Revolution Medicines Inc (RVMD) 2025 Q3 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Revolution Medicines Q3 2025 earnings conference call. (Operator Instructions) Please be advised that today's conference is being recorded.

您好，感謝您的耐心等待。歡迎參加 Revolution Medicines 2025 年第三季財報電話會議。（操作人員指示）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.

現在我謹將會議交給今天的第一位發言人，企業事務高級副總裁瑞安·阿塞。請繼續。

Thank you, and welcome to our third-quarter 2025 earnings call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer; Dr. Wei Lin, our Chief Medical Officer; and Jack Anders, our Chief Financial Officer; Dr. Steve Kelsey, our President of Research and Development, Dr. Alan Sandler, our Chief Development Officer; and Anthony Mancini, our Chief Global Commercialization Officer will join us for the Q&A portion of today's call.

謝謝大家，歡迎參加我們2025年第三季財報電話會議。今天與我一同參加電話會議的有：Revolution Medicine 董事長兼首席執行官 Mark Goldsmith 博士；首席醫療官 Wei Lin 博士；首席財務官 Jack Anders；研發總裁 Steve Kelsey 博士；首席開發官 Alan Sandler 博士；以及首席全球商業化官 Anthony Mancini，他將參加今天電話會議的問答環節。

I'd 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, 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. This afternoon, we released financial results for the quarter ended September 30, 2025, and recent corporate updates.

我想告知各位，我們在本次電話會議中所做的某些陳述屬於前瞻性陳述，因為這些陳述涉及未來事件，並受到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完整討論，請參閱我們向美國證券交易委員會提交的 10-K 表格年度報告和 10-Q 表格季度報告。今天下午，我們發布了截至 2025 年 9 月 30 日的季度財務業績以及最近的公司動態。

The press release and updated corporate presentation are available on the Investors section of our website at revmed.com.

新聞稿和更新後的公司介紹可在我們網站 revmed.com 的投資者關係部分查看。

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

接下來，我將把電話交給 Revolution Medicine 的董事長兼執行長 Mark Goldsmith 博士。標記？

Thanks, Ryan, and good afternoon. At Revolution Medicines, we are tireless in our commitment to revolutionizing treatment for patients with RAS-addicted cancers through the discovery, development, and delivery of innovative targeted medicines. With robust operational capabilities, financial strength, and the compelling clinical stage RAS(ON) inhibitors, we are building the leading global RAS-targeted medicines franchise that we believe has the potential to transform treatment for patients living with pancreatic, lung and colorectal cancers. In the quarter, we continued to make substantial progress as we scale the organization and advance our pipeline to fulfill our global development and commercialization ambitions.

謝謝你，瑞恩，下午好。Revolution Medicines 致力於透過發現、開發和提供創新標靶藥物，徹底改變 RAS 成癮癌症患者的治療方式，我們為此不懈努力。憑藉強大的營運能力、雄厚的財力和極具吸引力的臨床階段 RAS(ON) 抑制劑，我們正在打造全球領先的 RAS 標靶藥物產品線，我們相信該產品線有潛力改變胰腺癌、肺癌和結直腸癌患者的治療方式。本季度，我們在擴大組織規模和推進產品線以實現全球開發和商業化目標方面繼續取得實質進展。

Today, we'll begin by highlighting recent progress across our pipeline, beginning with daraxonrasib in pancreatic cancer. I'd like to note that daraxonrasib has received three special designations from the FDA, recognizing its potential role in treating patients with pancreatic cancer an aggressive disease that is nearly always caused by a RAS mutation. Previously, daraxonrasib was awarded breakthrough therapy status. And recently, it received both orphan drug designation and an FDA commissioner's national priority voucher for accelerating review of a new drug application. These highlights the significant unmet medical needs in pancreatic cancer, and the potential of this investigational drug to transform treatment for patients living with this devastating disease.

今天，我們將首先重點介紹我們研發管線近期取得的進展，首先是用於治療胰臟癌的 daraxonrasib。我想指出，daraxonrasib 已獲得 FDA 的三項特殊認定，這認可了其在治療胰腺癌患者方面的潛在作用，胰腺癌是一種侵襲性疾病，幾乎總是由 RAS 突變引起的。在此之前，daraxonrasib 被授予突破性療法認定。最近，該藥物獲得了孤兒藥資格認定和美國食品藥物管理局局長頒發的國家優先券，用於加快新藥申請的審查。這凸顯了胰臟癌領域尚未滿足的重大醫療需求，以及這種試驗性藥物改變患有這種毀滅性疾病的患者治療方式的潛力。

I'd like to invite Dr. Wei Lin to walk through our most recent clinical updates in pancreatic cancer, Wei?

我想邀請魏琳博士為我們介紹我們在胰臟癌領域的最新臨床進展，魏？

Thanks, Mark. Daraxonrasib our RAS(ON) multi-selective inhibitor with a promising clinical profile in multiple indications, including pancreatic cancer. In September, we presented long-term follow-up data from the Phase 1 daraxonrasib monotherapy cohort of patients with second-line metastatic pancreatic cancer. These results reinforce our understanding of the strong clinical antitumor activity and durability. The acceptable safety and tolerability profile remained consistent with earlier findings with no new safety signals observed.

謝謝你，馬克。Daraxonrasib 是一種 RAS(ON) 多選擇性抑制劑，在包括胰腺癌在內的多種適應症中具有良好的臨床前景。9 月，我們公佈了 daraxonrasib 單藥治療二線轉移性胰腺癌患者的 1 期臨床試驗隊列的長期追蹤數據。這些結果進一步加深了我們對該藥物強大的臨床抗腫瘤活性和持久性的理解。安全性和耐受性良好，與先前的研究結果一致，未觀察到新的安全訊號。

Slide 10 shows that with longer follow-up, durability outcomes remained encouraging. The estimated median progression-free survival for patients with both the RAS G12X and all RAS-mutant groups exceeded eight months. The estimated median overall survival was 13.1 months and 15.6 months for patients in the G12X and RAS-mutant groups, respectively, with a lower bound of 95% confidence interval at approximately 11 months.

第 10 張投影片顯示，隨著追蹤時間的延長，持久性結果仍然令人鼓舞。RAS G12X 突變組和所有 RAS 突變組患者的估計中位無惡化存活期超過 8 個月。G12X 突變組和 RAS 突變組患者的估計中位總存活期分別為 13.1 個月和 15.6 個月，95% 信賴區間的下限約為 11 個月。

These results are particularly compelling, especially in the context of standard of care cytotoxic chemotherapy regimens that were reported in randomized controlled trials to provide a median over survival of six to seven months in the second line. And approximately 11 months in the first-line setting.

