Revolution Medicines Inc (RVMD) 2025 Q1 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Revolution Medicines Q1 2025 Earnings Conference Call. (Operator Instructions) Please be advised that today's conference is being recorded.

您好，感謝您的支持。歡迎參加 Revolution Medicines 2025 年第一季財報電話會議。（操作員指示）請注意，今天的會議正在錄音。

I would now like to hand the conference over to your first speaker today, Ryan Asay, Senior Vice President of Corporate Affairs. Please go ahead.

現在，我想將會議交給今天的第一位發言人，企業事務資深副總裁 Ryan Asay。請繼續。

Thank you, and welcome, everyone, to our first quarter 2025 earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicines' Chairman and Chief Executive Officer; Dr. Steve Kelsey, our President of Research and Development; and Dr. Wei Lin, our Chief Medical Officer; and Jack Anders, our Chief Financial Officer.

謝謝大家，歡迎大家參加我們 2025 年第一季財報電話會議。參加今天電話會議的還有 Revolution Medicines 董事長兼首席執行官 Mark Goldsmith 博士；我們的研發總裁 Steve Kelsey 博士；以及我們的首席醫療官魏林博士；以及我們的首席財務官傑克·安德斯 (Jack Anders)。

I would like to inform you that certain statements we make during this call will be forward-looking. Because such statements deal with future events and are subject to many risks and uncertainties, actual results may differ materially from those in the forward-looking statements. For a full discussion of these risks and uncertainties and please review our annual report on Form 10-K and our quarterly reports on Form 10-Q that are filed with the US Securities and Exchange Commission.

我想告訴大家，我們在這次電話會議中所做的某些聲明將具有前瞻性。由於此類陳述涉及未來事件，並受許多風險和不確定性的影響，實際結果可能與前瞻性陳述中的結果有重大差異。有關這些風險和不確定性的全面討論，請查看我們向美國證券交易委員會提交的 10-K 表年度報告和 10-Q 表季度報告。

This afternoon, we released financial results for the quarter ended March 31, 2025, and recent corporate updates. The press release is available on the Investors section of our website at revmed.com. Along with an updated investor presentation, which we will be referencing during today’s call.

今天下午，我們發布了截至 2025 年 3 月 31 日的季度財務表現和最新的公司更新。新聞稿可在我們網站 revmed.com 的投資者部分查閱。附有更新的投資者介紹，我們將在今天的電話會議中參考。

With that, I'll turn the call over to Dr. Mark Goldsmith, Revolution Medicines' Chairman and Chief Executive Officer. Mark?

說完這些，我將把電話轉給 Revolution Medicines 董事長兼執行長馬克‧戈德史密斯博士。標記？

Thanks, Ryan. It's good to be with you this afternoon. Today, I'll highlight some of the progress we've made this quarter against the strategic priorities we outlined earlier this year. I'll then pass the call over to Dr. Steve Kelsey, who will walk through a strategic framework for our developing plans in non-small cell lung cancer. Dr. Wei Lin will then highlight updated data from several of our ongoing non-small cell lung cancer cohorts that provide support for our plans in lung cancer. Jack Anders will then provide a summary of our first quarter financial results before I share closing remarks and open the call to Q&A.

謝謝，瑞安。很高興今天下午能和你在一起。今天，我將重點介紹我們本季根據今年稍早概述的策略重點所取得的一些進展。然後，我將把電話轉給史蒂夫·凱爾西博士，他將介紹我們針對非小細胞肺癌制定計劃的戰略框架。隨後，魏林博士將重點介紹我們正在進行的幾項非小細胞肺癌研究隊列的最新數據，這些數據為我們的肺癌計劃提供了支持。隨後，傑克·安德斯 (Jack Anders) 將對我們第一季的財務業績進行總結，然後我會發表結束語並開始問答環節。

At Revolution Medicines, we remain committed to revolutionizing treatment for patients with RAS-addicted cancers through the discovery, development and delivery of innovative targeted medicines. We continue to make important strides in pursuit of this mission as we execute, advance and extend our understanding of our novel RAS(ON)inhibitors. We believe and have increasingly been able to demonstrate that our compounds have the potential to become important therapeutic options for patients living with RAS-addicted cancers.

在 Revolution Medicines，我們始終致力於透過發現、開發和提供創新的標靶藥物來徹底改變 RAS 成癮癌症患者的治療方法。隨著我們執行、推進和擴展對新型 RAS(ON) 抑制劑的理解，我們在追求這項使命的過程中繼續取得重要進展。我們相信並且已經越來越能夠證明我們的化合物有可能成為 RAS 成癮癌症患者的重要治療選擇。

Our first three clinical stage RAS(ON) inhibitors with highly differentiated and promising clinical profiles include daraxonrasib, a groundbreaking RAS(ON) multi-selective inhibitor, elironrasib, a distinguished G12C selective covalent inhibitor and zoldonrasib, a highly innovative G12D selective covalent inhibitor. We continue to make substantial progress advancing these programs with a vision to maximize the clinical impact across tumor types and lines of therapy through a mix of single agent and combination strategies.

我們首批進入臨床階段的三種具有高度差異化和良好臨床前景的 RAS(ON) 抑制劑包括：突破性的 RAS(ON) 多選擇性抑制劑 daraxonrasib、卓越的 G12C 選擇性共價抑制劑 elironrasib 以及高度創新的 G12D 選擇性共價抑制劑 zoldonrasib。我們繼續在推動這些計畫方面取得實質進展，旨在透過單一藥物和聯合策略最大限度地發揮對不同腫瘤類型和治療方法的臨床影響。

Pancreatic cancer is an important priority, and our strategy involves executing on the ongoing Phase 3 RASolute 302 trial of daraxonrasib in patients with previously treated disease, while moving aggressively into earlier lines of therapy. We're working quickly to prepare for the initiation of two additional Phase 3 studies with daraxonrasib in pancreatic cancer in the second half of 2025.

胰臟癌是我們的首要任務，我們的策略包括對已接受過治療的患者進行正在進行的 3 期 RASolute 302 達拉松拉西布試驗，同時積極進入早期治療階段。我們正在加緊準備，於 2025 年下半年啟動另外兩項 Daraxonrasib 治療胰臟癌的 3 期研究。

One of these trials will be in patients with first-line metastatic disease and is expected to compare a reference arm of patients treated with chemotherapy to two investigational arms, one with patients treated with daraxonrasib monotherapy and one with patients treated with daraxonrasib plus chemotherapy.

其中一項試驗將針對患有第一線轉移性疾病的患者進行，預計將接受化療治療的參考組患者與兩個研究組進行比較，其中一個研究組患者接受 Daraxonrasib 單藥治療，另一個研究組患者接受 Daraxonrasib 加化療治療。

The other early line trial will be as adjuvant treatment for patients with resectable pancreatic cancer, who have undergone surgery and perioperative therapy, typically including chemotherapy.

另一項早期試驗將作為可切除胰臟癌患者的輔助治療，這些患者已經接受過手術和圍手術期治療，通常包括化療。

In addition to this robust plan for daraxonrasib to play an important role in the treatment of pancreatic cancer across lines of therapy, we have similar ambitions for broad development in RAS mutant non-small cell lung cancer.

除了這個強有力的計劃，使達拉松拉西佈在跨療法治療胰腺癌方面發揮重要作用之外，我們還對 RAS 突變型非小細胞肺癌的廣泛發展有著類似的雄心。

The principal focus of today's call is to provide further color and support for our non-small cell lung cancer strategy, and I'd like to invite Dr. Steve Kelsey to walk you through our current conceptual framework. Steve?

今天電話會議的主要重點是為我們的非小細胞肺癌策略提供進一步的色彩和支持，我想邀請史蒂夫凱爾西博士向你們介紹我們目前的概念框架。史蒂夫？

Thanks, Mark. Improving treatment options for patients with RAS mutant lung cancer is an important priority for Revolution medicines. The majority of patients with non-small cell lung cancer are either diagnosed with or later develop metastatic disease. Treatment objectives for these patients include symptom improvement by reducing tumor burden, delaying disease progression, prolonging survival and improving quality of life.

謝謝，馬克。改善 RAS 突變肺癌患者的治療選擇是 Revolution 藥物的重要任務。大多數非小細胞肺癌患者要麼被診斷患有轉移性疾病，要麼後來發展為轉移性疾病。這些患者的治療目標包括透過減少腫瘤負擔來改善症狀、延緩病情進展、延長存活期和提高生活品質。

Thirty percent of patients with non-small cell lung cancer harbor a RAS mutation. There are still no full regulatory approvals for RAS inhibitors in any RAS mutant lung cancer. Nevertheless, due to the commercial availability of KRAS G12C(OFF) inhibitors by accelerated and conditional approval mechanisms, RAS mutant non-small cell lung cancer has effectively evolved into two diseases and treatment paradigms.

30% 的非小細胞肺癌患者帶有 RAS 突變。目前，RAS 抑制劑治療任何 RAS 突變型肺癌尚未獲得監管部門的全面批准。儘管如此，由於 KRAS G12C(OFF) 抑制劑透過加速和有條件審批機制實現商業化，RAS 突變型非小細胞肺癌實際上已演變為兩種疾病和治療範例。

G12C mutant disease, which represents around 12% of non-small cell lung cancer and other RAS mutant non-small cell lung cancer, which we are referring to as non-G12C RAS mutant non-small cell lung cancer.

G12C 突變疾病，約佔非小細胞肺癌的 12% 和其他 RAS 突變非小細胞肺癌，我們稱之為非 G12C RAS 突變非小細胞肺癌。

The second group counts for around 18% of non-small cell lung cancer. We expect segmentation of the RAS mutant non-small cell lung cancer space to continue into mutational groups as other mutant selective inhibitors advance through clinical development and receive regulatory approvals.

第二類約佔非小細胞肺癌的18%。我們預計，隨著其他突變選擇性抑制劑在臨床開發中取得進展並獲得監管部門的批准，RAS 突變非小細胞肺癌空間將繼續細分為突變組。

Our aim at Revolution Medicines is to establish our portfolio of RAS(ON) inhibitors as the leading therapies for patients with RAS mutant non-small cell lung cancer across all RAS mutations and lines of therapy. We strive to develop first and or best-in-class RAS(ON) inhibitors and combinations.

