out to me or Varant. We'll get back to you right away.

是的。謝謝你們，也謝謝大家今天加入我們。當然，如果您有任何後續問題，請隨時與我聯繫或 Varant。我們會立即回覆您。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。