這些結果尤其令人信服，尤其是在隨機對照試驗中報告的標準治療細胞毒性化療方案僅能使二線患者的中位存活期達到六至七個月的情況下。一線治療大約需要 11 個月。

RASolute 302, our Phase 3 registrational trial in patients with second-line metastatic PDAC, is winding down enrollment globally as we near completion of enrollment across all US and international sites. We remain on track for an expected data readout in 2026. In September, we also shared encouraging initial results for daraxonrasib in first-line metastatic pancreatic cancer, both as monotherapy and in combination with standard care chemotherapy.

RASolute 302 是我們正在進行的針對二線轉移性 PDAC 患者的 3 期註冊試驗，隨著我們在美國和國際所有試驗點的招募工作接近完成，該試驗在全球範圍內的招募工作正在逐步減少。我們仍有望在 2026 年獲得預期的數據。9 月，我們也分享了 daraxonrasib 在一線轉移性胰腺癌治療中令人鼓舞的初步結果，無論是作為單藥治療還是與標準治療化療聯合治療。

As shown in slide 11, daraxonrasib monotherapy induced tumor regressions in most patients with an objective response rate of 47% and disease control rate of 89%. The majority of patients remained on-site treatment as of the data cutoff. While the data were not sufficiently mature to estimate the median progression-free survival or overall survival, we continue to follow these patients to assess the durability of clinical benefit. The acceptable safety profile of daraxonrasib monotherapy in the first-line metastatic setting, was generally consistent with what has been reporting in patients with second-line metastatic disease.

如幻燈片 11 所示，daraxonrasib 單藥治療使大多數患者的腫瘤消退，客觀緩解率為 47%，疾病控制率為 89%。截至數據截止日期，大多數患者仍在現場接受治療。雖然數據尚不足以估計中位無惡化存活期或總存活期，但我們將繼續追蹤這些患者，以評估臨床效益的持久性。daraxonrasib 單藥治療在轉移性疾病一線治療中具有可接受的安全性，這與二線轉移性疾病患者的報告結果基本一致。

On slide 12, the combination of daraxonrasib plus gemcitabine, nab-paclitaxel, or GnP, chemotherapy also delivered significant antitumor activity, represented by deep and sustained tumor regressions. With a rejected response rate of 55% and disease control rate of 90%. Both patients remained on treatment as of the data cutoff. Again, longer follow-up is required to estimate median progression-free survival and overall survival.

在第 12 張投影片中，daraxonrasib 與吉西他濱、nab-紫杉醇或 GnP 化療的組合也表現出顯著的抗腫瘤活性，表現為腫瘤深度和持續性消退。拒絕率達 55%，疾病控制率達 90%。截至數據截止日期，兩名患者仍在接受治療。同樣，需要更長時間的追蹤來估計中位無惡化存活期和總存活期。

As with monotherapy, the combination regimen showed an acceptable safety profile. The rates of premium related adverse events were additive of the individual agents. No new safety signals were observed. We expect to share updated data from patients treated with daraxonrasib with or without GnP in first-time PDAC, including preliminary durability in the first half of 2026.

與單藥治療一樣，聯合治療方案也顯示出可接受的安全性。與保費相關的各種不良事件的發生率是各個代理人的發生率相加的。未發現新的安全訊號。我們預計將於 2026 年上半年分享接受達拉西布（daraxonrasib）治療（無論是否聯合 GnP）的初次 PDAC 患者的最新數據，包括初步的持久性數據。

But on the encouraging early phase data in the first line and second settings, we are advancing RASolute 303, a randomized three-arm Phase 3 trial in patients with first-line metastatic PDAC, as shown on slide 13. This recreational trial will compare daraxonrasib monotherapy or daraxonrasib plus GnP followed by daraxonrasib monotherapy to a comparator arm of GnP low.

但根據第一線和二線治療中令人鼓舞的早期階段數據，我們正在推進 RASolute 303，這是一項針對一線轉移性 PDAC 患者的隨機三臂 3 期試驗，如幻燈片 13 所示。這項娛樂性試驗將比較達拉西單藥治療或達拉西加 GnP 治療後再進行達拉西單藥治療與低劑量 GnP 對照組的療效。

The design of this three-arm study provides two distinct opportunities to demonstrate potential survival benefit for patient: treatment with daraxonrasib as monotherapy in first line, followed eventually by chemotherapy in second line, or alternatively, treating concurrently with both daraxonrasib and chemotherapy in first line. Both strategies have scientific and clinical merit and deserve to be evaluated. We remain on track to initiate RASolute 303 this year. I'd like to provide an overview of the current standard of care in the setting of resectable PDAC.

這項三臂研究的設計提供了兩種不同的機會來證明患者的潛在生存益處：一線使用達拉西單藥治療，二線最終進行化療；或者，一線同時使用達拉西和化療進行治療。這兩種策略都具有科學和臨床價值，值得評估。我們仍按計畫於今年啟動 RASolute 303 計畫。我想概述目前可切除胰臟導管腺癌的治療標準。

Of surgery, along with perioperative chemotherapy offers patients the possibility of a cure. The relapse rate is high at approximately 80%. The current standard care for perioperative treatment is cytotoxic chemotherapy, either modify FOLFIRINOX, or gemcitabine, capecitabine. The publicly reported disease-free survival rate on these chemotherapy regimens ranges from 13.9 months to 21.6 months.

手術結合圍手術期化療，為患者提供了治癒的可能性。復發率高達約 80%。目前圍手術期治療的標準療法是細胞毒性化療，包括改良的 FOLFIRINOX 方案、吉西他濱或卡培他濱。公開通報的這些化療方案的無疾病存活期為 13.9 個月至 21.6 個月。

Our three-year disease-free survival ranges from approximately 20% to 40%. We believe there remains significant room for improvement that may be served with RAS-targeted therapy. The strength of the daraxonrasib monotherapy data so far in both first and second-line metas disease provides a compelling rationale for advancing daraxonrasib into the Aspen setting.

我們的三年無病存活率約為 20% 至 40%。我們認為，RAS標靶治療可能有助於進一步改善病情，但仍有很大的提升空間。迄今為止，daraxonrasib 單藥治療在一線和二線轉移性疾病中的強大療效數據，為將 daraxonrasib 推進到 Aspen 治療方案中提供了令人信服的理由。

And slide 15 shows our Phase 3 trial design, RASolute 304 in perioperative therapy. We plan to evaluate approximately 500 patients after surgical reception and 4 months or more parotid therapy with the local standard of care, either FOLFIRINOX or gemcitabine, capecitabine, [and answered] before and/or after surgery.