Revolution Medicines 的目標是將我們的 RAS(ON) 抑制劑產品組合打造為針對所有 RAS 突變和治療方法的 RAS 突變型非小細胞肺癌患者的領先療法。我們致力於開發一流的或最佳的 RAS(ON) 抑制劑和組合。

Our strategy for metastatic disease depends on a number of variables. First, which RAS mutation the tumor harbors and whether a mutant selective RAS(ON) inhibitor has achieved proof of concept. Second, the line of therapy for metastatic disease as the expectations and standards of care are different between initial therapy and salvage therapy.

我們針對轉移性疾病的策略取決於許多變數。首先，腫瘤存在哪一種 RAS 突變，以及突變選擇性 RAS(ON) 抑制劑是否已獲得概念驗證。其次，轉移性疾病的治療方法不同，因為初始治療和挽救治療的預期和護理標準不同。

Daraxonrasib has shown encouraging anti-tumor activity in patients with tumors harboring a wide range of RAS mutations. Nonetheless, in the face of RAS-addiction by such tumors, we expect that mutant selective inhibitors should also have a role in treating tumors with corresponding RAS driver mutations.

Daraxonrasib 在患有多種 RAS 突變的腫瘤患者中表現出令人鼓舞的抗腫瘤活性。儘管如此，面對此類腫瘤的 RAS 成癮，我們預期突變選擇性抑制劑也應該在治療具有相應 RAS 驅動突變的腫瘤中發揮作用。

Combining these mutant selective inhibitors with a RAS(ON) multi selective inhibitor may play an important role by delivering deeper target inhibition and overcoming resistance mechanisms in a way that neither approach can achieve on its own.

將這些突變選擇性抑制劑與 RAS(ON) 多選擇性抑制劑結合，可以發揮重要作用，提供更深層的標靶抑制並克服抗性機制，而這兩種方法單獨使用時都無法實現這一點。

Our previously published data show that daraxonrasib is active against a broad range of RAS mutations that have been frequently identified as mechanisms of escape from mutant selective KRAS inhibitors. Consistent with this and as we recently presented at AACR, new RAS point mutations are an infrequent cause of escape from daraxonrasib in pancreatic cancer. A RAS(ON) inhibitor doublet combination has the goal of improving outcomes and potentially providing a chemotherapy sparing option for patients with RAS mutant non-small cell lung cancer.

我們先前發表的數據表明，daraxonrasib 對多種 RAS 突變具有活性，這些突變經常被認為是逃避突變選擇性 KRAS 抑制劑的機制。與此一致，正如我們最近在 AACR 上所介紹的那樣，新的 RAS 點突變是胰臟癌逃避 daraxonrasib 治療的一個罕見原因。RAS(ON) 抑制劑雙聯療法的目標是改善療效，並可能為 RAS 突變型非小細胞肺癌患者提供化療節省選擇。

In the previously treated metastatic setting, use of a single agent RAS inhibitor may be sufficient to improve outcomes over the current chemotherapy standard of care. This is the approach we're taking with daraxonrasib in patients with previously treated Ras mutant non-small cell lung cancer in the RASolve 301 study.

在先前治療過的轉移性環境中，使用單一藥物 RAS 抑制劑可能足以改善目前化療標準的治療效果。這是我們在 RASolve 301 研究中對接受過治療的 Ras 突變型非小細胞肺癌患者使用 daraxonrasib 的方法。

For first-line treatment of metastatic disease, the dominant standard of care includes immune checkpoint inhibitors, primarily pembrolizumab. Demonstrating safety and tolerability with pembrolizumab is critical as a means of enabling first-line therapy and maximizing the durability of any clinical benefit.

對於轉移性疾病的第一線治療，主要的標準治療方法包括免疫檢查點抑制劑，主要是派姆單抗。證明 pembrolizumab 的安全性和耐受性對於實現一線治療和最大限度延長臨床益處的持久性至關重要。

These concepts have currently been reduced to practice by Revolution Medicines. Single agent daraxonrasib provides a foundation for the investigation of RAS(ON) inhibitors in all RAS mutant non-small cell lung cancer in the second-line and beyond setting. As recently presented at AACR, zoldonrasib has encouraging activity as a single agent in second-line plus RAS G12D mutant non-small cell lung cancer.

這些概念目前已被 Revolution Medicines 付諸實行。單一藥物 daraxonrasib 為二線及以後治療中所有 RAS 突變型非小細胞肺癌的 RAS(ON) 抑制劑的研究奠定了基礎。正如最近在 AACR 上所介紹的那樣，zoldonrasib 作為二線加 RAS G12D 突變非小細胞肺癌的單一藥物具有令人鼓舞的活性。

In the first-line, RAS G12C non-small cell lung cancer setting, we aspire to develop chemotherapy sparing RAS(ON) inhibitor doublet of daraxonrasib plus elironrasib with pembrolizumab and thereby reserve platinum-based chemotherapy for second-line treatment. Doing so has the potential to contribute to an improvement in overall survival.

在一線 RAS G12C 非小細胞肺癌治療中，我們渴望開發保留化療的 RAS(ON) 抑制劑雙聯體，即 daraxonrasib 加 elironrasib 與 pembrolizumab，從而將鉑類化療保留用於二線治療。這樣做有可能有助於提高整體存活率。

In first-line RAS non-G12C non-small cell lung cancer, we plan to develop daraxonrasib in combination with standard of care. Eventually, zoldonrasib with its encouraging monotherapy profile may offer a path to another chemotherapy sparing RAS(ON) inhibitor doublet for patients with RAS G12D tumors. And similar doublet approaches may be possible with other RAS mutant selective inhibitors such as RMC-5127 targeting RAS G12V.

在一線 RAS 非 G12C 非小細胞肺癌中，我們計劃開發 daraxonrasib 與標準治療相結合。最終，zoldonrasib 憑藉其令人鼓舞的單一療法特性可能為 RAS G12D 腫瘤患者提供另一種節省化療的 RAS(ON) 抑制劑雙藥療法的途徑。其他 RAS 突變體選擇性抑制劑（如針對 RAS G12V 的 RMC-5127）也可能採用類似的雙聯方法。

I will now turn the call over to Dr. Wei Lin to provide an update across our non-small cell lung cancer clinical programs. Wei?

現在我將把電話轉給魏林博士，讓他介紹我們的非小細胞肺癌臨床計畫的最新進展。魏？

Thank you, Steve. I'll start by providing monotherapy updates across our portfolio. Beginning with daraxonrasib, our most advanced RAS(ON) inhibitor. This multi selective inhibitor has demonstrated compelling results across multiple tumors, including lung cancer, and is currently being evaluated in a Phase 3 registrational study for patients with previously treated non-small cell lung cancer.

謝謝你，史蒂夫。我將首先提供我們產品組合中單一療法的最新情況。從我們最先進的 RAS(ON) 抑制劑 daraxonrasib 開始。這種多選擇性抑制劑已在包括肺癌在內的多種腫瘤中顯示出令人信服的效果，目前正在針對先前接受過治療的非小細胞肺癌患者進行 3 期註冊研究評估。

We're currently activating study sites for RASolve 301. The study randomized approximately four twenty patients to either daraxonrasib monotherapy or docetaxel. These patients must have received either one or two prior lines of therapy, including immunotherapy and platinum-based chemotherapy given either concurrently or sequentially. RASolve 301 incorporates a nested design with a primary analysis being performed in the core population of non-small cell lung cancer patients with RAS G12X mutations, excluding G12C. Extended population will incorporate all patients with RAS mutant non-small cell lung cancer, including those with tumors harboring G12C, G13 or Q61 mutations. The study has dual primary endpoints of progression free survival and overall survival.

我們目前正在啟動 RASolve 301 的學習網站。研究將大約四十二名患者隨機分配接受達拉松拉西布單藥治療或多西他賽治療。這些患者必須接受一到兩種先前的治療，包括同時或連續進行的免疫療法和鉑類化療。RASolve 301 採用嵌套設計，對攜帶 RAS G12X 突變（不包括 G12C）的非小細胞肺癌患者核心族群進行主要分析。擴展族群將涵蓋所有 RAS 突變型非小細胞肺癌的患者，包括腫瘤含有 G12C、G13 或 Q61 突變的患者。研究有兩個主要終點：無惡化存活期和總存活期。

Moving to G12D non-small cell lung cancer. We've previously shown promising activity by daraxonrasib in patients with these tumors and the ongoing RASolve 301 recreational study includes such patients.

轉向 G12D 非小細胞肺癌。我們先前已證明 daraxonrasib 對患有這些腫瘤的患者有良好的療效，正在進行的 RASolve 301 娛樂研究也包括此類患者。

Last month at AACR, initial clinical results were presented for zoldonrasib, our RAS(ON) G12D-Selective Covalent Inhibitor from a non-small cell lung cancer cohort. I'll walk you through these data.

上個月在 AACR 上，我們展示了 zoldonrasib（我們的 RAS(ON) G12D 選擇性共價抑制劑）針對非小細胞肺癌患者的初步臨床結果。我將帶您了解這些數據。

Zoldonrasib was well tolerated with manageable and predominantly low-grade treatment related adverse events as shown on the safety table. As of the December 02, 2024, data cutoff, at the 1200 mg once daily dose, two Grade 3 adverse events were reported among ninety patients with only two dose interruptions and no dose reductions. Zoldonrasib achieved a favorable mean dose intensity of 98%.

如安全表所示，Zoldonrasib 耐受性良好，治療相關不良事件可控制且主要為低度不良事件。截至 2024 年 12 月 2 日數據截止，以 1200 毫克每日一次的劑量服用，90 名患者中報告了兩起 3 級不良事件，僅有兩次劑量中斷，沒有劑量減少。Zoldonrasib 達到了 98% 的良好平均劑量強度。

Zoldonrasib monotherapy at the 1200 mg daily dose demonstrated encouraging antitumor activity. The waterfall plot shows the best percentage change in tumor size for patients with non-small cell lung cancer who received their first dose of zoldonrasib at least eight weeks prior to the data cutoff date. The objective response rate was 61%, including patients with a confirmed response or a response that was pending confirmation. The disease control rate was 89%. We'll continue following these patients to define durability.

每日劑量 1200 毫克的 Zoldonrasib 單一療法表現出令人鼓舞的抗腫瘤活性。瀑布圖顯示了在數據截止日期前至少八週接受第一劑 zoldonrasib 治療的非小細胞肺癌患者的腫瘤大小最佳百分比變化。客觀緩解率為 61%，包括已確認緩解或有待確認緩解的患者。疾病控制率為89%。我們將繼續追蹤這些患者以確定其耐久性。

Now I'll move to our RAS(ON) G12C mutant selective covalent inhibitor, elironrasib, in non-small cell lung cancer. We reported the first clinical data on elironrasib in non-small cell lung cancer at the Triple meeting in 2023. And today, I'll share updated elironrasib monotherapy data that includes more patients and longer follow-up as a foundation for combination strategies to move into first-line metastatic and eventually earlier lines of non-small cell lung cancer.

現在我將介紹我們的 RAS(ON) G12C 突變選擇性共價抑制劑 elironrasib 在非小細胞肺癌中的應用。我們在 2023 年的三重會議上報告了 elironrasib 治療非小細胞肺癌的首批臨床數據。今天，我將分享更新的 elironrasib 單藥治療數據，其中包括更多患者和更長時間的隨訪，作為聯合治療策略的基礎，以進入非小細胞肺癌的一線轉移性和最終的早期治療。

As of the April 07, 2025, data cutoff, 36 patients who had received prior treatment with standard care were treated with elironrasib monotherapy at 200 mg twice daily. Elironrasib was generally well tolerated with treatment related adverse events consistent with previously reported data. The most frequently observed treatment-related adverse events were gastrointestinal and asymptomatic QTc prolongation. Elironrasib achieved a favorable mean dose intensity of 94%.

截至 2025 年 4 月 7 日數據截止，36 名曾接受標準治療的患者接受 elironrasib 單藥治療，每日兩次，每次 200 毫克。Elironrasib 整體耐受性良好，治療相關不良事件與先前報告的數據一致。最常見的治療相關不良事件是胃腸道和無症狀 QTc 延長。Elironrasib 達到了 94% 的良好平均劑量強度。

Here, we show the clinical activity in the same 36 patients treated with elironrasib monotherapy, the dose of 200 mg twice daily. The objective response rate in these patients was 56%. The disease control rate was 94%. The estimated median progression-free survival in these patients was 9.9 months.

在這裡，我們展示了同樣的 36 名接受 elironrasib 單一療法治療的患者的臨床活性，劑量為每天兩次 200 毫克。這些患者的客觀緩解率為56%。疾病控制率為94%。這些患者的預期中位無惡化存活期為 9.9 個月。

I'll now cover our combination of clinical development to enable our goal of improving treatment outcomes for patients with RAS mutant non-small cell lung cancer in the first-line metastatic setting.

我現在將介紹我們的臨床開發組合，以實現我們的目標，即改善一線轉移性 RAS 突變型非小細胞肺癌患者的治療結果。

The need for improved treatment options for patients with metastatic non-small cell lung cancer remains high. In the first-line setting, two regimens are widely used globally. Pembrolizumab plus chemotherapy is the most commonly used treatment for all patients regardless of their tumor PD-L1 expression status as measured by Tumor Proportion Score or TPS. And pembrolizumab monotherapy is the preferred regimen in patients with TPS greater than or equal to 50%, which accounts for about 1/3 of patients with non-small cell lung cancer.

轉移性非小細胞肺癌患者仍需要改進治療方案。在第一線治療中，全球廣泛使用兩種方案。無論腫瘤 PD-L1 表現狀態（以腫瘤比例評分或 TPS 衡量）如何，Pembrolizumab 合併化療都是所有患者最常用的治療方法。而對於TPS大於或等於50%的患者，pembrolizumab單藥治療是首選方案，這一人群約佔非小細胞肺癌患者的1/3。

While the introduction of immunotherapy has been transformative for patients with non-small cell lung cancer, especially those with high PD-L1 expression. As the data in this table indicate, non-small cell lung cancer remains a disease with high unmet need. Because among the approximately 2/3 of patients who have tumors with lower or no PD-L1 expression, even the best available standard care has not resulted in reported response rates above 40%.

而免疫療法的引進對於非小細胞肺癌患者，尤其是PD-L1表達高的患者來說，具有變革性的意義。如該表中的數據所示，非小細胞肺癌仍然是一種尚未滿足的疾病。因為在約 2/3 的 PD-L1 表達較低或無 PD-L1 表達的腫瘤患者中，即使是最好的標準治療也無法使報告的反應率達到 40% 以上。

In RAS mutant non-small cell lung cancer in the second-line and beyond, treatment is generally either the chemotherapy docetaxel or a KRAS G12C(OFF) inhibitor. As illustrated in the table, reported response rates for docetaxel have been less than 15%, even with the commercially available KRAS G12C(OFF) inhibitors of sotorasib and adagrasib. Reported patient outcomes have been modest with response rates of approximately 30%.

對於二線以上RAS突變型非小細胞肺癌，治療通常採用化療多西他賽或KRAS G12C(OFF)抑制劑。如表所示，即使使用市售的 KRAS G12C(OFF) 抑制劑 sotorasib 和 adagrasib，報告的多西他賽的反應率也低於 15%。報告的患者治療效果一般，緩解率約 30%。

Combinations are likely to remain a foundation of first-line metastatic treatment for non-small cell lung cancer. And our main objective is to determine the best way to bring targeted RAS inhibitors into combination with immunotherapy for the first-line treatment of RAS mutant non-small cell lung cancer. These figures from preclinical experiments illustrate two concepts that guide our clinical approaches.

聯合治療可能仍將是非小細胞肺癌一線轉移性治療的基礎。我們的主要目標是確定將標靶 RAS 抑制劑與免疫療法結合作為 RAS 突變非小細胞肺癌一線治療的最佳方法。這些來自臨床前實驗的數據說明了指導我們臨床方法的兩個概念。

The first concept shown on the left is that two RAS(ON) inhibitors can be combined to increase anti-tumor activity. In this experiment with a KRAS G12C non-small cell lung cancer model, either elironrasib or daraxonrasib alone significantly increased progression-free survival compared to control as measured by time to tumor doubling. Notably, the combination of elironrasib plus daraxonrasib prolong progression free survival even further, indicating additive durability from the RAS(ON) inhibitor doublet.

左側顯示的第一個概念是可以組合兩種 RAS(ON) 抑制劑來增加抗腫瘤活性。在這項使用 KRAS G12C 非小細胞肺癌模型的實驗中，以腫瘤倍增時間來衡量，單獨使用 elironrasib 或 daraxonrasib 與對照組相比，無惡化存活期顯著增加。值得注意的是，elironrasib 和 daraxonrasib 的組合可以進一步延長無惡化存活期，顯示 RAS(ON) 抑制劑雙聯劑具有附加耐久性。

The second concept shown in the experiment on the right is that this RAS(ON) inhibitor doublet significantly synergizes with immunotherapy. In this experiment, we used a refractory KRAS G12C non-small cell lung cancer tumor that was unresponsive to anti PD-1 inhibitor alone and only partially responsive to anti PD-1 combined with either RAS(ON) inhibitor. Essentially, no progression was seen in this model during 100 days of treatment with anti PD-1 combined with the RAS(ON) inhibitor doublet.

右側實驗展示的第二個概念是，這種 RAS(ON) 抑制劑雙聯體與免疫療法有顯著的協同作用。在本實驗中，我們使用了一種難治性 KRAS G12C 非小細胞肺癌腫瘤，該腫瘤對單獨的抗 PD-1 抑制劑無反應，而對抗 PD-1 與 RAS(ON) 抑制劑的組合僅有部分反應。基本上，在使用抗 PD-1 和 RAS(ON) 抑制劑雙聯療法治療該模型 100 天期間沒有觀察到任何進展。

Encouraged by preclinical results of this sort, I will now describe new clinical data from our evaluation of pairwise combinations of daraxonrasib plus pembrolizumab, elironrasib plus pembrolizumab and elironrasib plus daraxonrasib that suggest these concepts may translate in patients with KRAS G12C non-small cell lung cancer.

受到此類臨床前結果的鼓舞，我現在將描述我們對 daraxonrasib 加 pembrolizumab、elironrasib 加 pembrolizumab 和 elironrasib 加 daraxonrasib 的配對組合評估的新臨床數據，這些數據表明這些概念可能適用於 KRAS G12C 非小細胞肺癌患者。

The first combination data set I'll review is daraxonrasib plus pembrolizumab with or without chemotherapy. Daraxonrasib plus pembrolizumab with or without chemotherapy has been generally well tolerated in patients with non-small cell lung cancer. Previously, we showed acceptable tolerability for the combination of daraxonrasib with pembrolizumab in later line patients. And with further follow-up, the tolerability profile in those patients has remained stable. Today, we're focusing on patients with first-line disease.

我將要審查的第一個組合資料集是 daraxonrasib 加 pembrolizumab，聯合或不聯合化療。Daraxonrasib 合併 pembrolizumab 治療（無論是否合併化療）對非小細胞肺癌患者通常具有良好的耐受性。先前，我們證明了 daraxonrasib 與 pembrolizumab 聯合治療在後期患者中具有可接受的耐受性。經過進一步的跟踪，這些患者的耐受性狀況保持穩定。今天，我們關注的是患有第一線疾病的患者。

While the follow-up is shorter for patients in the first-line setting, the tolerability profile of daraxonrasib plus pembrolizumab is consistent with what has been observed in the second-line setting with or without the addition of chemotherapy. No new safety signals were seen, and the overall tolerability profile is consistent with that of daraxonrasib plus standard care agents. Rash, gastrointestinal toxicities and stomatitis mucositis remain the most commonly observed adverse events for daraxonrasib, and neutropenia and thrombocytopenia emerged with addition of chemotherapy.