第 15 張投影片展示了我們的 3 期試驗設計，RASolute 304 在圍手術期治療中的應用。我們計劃對接受手術治療和 4 個月或更長時間的腮腺治療（採用當地標準治療方案，即 FOLFIRINOX 或吉西他濱、卡培他濱）的患者進行評估，並在手術前和/或手術後進行回答。

Patients will be randomized to either observation or drug from daraxonrasib monotherapy 300 milligrams daily for two years. The primary endpoint will be disease-free survival with secondary endpoints of overall survival and safety. We have initiated this trial and site activation is currently underway.

患者將被隨機分配到觀察組或藥物組，接受達拉西單藥治療，每日 300 毫克，持續兩年。主要終點為無疾病存活期，次要終點為總存活期和安全性。我們已經啟動了這項試驗，目前試驗場地正在啟用。

I'll also touch briefly on zoldonrasib our covalent RAS(ON) G12D selective covalent inhibitor in pancreatic cancer. Zoldonrasib has demonstrated a compelling clinical profile with encouraging anti-tumor activity and a particularly favorable safety tolerability profile. With this differentiated profile, we believe zoldonrasib as high potential to contribute as a key component of a combination therapy in first-line PDAC with current standard care chemotherapy and/or with daraxonrasib, as a RAS(ON) inhibitor doublet.

我也會簡單介紹一下zoldonrasib，我們用於治療胰臟癌的共價 RAS(ON) G12D 選擇性共價抑制劑。Zoldonrasib 已展現出令人信服的臨床特性，具有令人鼓舞的抗腫瘤活性和特別良好的安全性耐受性。憑藉這種差異化的特性，我們認為 zoldonrasib 具有很高的潛力，可以作為一線 PDAC 聯合治療的關鍵組成部分，與目前的標準治療化療和/或 daraxonrasib（一種 RAS(ON) 抑製劑雙藥）聯合使用。

The potential for this doublet was featured at last month's triple meeting. For new preclinical data demonstrated that the combination of zoldonrasib with daraxonrasib can maximally inhibit RAS G12D and improve both the depth and durability of response. We expect to initiate our first zoldonrasib combination registrational trial in first-line metastatic PDAC in the first half of 2026. We look forward to share the trial details and additional supporting data around that timeframe.

上個月的三重奏會議上，這兩項賽事的潛力得到了充分展現。新的臨床前數據顯示，zoldonrasib 與 daraxonrasib 聯合使用可以最大限度地抑制 RAS G12D，並提高反應的深度和持久性。我們預計將於 2026 年上半年啟動首個針對第一線轉移性 PDAC 的 zoldonrasib 聯合註冊試驗。我們期待在屆時分享試驗詳情及其他相關數據。

I'll now return the call to our CEO. Mark?

我現在就回電給執行長。標記？

Thank you, Wei, following closely behind pancreatic cancer, our non-small cell lung cancer clinical program remains an area of strategic priority, and we are progressing well in our efforts.

謝謝魏，繼胰臟癌之後，我們的非小細胞肺癌臨床計畫仍然是戰略重點領域，我們在相關工作中取得了良好進展。

Focusing first on daraxonrasib. The RASolute 301 registrational trial studying daraxonrasib versus docetaxel in previously treated patients with RAS-mutant non-small cell lung cancer continues to enroll patients across sites in the US and is now also enrolling in Europe and Japan. We also continue advancing plans to initiate a registrational trial in the first-line metastatic setting in 2026, evaluating daraxonrasib in combination with pembrolizumab and chemotherapy, and we expect to disclose study details around the time of initiation. As a reminder, this plan was based on the encouraging initial data we presented in May showing the combination of daraxonrasib with pembrolizumab with or without chemotherapy was well tolerated and demonstrated encouraging early antitumor activity.

首先重點關注daraxonrasib。RASolute 301 註冊試驗正在研究 daraxonrasib 與多西他賽在先前接受過治療的 RAS 突變型非小細胞肺癌患者中的療效，該試驗繼續在美國各地招募患者，目前也在歐洲和日本招募患者。我們也將繼續推進計劃，於 2026 年啟動一線轉移性治療註冊試驗，評估 daraxonrasib 與 pembrolizumab 和化療聯合治療的效果，我們預計將在試驗啟動前後公佈研究詳情。提醒一下，該計劃是基於我們在 5 月公佈的令人鼓舞的初步數據，數據顯示達拉西布與帕博利珠單抗聯合或不聯合化療的耐受性良好，並顯示出令人鼓舞的早期抗腫瘤活性。

In the G12C non-small cell lung cancer space, we continue to make progress with elironrasib, our RAS(ON) G12C inhibitor. Last month, at the triple meeting, we presented encouraging monotherapy data in heavily pretreated patients with G12C non-small cell lung cancer who had received a median of 3 prior lines of therapy, including treatment with a G12C inhibitor.

在 G12C 非小細胞肺癌領域，我們的 RAS(ON) G12C 抑制劑 elironrasib 持續取得進展。上個月，在三方會議上，我們展示了令人鼓舞的單藥治療數據，該數據針對的是接受過大量預處理的 G12C 非小細胞肺癌患者，這些患者此前接受過平均 3 線治療，包括 G12C 抑製劑治療。

As shown on slide 22, elironrasib demonstrated a confirmed objective response rate of 42%, a disease control rate of 79% and a median duration of response of 11.2 months.

如投影片 22 所示，elironrasib 的確認客觀緩解率為 42%，疾病控制率為 79%，中位緩解持續時間為 11.2 個月。

On slide 23, the median progression-free survival was 6.2 months in these heavily pretreated patients. While the median overall survival had not yet been reached, 62% of patients were alive at 12 months. We are encouraged by the strength of these data in late-line KRAS G12C(OFF) inhibitor experienced patients and continue to expand enrollment in this and other elironrasib monotherapy in combination studies, while exploring a number of options for continued development of this differentiated RAS(ON) G12C selective inhibitor.

投影片 23 顯示，這些接受過大量預先治療的患者的中位無惡化存活期為 6.2 個月。雖然尚未達到中位總存活期，但 12 個月時仍有 62% 的患者存活。我們對這些數據在接受 KRAS G12C(OFF) 抑制劑治療的晚期患者中的有效性感到鼓舞，並將繼續擴大該藥物和其他 elironrasib 單藥治療聯合研究的入組人數，同時探索繼續開發這種差異化的 RAS(ON) G12C 選擇性抑制劑的多種選擇。

Regarding zoldonrasib in lung cancer, we are evaluating a Phase 1 monotherapy expansion cohort of patients with previously treated non-small cell lung cancer, as well as exploring combination regimens, including zoldonrasib with pembrolizumab and zoldonrasib with daraxonrasib. In addition to plans mentioned earlier to initiate a registrational trial for a zoldonrasib combination in patients with first-line metastatic pancreatic cancer in the first half of 2026, we expect to initiate one or more additional pivotal combination trials in 2026 to incorporate either zoldonrasib or elironrasib.