雖然第一線治療患者的追蹤時間較短，但達拉松拉西布加派姆單抗的耐受性概況與二線治療中觀察到的一致，無論是否添加化療。沒有發現新的安全訊號，整體耐受性概況與 daraxonrasib 加標準護理藥物一致。皮疹、胃腸道毒性和口腔黏膜炎仍然是達拉松拉西布最常見的不良事件，而隨著化療的加入，嗜中性白血球減少症和血小板減少症出現。

The tolerability profile supports the further development of daraxonrasib plus pembrolizumab with or without chemotherapy. Dose reductions and discontinuations of daraxonrasib or pembrolizumab in this combination were modest. Daraxonrasib achieved a favorable mean dose intensity of 93% in combination with pembrolizumab and 90% with additional chemotherapy. Only a limited number of first-line patients have had sufficient follow-up to have had a tumor assessment, we're encouraged by the antitumor activity seen to date.

耐受性概況支持進一步開發 daraxonrasib 加 pembrolizumab 聯合或不聯合化療。在此組合中，daraxonrasib 或 pembrolizumab 的劑量減少和停藥幅度不大。Daraxonrasib 與 pembrolizumab 聯合使用時達到了 93% 的良好平均劑量強度，與附加化療聯合使用時達到了 90% 的良好平均劑量強度。只有有限數量的一線患者進行了足夠的隨訪以進行腫瘤評估，我們對迄今為止看到的抗腫瘤活性感到鼓舞。

In the left figure, patients had tumors with TPS greater than or equal to 50% and were treated with daraxonrasib plus pembrolizumab, consistent with the population who would have received pembrolizumab monotherapy of standard care. Of these seven efficacy valuable patients who had undergone at least one tumor assessment, 86% of these TPS greater than or equal to 50% patients had a RECIST response and all had achieved disease control and remained on treatment. While the data set will continue to evolve with addition of more patients and longer follow-up, this is a very encouraging start.

在左圖中，患者的腫瘤 TPS 大於或等於 50%，並接受了 daraxonrasib 加 pembrolizumab 治療，這與接受標準治療的 pembrolizumab 單藥治療的人一致。這7例有療效價值且至少接受過一次腫瘤評估的患者中，86%（TPS≥50%）的患者獲得了RECIST反應，且所有患者均已達到病情控制並繼續接受治療。雖然隨著更多患者的加入和更長的隨訪，數據集將繼續發展，但這是一個非常令人鼓舞的開始。

In the figure on the right, patients with TPS less than 50% were treated with daraxonrasib plus pembrolizumab and chemotherapy, consistent with the roughly 2/3 of first-line patients who would likely receive pembrolizumab plus chemotherapy of standard care. Of the 10 efficacy valuable patients who had undergone at least one scan, 60% of these TPS less than 50% patients had a RECIST response and 90% achieved disease control. These data support the continued development of daraxonrasib plus standard care in first-line RAS mutant non-small cell lung cancer.

在右圖中，TPS 低於 50% 的患者接受了 daraxonrasib 加 pembrolizumab 和化療的治療，這與大約 2/3 的一線患者可能接受 pembrolizumab 加標準治療的化療的情況一致。在接受過至少一次掃描的 10 名有療效價值的患者中，60% 的患者獲得了 RECIST 反應，90% 的患者獲得了疾病控制。這些數據支持在 RAS 突變型非小細胞肺癌一線治療中繼續開發 daraxonrasib 聯合標準治療。

I'll now touch on the elironrasib plus pembrolizumab combination. Demonstrating the safety of this combination is important as we take a pairwise approach toward our goal of developing a chemotherapy sparing triplet combination of elironrasib, daraxonrasib and pembrolizumab in patients with first-line metastatic KRAS G12C non-small cell lung cancer.

現在我將談談 elironrasib 和 pembrolizumab 的組合。證明這種組合的安全性非常重要，因為我們採用成對方法來實現我們的目標，即為一線轉移性 KRAS G12C 非小細胞肺癌患者開發一種節省化療的三聯組合，即 elironrasib、daraxonrasib 和 pembrolizumab。

We previously showed acceptable tolerability for the elironrasib plus pembrolizumab combination in the second-line plus setting. With further follow-up of few of those patients, we have not observed an increase in additive toxicity. Today, we'll focus on initial results in patients with first-line non-small cell lung cancer.

我們先前證明，在二線治療中，elironrasib 加 pembrolizumab 組合具有可接受的耐受性。透過對其中幾例患者進行進一步跟踪，我們並未觀察到添加劑毒性的增加。今天，我們將重點放在第一線非小細胞肺癌患者的初步結果。

As of the February 10, 2025, data cutoff, the combination of elironrasib with pembrolizumab showed a well-tolerated profile with few Grade 3 or higher treatment related adverse events. No new safety signals were observed. This tolerability profile translated to an acceptable dose modification rate in either the second-line or first-line setting. And elironrasib maintained a favorable mean dose intensity of 85%.

截至 2025 年 2 月 10 日的數據截止，elironrasib 與 pembrolizumab 的組合顯示出良好的耐受性，並且 3 級或更高級別治療相關不良事件很少。沒有觀察到新的安全訊號。這種耐受性特徵轉化為二線或第一線治療中可接受的劑量調整率。並且 elironrasib 維持了 85% 的良好平均劑量強度。

The combination of elironrasib with pembrolizumab showed encouraging preliminary antitumor activity. Among five efficacy valuable patients with first-line non-small cell lung cancer and a TPS greater than or equal to 50%, all achieved a RECIST response.

elironrasib 與 pembrolizumab 的組合顯示出令人鼓舞的初步抗腫瘤活性。在 5 名有療效價值的一線非小細胞肺癌患者中，TPS 大於或等於 50%，所有患者均獲得了 RECIST 反應。

Our development strategy in the first-line RAS G12C mutant non-small cell lung cancer is to replace the standard care with the triplet regimen of elironrasib, daraxonrasib and pembrolizumab as a chemo sparing regimen. I've just shown data supporting the combinability and anti-tumor activity of daraxonrasib plus pembrolizumab and elironrasib plus pembrolizumab.

我們在一線 RAS G12C 突變型非小細胞肺癌方面的開發策略是用 elironrasib、daraxonrasib 和 pembrolizumab 的三聯方案作為化療節約方案取代標準治療。我剛剛展示了支持 daraxonrasib 加 pembrolizumab 和 elironrasib 加 pembrolizumab 的可組合性和抗腫瘤活性的數據。

The third pairwise combination needed to support this triplet regimen is the RAS(ON) inhibitor doublet of elironrasib plus daraxonrasib. This RAS(ON) inhibitor doublet concept is supported by strong results in preclinical models, including models that refractory to monotherapy approaches. In these preclinical models, deep and durable responses are seen in RAS(ON) inhibitor doublets.

支持此三聯療法所需的第三對組合是 RAS(ON) 抑制劑雙聯劑 elironrasib 加 daraxonrasib。RAS(ON) 抑制劑雙聯體概念得到了臨床前模型（包括對單一療法有抵抗力的模型）的有力支持。在這些臨床前模型中，RAS(ON) 抑制劑雙聯體表現出深度和持久的反應。

In December 2024, we shared initial clinical data for the RAS(ON) inhibitor doublet of elironrasib plus daraxonrasib to establish the mechanistic proof of principle for this combination. We evaluated a challenging population of colorectal cancer patients who had been previously treated with not only standard care chemotherapy, but also with KRAS G12C(OFF) inhibitors and anti-EGFR antibodies. These early results demonstrated an acceptable tolerability profile along with encouraging antitumor activity in a very difficult to treat patient population. These results provided strong rationale for continued development of this RAS(ON) inhibitor doublet approach across tumor types and lines of therapy.

2024 年 12 月，我們分享了 RAS(ON) 抑制劑雙聯藥 elironrasib 加 daraxonrasib 的初步臨床數據，以建立該組合的機制原理證明。我們評估了一組具有挑戰性的大腸直腸癌患者，這些患者之前不僅接受過標準化療，還接受過 KRAS G12C(OFF) 抑制劑和抗 EGFR 抗體治療。這些早期結果證明了可接受的耐受性以及在極難治療的患者群體中令人鼓舞的抗腫瘤活性。這些結果為在各種腫瘤類型和治療方法中繼續開發這種 RAS(ON) 抑制劑雙聯方法提供了強有力的理論基礎。

Today, I'll share initial dose finding data from this RAS(ON) inhibitor doublet in patients with non-small cell lung cancer. The data in this table demonstrate the combinability of elironrasib with daraxonrasib with a tolerability profile that is largely consistent with that of daraxonrasib itself. Even with longer follow-up, hepatotoxicity did not emerge as a safety signal in this larger cohort of lung cancer patients.

今天，我將分享這種 RAS(ON) 抑制劑雙聯劑在非小細胞肺癌患者中的初始劑量探索數據。此表中的數據證明了 elironrasib 與 daraxonrasib 的可組合性，其耐受性特徵與 daraxonrasib 本身基本一致。即使經過更長時間的隨訪，肝毒性並沒有成為這一較大肺癌患者群體的安全信號。

QT prolongation of ECG was not symptomatic and is not common with a Grade 3 rate of only 3%. This tolerability profile translated to no treatment discontinuations and a favorable mean dose intensity of 95% for elironrasib and 85% for daraxonrasib. The combination of elironrasib plus daraxonrasib showed encouraging preliminary antitumor activity in 26 patients with previously treated KRAS G12C non-small cell lung cancer, who had been previously treated with a KRAS G12C(OFF) inhibitor. Because dose optimization of the RAS(ON) inhibitor doublet is ongoing, we're sharing daraxonrasib at doses ranging from 100 mg to 200 mg.