關於 zoldonrasib 在肺癌中的應用，我們正在評估一項針對既往接受過治療的非小細胞肺癌患者的 1 期單藥治療擴展隊列研究，並探索聯合治療方案，包括 zoldonrasib 與 pembrolizumab 聯合治療以及 zoldonrasib 與 daraxonrasib 聯合治療。除了先前提到的在 2026 年上半年啟動針對一線轉移性胰腺癌患者的 zoldonrasib 聯合療法註冊試驗的計劃外，我們預計在 2026 年啟動一項或多項額外的關鍵性聯合療法試驗，將 zoldonrasib 或 elironrasib 納入其中。

We also continue to advance RMC-5127, an oral tri-complex RAS(ON) G12V selective inhibitor. As a reminder, approximately 48,000 patients are diagnosed with a KRAS G12V mutant cancer in the US each year, including non-small cell lung cancer and gastrointestinal cancers, such as pancreatic and colorectal. RMC-5127 has been shown to induce deep and durable regressions in preclinical models, and it has been advancing towards clinical development.

我們也將繼續推進 RMC-5127 的研發，RMC-5127 是一種口服三複合物 RAS(ON) G12V 選擇性抑制劑。提醒大家，美國每年約有 48,000 名患者被診斷出患有 KRAS G12V 突變癌症，其中包括非小細胞肺癌和胃腸道癌症，如胰腺癌和大腸癌。RMC-5127 已被證明能在臨床前模型中誘導深度和持久的退化，並且一直在向臨床開發方向發展。

We are on track to initiate the planned first-in-human trial in Q1 2026. Based on the progress we've made across our three clinical stage assets, we are confident in the potential of our RAS(ON) inhibitor portfolio to change the standards of care across pancreatic, lung, and colorectal cancers.

我們正按計畫推進，將於 2026 年第一季啟動首次人體試驗。基於我們在三個臨床階段資產方面取得的進展，我們對 RAS(ON) 抑制劑產品組合改變胰臟癌、肺癌和大腸直腸癌治療標準的潛力充滿信心。

We also have several discovery and clinical collaborations designed to expand the range of treatment strategies we can bring to bear for patients with RAS-addicted cancers. These collaborations enable us to explore diverse combinations of our RAS(ON) inhibitors with inhibitors of novel disease targets, including ovoprimetastat, a PRMT5 inhibitor under our agreement with Tango Therapeutics and ivonescimab, a bispecific PD-1 VGF inhibitor under our agreement with Summit Therapeutics.

我們也進行了多項探索和臨床合作，旨在擴大我們能夠為 RAS 成癮性癌症患者提供的治療策略範圍。這些合作使我們能夠探索 RAS(ON) 抑制劑與新型疾病標靶抑制劑的各種組合，包括根據我們與 Tango Therapeutics 的協議開發的 PRMT5 抑制劑 ovoprimetastat，以及根據我們與 Summit Therapeutics 的協議開發的雙特異性 PD-1 VGF 抑制劑 ivonescimab。

With our rich promising clinical and preclinical pipeline, we continue making investments to scale our organization to meet the extraordinary range of opportunities that affords. In support of this work, we've made new key appointments across late-stage functions.

憑藉我們豐富且前景廣闊的臨床和臨床前研發管線，我們將繼續投資擴大組織規模，以掌握由此帶來的巨大機會。為了支持這項工作，我們在後期階段的關鍵職能部門進行了新的任命。

In our R&D organization, we announced that Dr. Alan Sandler joined RevMed as our new Chief Development Officer. As an accomplished leader in oncology with a strong track record in cancer drug development, Alan brings valuable insights and expertise to our organization.

在我們的研發部門，我們宣布艾倫桑德勒博士加入 RevMed，擔任新的首席開發長。作為一位在腫瘤學領域卓有成就的領導者，Alan 在癌症藥物研發方面擁有卓越的成就，為我們組織帶來了寶貴的見解和專業知識。

We likewise expanded and strengthened our global and regional commercialization capabilities with additional appointments across our commercialization functions, including two key regional leaders. Alicia Gardner was appointed Senior Vice President and General Manager of the US region, and Gerwin Winter, recently joined RevMed as Senior Vice President and General Manager of the European region.

同時，我們透過在商業化職能部門增派人手，擴大和加強了全球和區域商業化能力，其中包括兩位重要的區域領導人。Alicia Gardner 被任命為美國地區高級副總裁兼總經理，而 Gerwin Winter 最近加入 RevMed 擔任歐洲地區高級副總裁兼總經理。

I'd now like to turn the call over to Jack Anders to summarize our third quarter financial results.

現在我把電話交給傑克·安德斯，讓他總結一下我們第三季的財務表現。

Thanks, Mark. We ended the third quarter of 2025 with $1.93 billion in cash and investments. This balance includes the receipt of the first royalty monetization tranche of $250 million in June 2025 from our partnership with Royalty Pharma, and there remains an additional $1.75 billion in future committed capital under this arrangement.

謝謝你，馬克。截至 2025 年第三季末，我們擁有 19.3 億美元的現金和投資。餘額包括 2025 年 6 月從我們與 Royalty Pharma 的合作中收到的第一筆 2.5 億美元的特許權使用費貨幣化款項，根據該安排，未來還有 17.5 億美元的承諾資本。

Turning to expenses. R&D expenses for the third quarter of 2025 were $262.5 million compared to $151.8 million for the third quarter of 2024.

接下來談談費用。2025 年第三季的研發費用為 2.625 億美元，而 2024 年第三季的研發費用為 1.518 億美元。

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 ongoing Phase 3 trials. Personnel-related expenses and stock-based compensation expense also increased in 2025 due to additional headcount.

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生產費用的增加，其中 daraxonrasib 是增加費用的最大驅動因素，因為其正在進行 3 期試驗。由於員工人數增加，2025 年人事相關費用和股票選擇權費用也有所增加。

G&A expenses for the third quarter of 2025 were $52.8 million compared to $24.0 million for the third quarter of 2024. The increase in G&A expenses was primarily due to increases in personnel-related expenses and stock-based compensation expense associated with additional headcount, increased commercial preparation activities, and increased legal expenses.