心電圖 QT 延長沒有症狀，並不常見，3 級發生率僅 3%。這種耐受性特徵意味著無需停止治療，且 elironrasib 的平均劑量強度為 95%，daraxonrasib 的平均劑量強度為 85%。elironrasib 和 daraxonrasib 的組合在 26 名先前接受過治療的 KRAS G12C 非小細胞肺癌患者中顯示出令人鼓舞的初步抗腫瘤活性，這些患者之前曾接受過 KRAS G12C(OFF) 抑制劑治療。由於 RAS(ON) 抑制劑雙聯體的劑量優化正在進行中，我們分享的 daraxonrasib 劑量範圍為 100 毫克至 200 毫克。

On the left, we're showing the elironrasib monotherapy data in patients who were previously treated with a KRAS G12C(OFF) inhibitor. Response rate and disease control rate for elironrasib monotherapy were 42% and 79%, respectively.

左側我們展示了先前接受 KRAS G12C(OFF) 抑制劑治療的患者的 elironrasib 單藥治療數據。Elironrasib 單藥治療的反應率和疾病控制率分別為 42% 和 79%。

On the right, for the combination of elironrasib and daraxonrasib, the response rate was 62% and the disease control rate was 92%, well above the activity seen in this population with elironrasib monotherapy. The majority of patients on the combination remained on treatment of the February 10, 2025, data cutoff date.

右側為 elironrasib 和 daraxonrasib 組合治療，緩解率為 62%，疾病控制率為 92%，遠高於該族群使用 elironrasib 單一藥物治療的療效。大多數接受聯合治療的患者仍在接受截至 2025 年 2 月 10 日數據截止日期的治療。

Taking a step back and looking at our data driven lung cancer strategy, we believe we have a clear path to pursuing our ambition to change the standard care for patients with RAS mutant lung cancer, both in first-line metastatic and in earlier lines of treatment. We launched our initiative in non-small cell lung cancer with our registrational study for daraxonrasib monotherapy in previously treated patients with RAS mutant lung cancer.

回顧我們的數據驅動型肺癌策略，我們相信，我們有一條清晰的道路來實現我們的目標，即改變 RAS 突變型肺癌患者的標準治療，無論是在一線轉移性治療中還是在早期治療中。我們啟動了非小細胞肺癌領域的計劃，對接受過治療的 RAS 突變型肺癌患者進行 Daraxonrasib 單藥治療的註冊研究。

The emerging zoldonrasib data point to clear opportunities to continue evaluating zoldonrasib in patients with RAS G12D mutant non-small cell lung cancer as monotherapy and in combination.

新出現的 zoldonrasib 數據表明，有明確的機會繼續評估 zoldonrasib 作為單一療法和聯合療法對 RAS G12D 突變型非小細胞肺癌患者的作用。

The three pairwise combinations of daraxonrasib plus pembrolizumab, elironrasib plus pembrolizumab and the RAS(ON) inhibitor doublet of elironrasib plus daraxonrasib all acceptable tolerability and encouraging antitumor activity and create options in the first-line treatment setting.

Daraxonrasib 加 pembrolizumab、elironrasib 加 pembrolizumab 以及 RAS(ON) 抑制劑雙聯體 elironrasib 加 daraxonrasib 這三種成對組合均具有可接受的耐受性和令人鼓舞的抗腫瘤活性，並在第一線治療環境中創造了選擇。

For patients with tumors harboring RAS G12C, we plan to pursue a chemotherapy sparing RAS(ON) inhibitor doublet treatment, including the elironrasib plus daraxonrasib along with checkpoint inhibitor. For patients with non-G12C disease, we plan to develop daraxonrasib in combination with standard care chemotherapy along with checkpoint inhibitor.

對於 RAS G12C 腫瘤的患者，我們計劃採用節省化療的 RAS(ON) 抑制劑雙聯治療，包括 elironrasib 加 daraxonrasib 以及檢查點抑制劑。對於非 G12C 疾病患者，我們計劃開發 daraxonrasib 與標準護理化療以及檢查點抑制劑的聯合使用。

We believe each compound in our clinical stage RAS(ON) inhibitor portfolio has the potential to transform treatment for patients living with RAS mutant non-small cell lung cancer.

我們相信，我們臨床階段 RAS(ON) 抑制劑產品組合中的每種化合物都有可能改變 RAS 突變型非小細胞肺癌患者的治療方法。

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

說完這些，我會把電話轉給傑克。

Thanks, Wei. We ended the first quarter of 2025 with $2.1 billion in cash and investments, which we project can fund planned operations into the second half of 2027 based on our current operating plan.

謝謝，魏。截至 2025 年第一季度，我們擁有 21 億美元現金和投資，根據我們目前的營運計劃，我們預計這些資金可以為 2027 年下半年的計劃營運提供資金。

R&D expenses for the first quarter of 2025 were $205.7 million compared to $118 million for the first quarter of 2024. The increase in R&D expenses was primarily due to increases in clinical trial related expenses and manufacturing expenses for our three clinical stage programs, with daraxonrasib being the largest driver of the increase given the program is now in two Phase 3 trials.

2025 年第一季的研發費用為 2.057 億美元，而 2024 年第一季的研發費用為 1.18 億美元。研發費用的增加主要是由於我們三個臨床階段項目的臨床試驗相關費用和製造費用的增加，其中 daraxonrasib 是成長的最大驅動力，因為該計畫目前處於兩個 3 期試驗階段。

Personnel related expenses and stock-based compensation expense also increased in 2025 due to additional headcount. G&A expenses for the first quarter of 2025 were $35 million compared to $22.8 million for the first quarter of 2024. The increase in G&A expenses was primarily due to increases in personnel related expenses and stock-based compensation associated with additional headcount and commercial preparation activities.

由於員工人數增加，2025 年人事相關費用和股票薪酬費用也將增加。2025 年第一季的一般及行政費用為 3,500 萬美元，而 2024 年第一季的一般及行政費用為 2,280 萬美元。一般及行政費用的增加主要是由於與增加員工人數和商業準備活動相關的人事相關費用和股票薪酬的增加。

Net loss for the first quarter of 2025 was $213.4 million compared to $116 million for the first quarter of 2024. The increase in net loss was due to higher operating expenses.

2025 年第一季淨虧損為 2.134 億美元，而 2024 年第一季淨虧損為 1.16 億美元。淨虧損增加是由於營運費用增加。

We are reiterating our 2025 financial guidance and continue to expect projected full year 2025 GAAP net loss to be between $840 million and $900 million which includes estimated non-cash stock-based compensation expense of between $115 million and $130 million.

我們重申 2025 年財務指引，並繼續預計 2025 年全年 GAAP 淨虧損將在 8.4 億美元至 9 億美元之間，其中包括估計 1.15 億美元至 1.3 億美元的非現金股票薪酬費用。

That concludes the financial update. I'll now turn the call back over to Mark.

財務更新到此結束。我現在將電話轉回給馬克。

Thank you, Jack. We are making meaningful progress as we successfully execute on our 2025 strategic priorities in pursuit of our goal to revolutionize treatment for patients with RAS-addicted cancers. A key focus this year is executing on the daraxonrasib registrational studies in both previously treated pancreatic and non-small cell lung cancers.

謝謝你，傑克。我們在成功執行 2025 年策略重點的過程中取得了有意義的進展，以實現徹底改變 RAS 成癮癌症患者治療的目標。今年的一個重點是針對先前治療過的胰腺癌和非小細胞肺癌進行 daraxonrasib 註冊研究。

I'm pleased to share that RASolute 302, our ongoing global Phase 3 trial in patients with second-line metastatic pancreatic cancer, continues its strong pace of enrollment in the U S following regulatory clearances in the E.U and Japan, we've also begun enrolling patients in those geographies. We are confident that we'll be able to substantially complete enrollment this year to enable an expected data readout in 2026.

我很高興地告訴大家，我們正在進行的針對二線轉移性胰腺癌患者的全球 3 期試驗 RASolute 302，在獲得歐盟和日本監管部門批准後，在美國繼續保持強勁的招募速度，我們也已經開始在這些地區招募患者。我們有信心今年能夠基本完成招生工作，以便在 2026 年獲得預期的數據讀數。

We are also currently activating study sites for RASolute 301, our Phase 3 trial in patients with previously treated RAS mutant non-small cell lung cancer.

我們目前也正在啟動 RASolute 301 的研究地點，這是我們針對先前接受過治療的 RAS 突變型非小細胞肺癌患者進行的 3 期試驗。

We're making good progress toward advancing daraxonrasib into earlier line randomized pivotal trials with planning underway to initiate registrational trials for daraxonrasib in first-line and adjuvant pancreatic cancer in the second half of this year.

我們在將 Daraxonrasib 推進到早期隨機關鍵試驗方面取得了良好進展，並計劃在今年下半年啟動 Daraxonrasib 在胰腺癌一線和輔助治療中的註冊試驗。

Today, we've shared important data that create exciting opportunities for us in both previously treated and first-line metastatic non-small cell lung cancer and eventually earlier lines of treatment, including treatment approaches that include our mutant selective inhibitors. We continue to expand our clinical programs and follow study patients to enable the initiation of one or more pivotal combination trials in 2026.

今天，我們分享了重要的數據，這些數據為我們在先前治療過的轉移性非小細胞肺癌和一線轉移性非小細胞肺癌以及最終的早期治療方法中創造了令人興奮的機會，包括採用我們的突變選擇性抑製劑的治療方法。我們將繼續擴大臨床計畫並追蹤研究患者，以便在 2026 年啟動一項或多項關鍵組合試驗。

Progressing our earlier stage pipeline, including advancing next generation innovations, continues to be an important priority. At AACR recently, our RMC-5127, our G12V mutant-selective RAS(ON) inhibitor was presented in the new drugs on the horizon session. We continue to advance the program and expect to reach a clinical stage later this year to enable the initiation of a Phase 1 study next year.

推動我們早期階段的研發管線，包括推動下一代創新，仍然是我們的重要優先事項。最近在 AACR 上，我們的 G12V 突變選擇性 RAS(ON) 抑制劑 RMC-5127 在即將出現的新藥會議上進行了展示。我們將繼續推進該計劃，並預計在今年稍後進入臨床階段，以便明年啟動第一階段的研究。

Finally, we continue to make substantial progress growing our commercial and operational capabilities and in advancing launch readiness activities in support of our first potential product launch. We are making good progress in building our commercialization capabilities in the United States across functions, including onboarding our US field medical team.

最後，我們繼續在提升商業和營運能力以及推動發布準備活動方面取得實質進展，以支持我們的第一個潛在產品發布。我們在美國各個職能領域的商業化能力建構方面取得了良好進展，包括組成美國現場醫療團隊。

We also recognize our important responsibility for ensuring patient access to daraxonrasib globally pending regulatory. I am very pleased to announce that Anthony Mancini, Revolution Medicines as our Chief Global Commercialization Officer and member of our senior management team. Anthony, who will oversee the comprehensive commercialization strategy and operations for our portfolio, brings substantial experience from his successful decades long career in the biotech and biopharmaceutical industry, having led significant product portfolios, launches and organizational builds in the US and major international markets as well as overseeing significant strategic partnerships. He will contribute additional strength, both to our approach to the US market and to our evaluation of options for reaching patients internationally.

我們也認識到，在監管期間，我們肩負著確保全球患者能夠獲得 daraxonrasib 的重要責任。我很高興地宣布，Revolution Medicines 的 Anthony Mancini 擔任我們的首席全球商業化長和高階管理團隊成員。安東尼將負責監督我們投資組合的全面商業化策略和運營，他在生物技術和生物製藥行業數十年的成功職業生涯中積累了豐富的經驗，曾領導美國和主要國際市場的重要產品組合、產品發布和組織建設，並負責監督重要的戰略合作夥伴關係。他將為我們進軍美國市場以及評估接觸國際患者的選擇貢獻更多力量。

Our vision remains to create the industry leading targeted-medicine franchise for patients with RAS-addicted cancers. This vision is built on three foundational pillars. First, our pioneering clinical stage RAS(ON) inhibitors have shown our discovery capabilities to be among the most innovative and productive in the industry.

我們的願景仍然是為 RAS 成癮癌症患者創建行業領先的標靶藥物特許經營權。這個願景建立在三大基礎支柱之上。首先，我們開創性的臨床階段 RAS(ON) 抑制劑已證明我們的發現能力是業內最具創新性和最高效的。

Second, our first-class development capabilities have been demonstrated by efficiently progressing multiple assets through first in human studies and advancing into late-stage development. Third, we are building high quality organizational capabilities to ensure we can successfully deliver products to patients.

其次，我們有效率地推進多項資產的首次人體試驗並進入後期開發，展現了我們一流的開發能力。第三，我們正在建立高品質的組織能力，以確保我們能夠成功地將產品送到患者手中。

Underlying all of this is an exceptionally strong financial position that gives us the wherewithal to continue executing on our strategy and solidifying our position as leaders in the treatment of patients with RAS-addicted cancers.

所有這一切的背後是我們異常強大的財務狀況，這為我們繼續執行我們的策略和鞏固我們在 RAS 成癮癌症患者治療領域的領先地位提供了必要的資金。

As we continue to deliver compelling clinical observations and build on our track record of execution, we never lose sight of our primary focus, patients living with cancer.

當我們繼續提供令人信服的臨床觀察並鞏固我們的執行記錄時，我們從未忘記我們的主要關注點——癌症患者。

Before we open the call for the Q&A session, I'd like to thank the patients and caregivers, clinical investigators, scientific and business collaborators, advisors and shareholders for their commitment. Without this support, none of the progress we've made would be possible.

在我們開始問答環節之前，我想感謝病人和照護者、臨床研究人員、科學和商業合作者、顧問和股東的承諾。如果沒有這種支持，我們所取得的任何進展都不可能實現。

I'd also like to recognize the extraordinary efforts of Revolution Medicines employees who embody tireless commitment to patients in the work they do every day.

我還要表彰 Revolution Medicines 員工的非凡努力，他們在每天的工作中體現了對病人的不懈承諾。

This concludes our prepared remarks for today, and I'll now turn the call over to the operator for the Q&A session.

今天的準備演講到此結束，現在我將把電話交給接線生進行問答環節。

(Operator Instructions) Michael Schmidt, Guggenheim.

（操作員指示）邁克爾施密特，古根漢。

Hi, thanks for taking my questions and congrats on all the progress. A lot of new information here to digest today. But I had a question on your first-line non-small cell lung cancer strategy. Obviously, there are interesting new data disclosed today for some of the various doublets. And based on your slide, it seems like for the KRAS G12C, first-line patient population, you're sort of focusing in on a triplet of elironrasib, daraxonrasib and pembrolizumab. Is probably the only combination where we haven't seen data yet today.

你好，感謝您回答我的問題，並祝賀您取得的所有進展。今天這裡有很多新資訊需要消化。但我對您的第一線非小細胞肺癌治療策略有一個疑問。顯然，今天披露了一些有關不同雙峰的有趣的新數據。根據您的幻燈片，對於 KRAS G12C 一線患者群體，您似乎主要關注 elironrasib、daraxonrasib 和 pembrolizumab 的三重療法。這可能是我們今天尚未看到數據的唯一組合。

But just looking at some of the other doublets, perhaps could you just comment on your confidence and tolerability of that triplet just based on some of the rash rates that we're seeing in some of the doublets and some of those reductions there?

但是，只看其他一些雙聯疫苗，也許您能否僅根據我們在一些雙聯疫苗中看到的皮疹發生率和其中的一些減少情況，評論一下您對該三聯疫苗的信心和耐受性？

Hi, Michael. Thanks for your question. Maybe Wei can speak to that.

你好，麥可。謝謝你的提問。也許魏先生可以談談這個問題。

We're optimistic given the profile we've seen so far. Obviously, we're still in the dose optimization and we have not yet defined the final dose for the triplet combination. I think we have characterized the monotherapy fairly well and we're not seeing any new safety signaling emerging. And regarding safety signaling that are known characterized such as rash, regarding daraxonrasib as well as the QTc, both are within what we have expected to observe with the monotherapy.

從目前看到的情況來看，我們感到樂觀。顯然，我們仍處於劑量優化階段，尚未確定三重療法的最終劑量。我認為我們已經相當很好地描述了單一療法，並且我們沒有看到任何新的安全信號出現。至於已知的安全訊號，例如皮疹、daraxonrasib 以及 QTc，均在我們預期透過單一療法觀察到的範圍內。

So I think when we have longer follow-up and define the dose, we'll be sharing those prior to initiating our Phase 3 trial.

因此我認為，當我們進行更長的追蹤並確定劑量時，我們會在開始第三階段試驗之前分享這些資訊。

Marc Frahm, TD Cowen.

馬克·弗拉姆（Marc Frahm），TD Cowen。

Hi, thanks for taking my questions and congrats on all of the data sets today. Maybe just looking across the various combination data sets you presented, I'm struck by, I mean, it looks like the vast majority of the responders are still ongoing as of the last data cutoff.

嗨，感謝您回答我的問題，並祝賀您今天獲得的所有數據集。也許只是瀏覽一下您提供的各種組合資料集，我會感到震驚，我的意思是，看起來絕大多數回應者在上次資料截止時仍在繼續。

Again, PFS is clearly immature, but maybe can you give us a sense of just kind of the average follow-up in those cohorts to maybe give a sense of where durability and PFS may be headed?

再次，PFS 顯然還不成熟，但也許您能讓我們了解這些群體的平均後續情況，以便了解耐用性和 PFS 的發展方向嗎？

And then kind of looking longer term, what type of data set do you think you need to gather before you can kind of formally declare Phase 3 intent for these various combinations? Do you just need to get a little bit more data to get more comfortable on safety and select the final dose? Or is it you need real robust PFS estimates? Just kind of what's needed there?

然後從長遠來看，您認為在正式宣布針對這些不同組合的第三階段意圖之前，需要收集哪種類型的資料集？您是否只需要獲得更多一點數據，以便更安全地選擇最終劑量？或者您需要真正的穩健的 PFS 估計？那裡需要什麼？

Hey, Marc. Thanks for your question. I think the first question really is something that refers back to the swimmer plots that we provided in December. And I think those are available. So I'd recommend just taking a look at those in terms of follow-up time for those.

嘿，馬克。謝謝你的提問。我認為第一個問題實際上與我們 12 月提供的游泳者圖表有關。我認為這些都是可行的。因此我建議只從後續時間的角度來看這些。

We don't have an update today on that because we haven't done a fresh data cut, but the December data had those duration of treatment parameters listed.

我們今天沒有對此進行更新，因為我們還沒有進行新的數據剪切，但 12 月的數據列出了治療持續時間參數。

Your main question I think is about what's really gating now to the triplet. Steve, you want to comment on that?

我認為你的主要問題是關於現在三胞胎的真正門檻是什麼。史蒂夫，你想對此發表評論嗎？

Yes. I mean, let's be clear that there's a differentiation here between the G12C program and the non-G12C program. The non-G12C program is pretty much ungated. It's more of a sort of operational execution type question. I think we've shown very conclusively that adding daraxonrasib to the KEYNOTE-189 schedule is tolerated and the efficacy is pretty impressive.

是的。我的意思是，讓我們明確一點，G12C 計劃和非 G12C 計劃之間存在區別。非 G12C 程序幾乎沒有限制。這更像是一種操作執行類型的問題。我認為我們已經非常明確地證明，將 daraxonrasib 添加到 KEYNOTE-189 計劃中是可以接受的，而且其療效非常令人印象深刻。

So we don't think we need any more data to press ahead with that. We just have to grind through the operational and regulatory milestones that you have to go through in order to get a study off the ground.

因此我們認為我們不需要更多的數據來繼續推進這項工作。我們只是需要努力完成必須經歷的營運和監管里程碑，以使研究順利進行。

As Wei alluded to in his prepared remarks, the G12C program is currently gated by optimizing the dose of that RAS(ON) doublet, the combination of daraxonrasib and elironrasib. Because it's a novel, novel combination and it's going into patients who have never received treatment for their non-small cell lung cancer. We really have to get the dose right -- to get the dose right to the satisfaction of the company, but also to the satisfaction of the regulators and the payers and the prescribers. So a little bit more refinement is needed there.