2025 年第三季的一般及行政費用為 5,280 萬美元，而 2024 年第三季為 2,400 萬美元。一般及行政費用的增加主要是由於人員增加、商業準備活動增加以及法律費用增加導致的人員相關費用和股票選擇權費用增加。

Net loss for the third quarter of 2025 was $305.2 million compared to $156.3 million for the third quarter of 2024. The increase in net loss was primarily driven by higher operating expenses.

2025 年第三季淨虧損為 3.052 億美元，而 2024 年第三季淨虧損為 1.563 億美元。淨虧損增加主要是因為營運費用增加所致。

We are reiterating our 2025 financial guidance and expect projected full year 2025 GAAP net loss to be between $1.03 billion and $1.09 billion, which includes estimated noncash stock-based compensation expense of of between $115 million and $130 million.

我們重申 2025 年財務預期，預計 2025 年全年 GAAP 淨虧損將在 10.3 億美元至 10.9 億美元之間，其中包括預計 1.15 億美元至 1.3 億美元的非現金股票選擇權費用。

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

財務更新到此結束。現在我將把通話轉回給馬克。

Thank you, Jack. We are highly encouraged by continuing momentum as we seek to build a leading global targeted medicines franchise for patients living with RAS-addicted cancers. We believe our strong financial position expansive development plans for our compelling pipeline assets and global commercialization ambitions will allow us to establish new global standards of care. We've made great progress across our pancreatic and lung cancer clinical programs and continue to generate encouraging data that informs our plans in colorectal cancer.

謝謝你，傑克。我們致力於為 RAS 成癮癌症患者打造全球領先的標靶藥物產品線，並為此感到倍受鼓舞，因為我們正朝著持續發展的目標邁進。我們相信，憑藉我們雄厚的財務實力、極具吸引力的在研資產的宏偉發展計劃以及全球商業化雄心，我們將能夠建立新的全球護理標準。我們在胰臟癌和肺癌臨床計畫方面取得了巨大進展，並持續產生令人鼓舞的數據，這些數據為我們制定結直腸癌計畫提供了依據。

Underpinning the passion and drive at RevMed is our collective commitment to patients. November is recognized globally as both pancreatic cancer awareness month and lung cancer awareness month, which align with two highly visible cornerstones of the clinical development efforts by our organization. We have expanded our partnerships with the advocacy community to better understand the dynamics that affected patients experience with RAS-driven cancers. Insights from these engagements will continue supporting our development of patient-friendly clinical protocols, access solutions, and educational initiatives.

RevMed 的熱情和動力源自於我們對病人的共同承諾。11 月是全球公認的胰腺癌宣傳月和肺癌宣傳月，這與我們組織臨床開發工作的兩個非常引人注目的基石相吻合。我們擴大了與倡導團體的合作，以便更好地了解影響 RAS 驅動型癌症患者體驗的各種因素。從這些交流中獲得的見解將繼續支持我們制定對患者友善的臨床方案、獲取途徑和開展教育計劃。

We hope you will join us in supporting the high-impact work by advocacy organizations as they seek to improve outcomes for patients through educational resources, support and research.

我們希望您能加入我們，支持倡導組織進行的高影響力工作，他們致力於透過教育資源、支持和研究來改善患者的治療效果。

Before closing, I'd like to acknowledge the continued support of our patients and caregivers, clinical investigators, scientific and business collaborators, advisers, shareholders, and importantly, the remarkable team of revolutionaries who drive exciting steps forward on behalf of patients.

在結束演講之前，我要感謝我們的患者和護理人員、臨床研究人員、科學和商業合作夥伴、顧問、股東，以及非常重要的，推動患者取得激動人心進展的傑出革命團隊的持續支持。

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

我們的演講到此結束，現在我將把電話交給接線生進行問答環節。

(Operator Instructions) Jonathan Chang, Leerink Partners.

（操作說明）Jonathan Chang，Leerink Partners。

Hi, guys. Thanks for taking my question. How are you thinking about the impact of receiving the commissioner's national priority voucher on daraxonrasib timelines and your plans?

嗨，大家好。謝謝您回答我的問題。您認為獲得專員的國家優先券會對 daraxonrasib 的時間表和您的計劃產生什麼影響？

Jonathan, thanks for your question. Well, obviously, we're very proud to have received one of the first nine vouchers. Actually, it's the only oncology product that's featured in that particular set. The stated goal of that voucher program, the pilot program is to accelerate the review time lines by some significant amount potentially making the review time line short just one to two months, and we'll do everything we can to support that.

喬納森，謝謝你的提問。當然，我們非常自豪能夠獲得首批九張優惠券之一。事實上，它是該系列產品中唯一一款腫瘤治療產品。此代金券計畫（試點計畫）的既定目標是大幅加快審核時間，有可能將審核時間縮短至一到兩個月，我們將盡一切努力支持這個目標。

But we've been aggressively preparing for the data readouts and then an expected submission of an NDA, and to be ready at the earliest possible time for launching a product. I don't think at this point in time, we anticipate that we would have any difficulty meeting whatever timeline might be delivered under the CNBB process.

但我們一直在積極準備資料讀取，然後預計提交保密協議，以便儘早推出產品。我認為目前來看，我們預期在 CNBB 流程下，無論時間節點為何，我們都不會遇到任何困難。

Understood. Thanks for taking my question.

明白了。謝謝您回答我的問題。

Charles Zhu of LifeSci Capital.

LifeSci Capital 的 Charles Zhu。

Hello, good afternoon, slash, good evening. Thanks for taking my question. Congrats on the progress. I've got a couple regarding RASolute 304, the adjuvant daraxonrasib trial. This might be a little naive, but can you help us understand and perhaps educate us on the decision to randomize against observation in perioperative chemotherapies setting?

你好，下午好，/晚上好。謝謝您回答我的問題。恭喜你取得進展。我有一些關於 RASolute 304 和輔助 daraxonrasib 試驗的問題。這可能有點天真，但您能否幫助我們理解並或許可以教育我們一下在圍手術期化療中隨機分組與觀察分組的決定？

And is there, I guess, clinical value in, maybe at some point, evaluating whether or not one could displace chemotherapy in this particular disease setting as well? Can you also help talk about -- help us understand and talk about the requirement for at least four months of perioperative chemotherapy as an eligibility criteria prior to randomizing against the two arms? Thank you.

那麼，我想，在某種特定疾病情況下，評估是否也能以藥物取代化療，是否具有臨床價值？您能否也幫助我們理解並討論一下，在隨機分組到兩個治療組之前，至少需要接受四個月的圍手術期化療這一入選標準？謝謝。

Thanks a lot, Charles, for your question. I think Dr. Sandler would be happy to comment on the rest of the RASolute 304 trial.