正如魏先生在其準備好的發言中提到的那樣，G12C 計劃目前透過優化 RAS(ON) 雙聯體（daraxonrasib 和 elironrasib 的組合）的劑量來控制。因為它是一種新穎的組合，並且適用於從未接受過非小細胞肺癌治療的患者。我們確實必須掌握正確的劑量——不僅要讓公司滿意，還要讓監管機構、付款人和處方人員滿意。因此，這裡需要進行一些進一步的改進。

We're pretty close. We have a range within which we're operating. And I don't think it will take too long, but that's essentially what's gating the G12C first-line non-small cell lung cancer program.

我們非常接近了。我們的營運範圍是固定的。我認為這不會花費太長時間，但這實際上是 G12C 一線非小細胞肺癌計劃的限制因素。

And a subpart of that was, is PFS required? Are we waiting for PFS? And I think that's a simple answer that. PFS is really not driving that decision. We understand PFS based on the second-line data, and now we have confidence that the response rates are very competitive. So I think we're good to go from that perspective.

其中一部分是，是否需要 PFS？我們在等待 PFS 嗎？我認為這是一個簡單的答案。PFS 實際上並沒有推動這項決定。我們根據二線數據了解 PFS，現在我們有信心，回應率非常具有競爭力。所以我認為從這個角度來看我們做得很好。

Yes. We should say we should add that both from the published literature and historical data and from our own very pretty intense in-house analysis, Response rate is a reasonable correlate of PFS in non-small cell lung cancer. That has not been the case for pancreatic cancer, but for lung cancer it is. So we're more confident about the link between our response rates that we've just disclosed in lung in the lung cancer patients and the predicted PFS that we will achieve.

是的。我們應該說，我們應該補充一點，無論是從已發表的文獻和歷史數據，還是從我們自己非常嚴格的內部分析來看，緩解率都是非小細胞肺癌 PFS 的合理相關因素。胰臟癌的情況並非如此，但肺癌的情況確實如此。因此，我們對剛揭露的肺癌患者肺癌緩解率與預計實現的 PFS 之間的關聯更有信心。

And of course, PFS in lung cancer more compelling as a regulatory endpoint unlike in pancreatic cancer where we have the overall survival. So lung cancer has got a lot more going for it.

當然，肺癌的 PFS 作為監管終點更具吸引力，這與胰臟癌的整體存活期不同。因此，肺癌的患病風險較高。

Thank you.

謝謝。

Eric Joseph, J.P. Morgan.

約瑟夫（Eric Joseph），摩根大通。

Thanks for taking the questions and let me also just concur. Lots of data updates here and a lot to digest. Maybe Steve, I could get you to expand a little bit on your last comment, the types of datasets, publications perhaps that grant you confidence that response rate higher response rates will be a predictor for better PFS outcomes, sort of outside of your own pipeline work.

感謝您回答這些問題，我也表示同意。這裡有大量數據更新，需要消化。也許史蒂夫，我可以請你稍微擴展一下你的最後一條評論，數據集的類型，出版物也許會讓你有信心，更高的響應率將可以預測更好的 PFS 結果，這有點超出你自己的流程工作範圍。

I'm also curious to know whether you are continuing to enroll the frontline lung cancer cohorts to sort of build upon the dataset that you are observing so far?

我還想知道您是否會繼續招募一線肺癌患者隊列，以建立您迄今為止觀察到的數據集？

And then we finally on the safety side, I know this is more than one question, but, on the safety side, this nonclinical, this subclinical QT signal that you're seeing with fairly wide combinations, you're confident that it won't become something greater with the triplet regimen? Thank you.

最後我們談談安全方面，我知道這不止一個問題，但是，在安全方面，您在相當廣泛的組合中看到的這種非臨床、亞臨床 QT 信號，您是否有信心它不會因三聯療法而變得更大？謝謝。

I think the first part was a question -- thank you, Eric. I think the first part was a question about the literature reflecting predictive utility of response rate for durability. I think we can provide some references offline. But by the way, it's something we've heard from investors for the last several years. Why don't we use response rates more? So I think it's pretty generally well known, and our observations are very consistent with that.

我認為第一部分是一個問題——謝謝你，埃里克。我認為第一部分是關於反映回應率對耐久性的預測效用的文獻的問題。我覺得我們可以線下提供一些參考。但順便說一句，這是我們過去幾年從投資者那裡聽到的事情。為什麼我們不更多地使用回應率？所以我認為這是眾所周知的，而且我們的觀察與此非常一致。

Do you have anything you want to add to that? What was the second part?

您還有什麼要補充的嗎？第二部分是什麼？

Do you want to comment on that?

你想對此發表評論嗎？

Yes. We have not seen that to be the case. Certainly, we've reported the QTc signal, it's fair. It's actually on par with even lower than what was monitored. Obviously, for longer follow-up and larger patient sample, we do not expect there is going to be an enhancement of QT. So I think QT is well within line of what osimertinib has reported in their label. So I don't think it will be.

是的。我們還沒有看到這樣的情況。當然，我們已經報告了 QTc 訊號，這是公平的。事實上，它與監測到的值相當，甚至更低。顯然，對於更長時間的追蹤和更大的患者樣本，我們預計 QT 不會增強。因此我認為 QT 完全符合奧希替尼在其標籤中報告的內容。所以我不認為會這樣。

And consistent with the larger earlier on and longer for elironrasib dataset that we showed at the beginning here, which I think makes that point pretty clear.

並且與我們一開始展示的更大、更長的 elironrasib 數據集一致，我認為這非常清楚地表明了這一點。

The other question was on whether you're continuing to enroll these chronic cohorts.

另一個問題是您是否會繼續招募這些慢性病患者。

Well, there's dose optimization, yes, ongoing, so pretty much answers that.

嗯，是的，正在進行劑量優化，所以基本上回答了這個問題。

Okay. Thanks for taking the questions. Congrats on the updates.

好的。感謝您回答這些問題。恭喜更新。

Thank you.

謝謝。

Jonathan Chang, Leerink Partners.

Jonathan Chang，Leerink Partners。

Hi, guys. Thanks for taking my question. How are you thinking about the duration of clinical benefit of daraxonrasib versus the mutant-selective inhibitors like zoldonrasib and elironrasib? What are the reasons for why one could be more durable than the other? And how could this and other factors impact how you're thinking about future development strategies? Thank you.

嗨，大家好。感謝您回答我的問題。您如何看待 Daraxonrasib 與 zoldonrasib 和 elironrasib 等突變選擇性抑制劑相比的臨床益處持續時間？為什麼其中一種材料比另一種更耐用？原因何在？這些因素和其他因素會如何影響您對未來發展策略的思考？謝謝。

Thanks, Jonathan. Maybe I'll comment on that and then if Steve Wai wants to add anything to it. I don't think we have any direct head-to-head comparison because the daraxonrasib study was done in tumors that carry different mutations than the elironrasib study. So we really can't compare those. So we can't say which is superior to the other and they're not matched for other prognostic factors as well. So I don't think we have any information on it.

謝謝，喬納森。也許我會對此發表評論，然後看看 Steve Wai 是否想補充任何內容。我認為我們沒有任何直接的頭對頭比較，因為 daraxonrasib 研究是在與 elironrasib 研究攜帶不同突變的腫瘤中進行的。所以我們真的無法比較它們。因此，我們無法說哪一個優於另一個，而且它們也不符合其他預後因素。所以我認為我們對此沒有任何資訊。

If you're wondering what we might predict, I don't know. We'll see. And ultimately, we're combining these anyway as both Wei and Steve have talked about. And so one ought to get the benefit of whatever the pros are on each side of that.

如果你想知道我們可能會預測什麼，我不知道。我們將拭目以待。最終，我們會將這些結合起來，正如魏和史蒂夫所談到的。因此，無論雙方有何利弊，都應該從中獲益。

Is there anything more specific that you're trying to get out there?

還有什麼更具體想表達的嗎？

I was just thinking about how in in in situations where you might be considering, advancing the multi-RAS or a mutant-selective one or maybe the combination of both, how you might consider things like duration of clinical benefit and how long patients may stay on treatment, in addition to other considerations?

我只是在想，在您可能考慮推進多 RAS 或突變選擇性 RAS 或兩者結合的情況下，除了其他考慮因素之外，您還會如何考慮臨床獲益的持續時間以及患者可以接受治療多長時間？

It's the number one consideration. Because that's the key driver of the sort of patient experience, assuming that we obviously have a combination that patients can tolerate for the time that they're on the treatment without having a miserable life. It's the number one consideration.

這是首要考慮因素。因為這是患者體驗的關鍵驅動因素，假設我們顯然有一個組合，患者在接受治療期間可以忍受，而不會過著痛苦的生活。這是首要考慮因素。

The mechanisms of escape from the mutant-selective inhibitors are very different from the mechanisms of escape from daraxonrasib. We have only disclosed mechanism of escape data for daraxonrasib in pancreatic cancer, but it's very different pattern of escape from what's being disclosed for mutant-selective inhibitors in non-small cell lung cancer. And that's why we're so enthusiastic about the combination, because all of those putative mechanisms of escape are covered by the combination.

突變選擇性抑制劑的逃脫機制與 daraxonrasib 的逃脫機制非常不同。我們僅揭露了達拉松拉西佈在胰臟癌中的逃脫機制數據，但其逃脫模式與非小細胞肺癌中突變選擇性抑制劑的逃脫模式非常不同。這就是我們對這種組合如此熱衷的原因，因為所有那些假定的逃逸機制都被這種組合所涵蓋。

The novel RAS mutations that emerge on the mutant selective inhibitors are inhibited by daraxonrasib and the putative amplification of mutant KRAS that we might see in lung cancer, which we have seen in pancreatic cancer, is suppressed by hitting the mutant harder with the combination of the two RAS on inhibitors together. So we do expect the PFS to be longer with the combo than with either agent alone. And as we described, the increase in response rate is a good harbinger of that. We just have to wait for that data to mature in order for it to be worthwhile disclosing publicly because immature PFS data isn't helpful to anybody.

突變選擇性抑制劑上出現的新型 RAS 突變被 daraxonrasib 抑制，而我們可能在肺癌中看到的突變 KRAS 的假定擴增（我們在胰腺癌中看到過）則通過結合使用兩種 RAS 抑製劑對突變進行更有力的打擊而受到抑制。因此，我們確實預期該組合藥物的 PFS 會比單獨使用任何一種藥物更長。正如我們所描述的，回應率的提高就是一個很好的預兆。我們只需要等待資料成熟，以便值得公開揭露，因為不成熟的 PFS 資料對任何人都沒有幫助。

Yes. And Steve's comments are entirely consistent with what we have reported in the preclinical context. And I think Wei showed two figures, representative of a much larger dataset that we presented over several scientific meetings that the combination does tend to deliver significantly greater benefit and including the figure on the right side of that slide, I'm not sure what it is in your deck, but that right figure shows the combination of the doublet plus anti PD-1 basically provided for no progression in any of the animals in that experiment across 100 days. So I think the totality of the evidence is supportive of what Steve suggested.

是的。史蒂夫的評論與我們在臨床前報告中所報告的內容完全一致。我認為魏先生展示了兩個數字，代表了我們在幾次科學會議上提出的更大的數據集，表明這種組合確實往往會帶來更大的益處，包括幻燈片右側的數字，我不確定您的幻燈片中是什麼，但右邊的數字顯示了雙聯體加抗 PD-1 的組合基本上沒有導致該實驗中的任何動物在 100 天內出現任何進展。所以我認為所有證據都支持史蒂夫的說法。

Got it. Thanks for taking the question.

知道了。感謝您回答這個問題。

Thank you.

謝謝。

Kelly Shi, Jefferies.

Kelly Shi，傑富瑞集團。

Hi, this is Clara on for Kelly. Thanks for taking our question. Congrats on the data. So for non-small cell lung cancer with all the combination updates and it seems like you have really multiple paths to pursue the opportunity in lung and you also have total pancreatic development as well as maybe other early initiatives such as G12V.

大家好，我是克拉拉，為凱利服務。感謝您回答我們的問題。恭喜數據。因此，對於非小細胞肺癌，有了所有的組合更新，似乎您真的有多種途徑來尋求肺癌的機會，並且您還可以進行全面的胰腺開發以及其他早期舉措，例如 G12V。

So maybe from a resource allocation perspective, what are the key criteria driving priorities between all those developments.

因此，從資源分配的角度來看，推動所有這些發展優先事項的關鍵標準是什麼。

And also for lung cancer specifically, how should we think about the cadence of initiating pivotal combination trials? And you mentioned you might initiate combination trials in 2026. Thank you.

具體來說，對於肺癌來說，我們該如何考慮啟動關鍵組合試驗的節奏？您提到可能會在 2026 年開始組合試驗。謝謝。

Okay. Thank you, Clara. Let me start with the second comment about timing. I mean, we have provided some timing, and I think that's all we can provide today. We do have, of course, daraxonrasib in non-small cell lung cancer already underway in the 301 study. But then in terms of first-line and combination studies, we'd expect to begin rolling those out in 2026.

好的。謝謝你，克拉拉。讓我先談談關於時間的第二條評論。我的意思是，我們已經提供了一些時間，我認為這就是我們今天所能提供的全部。當然，我們已在 301 項研究中對非小細胞肺癌進行了 daraxonrasib 治療。但就一線和聯合研究而言，我們預計將於 2026 年開始推出。

In terms of resource allocation, I don't think there's a simple single word or sentence answer to help clarify that for you. It's obviously a pretty complex and rich set of opportunities. It's sort of an embarrassment of riches that each clinical study we've done so far opens up pretty exciting new pivotal trials that we could consider doing.

在資源分配方面，我認為沒有一個簡單的單字或句子的答案可以幫助你澄清這一點。這顯然是一個相當複雜且豐富的機會。令人欣喜的是，迄今為止我們所做的每一項臨床研究都開啟了我們可以考慮進行的相當令人興奮的新關鍵試驗。

So it certainly does create some need for prioritization. We start with the clinical data, the biological rationale behind the data. We look at the competitive landscape. As Steve pointed out, ultimately what's most important is to provide durable clinical benefit. So that's a key characteristic that gets ranked in all of this.

因此它確實產生了一些優先排序的需要。我們從臨床數據、數據背後的生物學原理開始。我們觀察一下競爭格局。正如史蒂夫指出的那樣，最終最重要的是提供持久的臨床益處。所以這是在所有這些中排名的一個關鍵特徵。

So many, many factors. And at this point, we're able to proceed with a large chunk of the priorities that we have defined. We're basically moving everything forward right now that is ready to be moved forward in 2025, and we'll continue to do that into 2026, constantly looking at justification for the investments, but also trying to achieve the goal that we've alluded to several times here, which is to deliver significant changes on behalf of patients across RAS mutations, tumor types and lines of therapy, and we think we're best positioned in the industry to do that.

有很多很多的因素。此時，我們可以繼續執行已確定的大部分優先事項。我們現在基本上正在推進所有準備在 2025 年推進的項目，並且我們將繼續這樣做到 2026 年，不斷尋找投資的合理性，同時也試圖實現我們在這裡多次提到的目標，即為 RAS 突變、腫瘤類型和治療方案的患者帶來重大改變，我們認為我們在行業中處於最佳位置來做到這一點。

Ellie Merle, UBS.

瑞銀的艾莉·梅爾（Ellie Merle）。

Hey, guys. Thanks for taking the question and congrats on all the progress. Just curious your latest thinking on a potential commercial strategy ex-US and your general philosophy around potential partnering.

嘿，大家好。感謝您提出這個問題，並祝賀您取得的所有進展。我只是好奇您對美國以外潛在商業策略的最新想法以及您對潛在合作夥伴關係的整體理念。

And then just in terms of the designs for the pivotal combination, trial or trials. Could you give us maybe any more color on when you might expect to meet with the FDA to discuss the designs and when we might be able to learn more about the specifics of the designs from our end? Thanks.

然後僅就關鍵組合、試驗或試驗的設計而言。您能否告訴我們更多關於您預計何時與 FDA 會面討論設計以及我們何時可以從我們的角度了解更多有關設計細節的信息？謝謝。

Hi, Ellie. Thanks for your question. On the second point, unfortunately, no, we don't typically sort of lay out the timeline for our future interactions or ongoing interactions with the FDA. Our pattern that we try to establish is once we definitize a plan or close to a definitive plan, we often provide some sort of update including the data to support whatever commitment we're making. But beyond that, I can't give you any further higher resolution answer to it.

你好，艾莉。謝謝你的提問。關於第二點，很遺憾，我們通常不會為未來與 FDA 的互動或正在進行的互動制定時間表。我們試圖建立的模式是，一旦我們確定了計劃或接近確定的計劃，我們通常會提供某種更新，包括數據來支持我們所做的承諾。但除此之外，我無法給你任何更高解析度的答案。

With regard to the ex-US strategy, that's obviously very much on our minds as I think it is on our investors. Since I first raised almost two years ago now the possibility that we might engage with others to help us commercialize outside the US, while we would certainly focus on retaining the US market. We have had strong interest from multiple global pharma companies. We've had concrete and productive dialogue with them. And without a doubt, we could enter an attractive partnership and that's really creates a great deal of optionality for us.

關於美國以外的策略，這顯然是我們非常關心的問題，我認為這也是我們的投資者非常關心的問題。自從大約兩年前我第一次提出我們可能與其他公司合作來幫助我們在美國以外商業化的可能性以來，我們肯定會專注於保留美國市場。我們已引起多家全球製藥公司的濃厚興趣。我們與他們進行了具體、有成效的對話。毫無疑問，我們可以建立一種有吸引力的合作關係，這確實為我們創造了許多選擇空間。

We've also felt no need to rush into such a partnership and we've continued to use time to our advantage. We've continued tracking the portfolio, tracking the assets, progress trajectory. We've also tracked organizational progress and trajectory and all of those have continued to exceed our expectations. So now we're in the position to assess the pros and cons of all the options that are available to us. And we have to make a strategic judgment, which we're just not ready to make today, which is what's the best approach for serving patients not only in the US, but also internationally and that also serves our business.

我們也認為沒有必要倉促建立這樣的合作關係，我們會繼續利用時間發揮我們的優勢。我們一直在追蹤投資組合、資產和進展軌跡。我們還追蹤了組織的進展和軌跡，所有這些都超出了我們的預期。所以現在我們可以評估所有可用選項的優缺點。我們必須做出戰略判斷，而我們今天還沒有準備好做出這一判斷，那就是什麼是服務於不僅在美國而且在國際上患者的最佳方法，這也有利於我們的業務。

And we are continuing to look at that, but now through the lens of where we are in 2025 with a very different organization in terms of depth and breadth, programs -- maturity programs and also with the addition now of Anthony, who joins the team and can bring a very broad commercial perspective to it as well.

我們將繼續關注這個問題，但現在我們將從 2025 年的角度來看待這個問題，我們將擁有一個在深度和廣度、計劃（成熟度計劃）方面截然不同的組織，而且現在安東尼也加入了團隊，他可以給團隊帶來非常廣闊的商業視角。

So we will complete that analysis at some point and continue to provide updates as appropriate.

因此，我們將在某個時候完成該分析，並繼續提供適當的更新。

Great. Thanks.

偉大的。謝謝。

Thank you. This now concludes the question-and-answer session. I would now like to turn it back to Mark Goldsmith for closing remarks.

謝謝。問答環節到此結束。現在我想請馬克‧戈德史密斯作最後發言。

Thank you, operator. Thanks to everyone for participating today and for your continued support of Revolution Medicines.

謝謝您，接線生。感謝大家今天的參與以及對 Revolution Medicines 的持續支持。

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

感謝大家參加今天的會議。該計劃確實就此結束。您現在可以斷開連線。