查爾斯，非常感謝你的提問。我認為桑德勒博士很樂意對 RASolute 304 試驗的其餘部分發表評論。

Great. Thanks. Sounds like it's a three-part question, and hopefully, I'll remember all three parts. So the aspect of -- I'll start with the four months of therapy, that's considered to be the standard of care that's been established previously. And so we wanted to add to that. So we're requiring that patients received standard of care therapy.

偉大的。謝謝。聽起來像是一個包含三個部分的問題，希望我能記住所有三個部分。所以，關於治療方面——我先從四個月的治療說起，這被認為是之前確立的標準治療方案。因此，我們希望在此基礎上有所貢獻。因此，我們要求患者接受標準治療。

And for that, and that's at least four months of therapy. So that's number one. Then the idea is to randomize patients to no further treatment or two years of additional adjuvant therapy with daraxon.

為此，至少需要四個月的治療。這是第一點。然後，將患者隨機分為兩組：一組不接受進一步治療，另一組接受為期兩年的達拉松輔助治療。

And the idea then is to build upon the success that has been seen modest but success that has been seen with chemotherapy in this setting. And so this, I think, offers the best approach to patients with resectable pancreatic cancer.

因此，我們的想法是在此基礎上，進一步鞏固化療在這種環境下所取得的雖不顯著但有效的成果。因此，我認為這是治療可切除胰臟癌患者的最佳方法。

Your last question, I think, was to potentially replace chemotherapy. And I think based on what we see from the adjuvant study, we'll reassess a plan accordingly. But I think we're very excited about this particular opportunity already and are looking forward to initiating the trial.

我想，你最後一個問題是關於是否有可能取代化療。我認為，根據輔助治療研究的結果，我們將相應地重新評估治療方案。但我認為我們已經對這個機會感到非常興奮，並期待著開始試驗。

Excellent. Thank you very much for taking my question. And congrats on the progress.

出色的。非常感謝您回答我的問題。恭喜你的進展。

Michael Schmidt of Guggenheim.

古根漢美術館的麥可·施密特。

Hey. Thanks for taking my question. Congrats on all the progress. A couple of questions on PDAC. So as we think about RASolute 302, how would you expect results from the Phase 2 study to translate to the large global Phase 3 study? Are there any anticipated differences, for example, in patient characteristics when you go from a smaller Phase 2 to a large global study?

嘿。謝謝您回答我的問題。祝賀你們取得的所有進展。關於胰腺導管腺癌（PDAC）有幾個問題。那麼，當我們考慮 RASolute 302 時，您認為 2 期研究的結果將如何轉化為大規模的全球 3 期研究？從規模較小的 2 期臨床試驗過渡到規模較大的全球性研究時，患者特徵方面是否存在預期差異？

And secondly, I guess, in anticipation of positive data next year, how are you tracking towards commercial readiness in terms of CMC, manufacturing capacity, and then ramping up commercial infrastructure? Thanks so much.

其次，我想，考慮到明年可能會有積極的數據，你們在CMC、生產能力以及商業基礎建設方面，商業化準備工作進展如何？非常感謝。

Thanks, Michael. Appreciate the questions. Maybe Dr. Lin can first comment on the Phase 3 versus Phase 1/2 question.

謝謝你，麥可。感謝提問。或許林博士可以先就第三階段與第一/二階段的問題發表一下看法。

Thanks for the question. So it's certainly an important question that we thought very deeply before initiating Phase 3. So we look extensively at the patient's road in the Phase 1 cohort compared to the Phase 3 randomized studies that have been reported historically. I think our population since fairly similar in looking at all the baseline characteristics that are prognostic or predictive of response to either chemotherapy or one therapy.

謝謝你的提問。所以這確實是一個重要的問題，我們在啟動第三階段之前對此進行了非常深入的思考。因此，我們將對 1 期隊列中的患者歷程與以往報告的 3 期隨機研究進行比較，並進行深入研究。我認為，從所有能夠預示或預測化療或單一療法療效的基線特徵來看，我們的族群已經相當相似了。

There's a -- almost all the metrics are either comparable or in some measures, the historical Phase 3s were actually a little worse. So I think we do have a patient population in the Phase 1 setting that's fairly representative, of what we expect to enroll on the Phase 3. And furthermore, the RASolute 302 is a global study, the predominant enrollment will occur in the US with representing enrollment in Europe and in Japan. And therefore, another reason why we feel that the population on the Phase I will translate into the Phase 3.

幾乎所有指標都具有可比性，或者在某些方面，歷史上的第三階段實際上會更糟一些。所以我認為，我們在第一階段的患者群體與我們預期在第三階段招募的患者群體具有相當的代表性。此外，RASolute 302 是一項全球性研究，主要入組將在美國進行，歐洲和日本也會有一定比例的入組。因此，我們認為第一階段的人口數量將轉化為第三階段的人口數量，這也是另一個原因。

So -- and then finally, look historically, the trial for, there's a dereconsistency over a period of a decade or two all the Phase 3 trial delivering very, very similar performances with the chemotherapy. Again, I think we expect the performance certainly on the control arm will perform historically similar. So all these give us a large measure of reassurance that we can replicate to a large net measure because the patient population as well as the performance of the treatment historically are operating representation.

所以——最後，從歷史角度來看，在過去一二十年的時間裡，所有 3 期試驗都表現出非常非常相似的化療效果，結果並不一致。我再次認為，我們預期控制臂的性能肯定會與以往類似。因此，所有這些都讓我們有相當大的信心，我們可以將其複製到較大的淨規模，因為患者群體以及治療的歷史表現都具有實際代表性。

And then the question regarding commercial readiness, maybe I'll answer a comment part of it and then Anthony Mancini can comment on the other part.

至於商業準備方面的問題，也許我會回答一部分，然後安東尼·曼奇尼可以評論另一部分。

With regard to manufacturing, we have a very strong organization and supply chain that's really been prepared over the last number of years. We're already scaling at the proper level to be able to support whatever level of uptake there might be should we be able to launch a product. So I think we're in a very strong position there and don't anticipate anything that could pose a significant problem for us.

在生產製造方面，我們擁有非常強大的組織和供應鏈，這是過去幾年精心準備的。我們目前的規模已經達到了適當的水平，足以應對產品上市後可能出現的任何市場需求。所以我認為我們在這方面處於非常有利的地位，預計不會有任何事情會為我們帶來重大問題。

With regard to commercialization readiness beyond that, maybe Anthony can comment.

至於商業化準備方面，或許安東尼可以發表一些看法。

Yes. Thanks, Mark, and thanks, Michael, for the question. We're really pleased with how our launch readiness plans are advancing. We've -- as was outlined earlier, we now have experienced and talented executives leading our commercialization team, including now building into the region. So across multiple functions, including medical affairs, market access, marketing and sales. And we're deeply engaged in market-shaping activities and planning and KOL and advocacy organization engagement and building broader organizational capabilities around launch readiness.

是的。謝謝馬克，也謝謝麥可的提問。我們對產品發布準備計畫的進度非常滿意。正如之前概述的那樣，我們現在擁有經驗豐富、才華橫溢的高管來領導我們的商業化團隊，包括正在該地區開展業務。因此，涉及多個職能部門，包括醫學事務、市場准入、行銷和銷售。我們積極參與市場塑造活動和規劃，與關鍵意見領袖和倡議組織互動，並圍繞產品上市準備工作建立更廣泛的組織能力。

We continue to add highly experienced and talented team members as we advance our organizational launch readiness, including US field-based teams, and we're making great progress there. And we're confident in our ability to continue to attract the right talent with the right experience and capabilities, which is a key success factor for a successful launch, and we're confident that we can do that.

隨著我們組織啟動準備工作的推進，我們不斷吸收經驗豐富、才華橫溢的團隊成員，包括美國實地團隊，我們在這方面取得了巨大進展。我們有信心持續吸引具備合適經驗和能力的合適人才，這是成功推出產品的關鍵因素，我們有信心能夠做到這一點。

Andrea Newkirk, Goldman Sachs.

安德里亞·紐柯克，高盛集團。

Hi, team. Thank you for taking my question. This is Morgan on for Andrea. Based on the initial frontline metastatic PDAC data, how do you think about the efficacy of combination treatment relative to monotherapy, rather greater time on treatment could increase the delta on ORR and DCR?

大家好。感謝您回答我的問題。這裡是摩根替安德里亞報道。根據初步的第一線轉移性 PDAC 數據，您如何看待聯合治療相對於單藥治療的療效？延長治療時間是否可以提高 ORR 和 DCR 的差異？

And then with regard to updated daraxonrasib monotherapy and combination data in the first half of next year, in frontline metastatic PDAC, how should we be thinking about durability? Thank you so much.

那麼，關於明年上半年更新的達拉西單藥治療和合併治療數據，在轉移性胰臟癌第一線治療中，我們該如何看待其持久性？太感謝了。

Thanks for the question, Morgan. Wei, would you like to comment on those -- the first question being the difference -- what level of difference is there between monotherapy versus combination and will that clarify over time?

謝謝你的提問，摩根。魏，你能否就這些問題發表一下看法——第一個問題是區別——單藥治療與聯合治療之間究竟存在多大程度的區別，隨著時間的推移，這種區別會更加清晰嗎？

Yeah. So the monotherapy versus combination in frontline, I think as discussed previously, really test two very distinct hypotheses. I think one is really the sequential treatment by introducing additional line of therapy, because currently stand of care, only two lines of effect therapy are exist for patients at an based and a five-view based.

是的。因此，我認為正如之前討論的那樣，一線單藥治療與聯合治療實際上是在檢驗兩個截然不同的假設。我認為一種方法是透過引入額外的治療方案來進行序貫治療，因為目前，對於基於一個治療方案和基於五種治療方案的患者來說，只有兩種有效的治療方案。

And by using daraxonrasib monotherapy, we used a third monotherapy. And could that introduction a third-line therapy with very promising data in the second-line setting translate to [long issue overall] survival. And then the other chemo combination are -- really tests very distinct hypothesis, which is a potential synergy by combining thw two, those patients still get two lines of therapy.

透過使用達拉西單藥療法，我們使用了第三種單藥療法。那麼，這種在二線治療中數據非常有希望的三線療法能否轉化為[長期總體]生存期呢？而另一種化療組合——實際上是在檢驗一個非常獨特的假設，即兩種藥物結合可能產生的協同作用，這些患者仍然接受兩線治療。

But then the first line therapy is actually a combination regimen of a RAS inhibitor plus center extending the progression survival that can also translate to on overall survival. So I think these hopefully will translate into surviving benefit, as well as different options for patients who get tolerated a more potent regimen versus who are seeking better quality of life and for the -- that provides by monotherapy.

但一線治療其實是 RAS 抑制劑合併治療方案，可以延長疾病惡化存活期，這也可以轉化為總存活期。所以我認為這些有望轉化為生存獲益，並為能夠耐受更強效治療方案的患者提供不同的選擇，同時也為那些尋求更高生活品質的患者提供單藥治療方案。

And just to add to that, of course, there's really no way to answer the question about how those two regimens compare, except to test them both. And they're both very credible in the meaty scientific hypothesis.

當然，除此之外，要回答這兩種療法孰優孰劣這個問題，唯一的方法就是對它們進行測試。而且，他們在實質的科學假設方面都非常可信。

The second question, I think, had to do with what sort of update can be expected next year with regards to the durability of the effect that we have already reported. We do intend to provide an update in the first half of 2026.

我認為第二個問題與明年可以預期獲得關於我們已經報告的效果的持久性方面的更新有關。我們計劃在 2026 年上半年提供最新進展報告。

Okay, thank you.

好的，謝謝。

Brian Cheng, JPMorgan.

Brian Cheng，摩根大通。

Hey, guys. Thank you for taking my question this afternoon. Just first on your voucher. What additional pieces of information have you learned on the use of it, since you received it in mid-October?

嘿，夥計們。感謝您今天下午回答我的問題。就在您的憑證上。自 10 月中旬收到該產品以來，您還了解到了哪些關於其使用方面的其他資訊？

Specifically, do we know which line of setting the vouchers for since the language in the press release seems to be more broadly applicable to a PDAC? And then we have a follow-up. Thank you.

具體來說，我們是否知道為哪一行設定代金券，因為新聞稿中的措辭似乎更廣泛地適用於 PDAC？然後我們還有後續報道。謝謝。

Yeah. Thanks for your question, Brian. We don't really have any additional information to share with you today. We are certainly in ongoing dialogue with the FDA and learning more about how this voucher system will work and what impact it might have on how we approach preparing an NDA, but no other comments available today.

是的。謝謝你的提問，布萊恩。今天我們沒有其他資訊可以跟大家分享。我們當然正在與FDA進行持續對話，並了解更多關於該代金券制度如何運作以及它可能對我們準備NDA的方式產生何種影響的信息，但今天沒有其他評論。

Okay. And then just quickly on Sodon's combo Phase III fund line PDAC now that you have 303 on track to start later this year. I'm just curious if you can talk a little bit about just some consideration that you currently have when it comes to the selection of the doublet versus triplet, and I think also the active comparative piece, how should we think about which active comparator arm you should put in to make it -- make sure that physicians understand how they look at soon combo in the future?

好的。然後，簡單談談 Sodon 的三期組合基金 PDAC，因為你們的 303 項目已經按計劃將於今年晚些時候啟動。我只是好奇您能否談談目前在選擇雙聯療法還是三聯療法時的一些考慮因素，以及我認為在活性對照方面，我們應該如何考慮應該加入哪個活性對照組，以確保醫生們了解他們將來如何看待聯合療法？

Yeah, that's a great question, and it perfectly tees up when we present some information about that, we'll be able to address all of those questions. But I assure you, we will comment on all of that. Maybe the big picture right now is just that we are taking multiple approaches to treating this devastating disease. And we're in the second or third inning of this battle.

是的，這是一個很好的問題，當我們提供一些相關資訊時，我們就能很好地回答所有這些問題了。但我向你保證，我們會對所有這些問題作出回應。或許目前最值得關注的是，我們正在採取多種方法來治療這種毀滅性的疾病。我們現在正處於這場戰鬥的第二局或第三局。

And we're going to keep investing in it until we've really moved the needle as much as we possibly can. So we're excited to bring that approach forward, and we'll give you more color about it when we are able to lay that out much more explicitly.

我們將繼續投入資金，直到我們盡可能地取得實質進展。所以我們很高興能提出這個方法，等我們能夠更明確地闡述之後，會再向大家詳細介紹。

Great. Thank you.

偉大的。謝謝。

Marc Frahm, TD Cowen.

馬克·弗拉姆，TD Cowen。

Thanks for taking my question. Congrats on all the progress. Maybe just sort of on that zoldonrasib first-line trial. Just the idea of only pursuing combinations. I guess, should we read into that the monotherapy maybe doesn't seem as durable as daraxonrasib as a monotherapy since you were interested in pushing forward the monotherapy in first line in that setting? And then I'd like we have a follow-up.

謝謝您回答我的問題。祝賀你們取得的所有進展。或許只是參與了zoldonrasib一線治療試驗。只是追求組合的想法。我想，既然您有興趣在這種情況下將單藥療法作為一線療法來推進，那麼我們是否應該理解為單藥療法的持久性可能不如達拉西布單藥療法？然後我希望我們能進行後續跟進。

Thanks, Mark. I'm not sure about that last comment. I'm not sure that we ever gave any inclination with regard to zoldonrasib in first line and what sort of strategies we might pursue. So I don't think we need to explain something that I don't think we ever committed to.

謝謝你，馬克。我不太確定最後那句話的意思。我不確定我們是否曾就一線治療方案中的 zoldonrasib 以及我們可能採取的策略給出任何建議。所以我覺得我們沒必要解釋一些我們從未承諾過的事情。

Daraxonrasib alone, we're setting in first line as monotherapy. We're going to learn a lot from that study. And zoldonrasib is an ideal combination agent because of its pretty remarkable safety and tolerability profile. So it is a real opportunity to see how far we can push things.

Daraxonrasib 單獨使用，我們將其作為一線單藥療法。我們將從這項研究中學到很多。由於其安全性和耐受性都非常出色，zoldonrasib 是一種理想的聯合用藥。所以這是一個真正檢驗我們能把事情推向何種程度的機會。

And in terms of further differentiating options for patients, we will certainly continue to be committed to that. So I don't think you should infer anything from that decision and that strategy, other than we're looking for the best possible ways to deliver impact for patients that would complement the other options that are coming out of our portfolio.

至於為患者提供更多差異化選擇，我們肯定會繼續致力於此。所以我認為你不應該從這項決定和策略中推斷出任何事情，除了我們正在尋找能夠為患者帶來最佳影響的方式，以補充我們產品組合中其他可供選擇的方案。

Okay. That's helpful. And then on 302, now that you're getting pretty close to the end of enrollment, can you maybe speak to kind of how the event rate has been trending maybe relative to kind of how you guys were projecting it when you designed the trial?

好的。那很有幫助。那麼，關於 302，現在你們的招募工作已經接近尾聲了，能否談談事件發生率的趨勢，以及與你們在設計試驗時所預測的相比如何？

And then as the interim start to get taken, just what's the latest thoughts on disclosure strategy will you inform investors whenever an interim is taken or whatever the result of that was, or likely only speak if the interim results in some sort of stoppage of the trial?

然後，隨著中期審查的開始，關於資訊揭露策略的最新想法是什麼？您會在每次進行中期審查或審查結果公佈時都告知投資者嗎？還是可能只有在中期審查導致審判某種程度的中止時才會公佈？

And personally, Marc, I think you're open to on those questions. Anything to comment on either of those at this time.

馬克，就我個人而言，我認為你對這些問題持開放態度。目前對這兩件事都沒有什麼要評論的。

Great. Fair enough.

偉大的。很公平。

Leonid Timashev, RBC.

列昂尼德·蒂馬舍夫，RBC。

Thank you for taking my question. Just wanted to ask on sort of the commercial opportunity, I mean, given that you recently hired President of EU strategy. Just how you're thinking about the landscape in the European Union with respect to where patients lie in terms of commercial opportunity, the concentration there, awareness, diagnostic opportunities? Just anything you can speak to to how you think the European strategy might take shape?

感謝您回答我的問題。我只是想問一下商業機會方面的問題，我的意思是，鑑於你們最近聘請了歐盟戰略總裁。您如何看待歐盟的患者群體在商業機會、集中度、認知度和診斷機會等方面的現況？您能否談談您對歐洲戰略可能如何形成的看法？

Thank you. I appreciate that question. It's a gigantic question. So I'm immediately going to ask Anthony to address. (laughter)

謝謝。感謝你的提問。這是一個巨大的問題。所以我馬上要請安東尼發言。（笑聲）

No. Look, it's -- there's been a lot of thought put into how we're thinking about bringing daraxonrasib patients. Clearly, different from many companies' opportunities with a first launch and a first indication. We think the second-line pancreatic cancer indication is a meaningful one -- so you can look at the in the key European markets, starting with Germany and the EU, for and beyond, and there are many patients to treat. We think that will bring a compelling value proposition in Europe.

不。你看，我們已經認真思考過如何讓達拉西布患者接受治療。顯然，這與許多公司在首次推出和首次亮相時所面臨的機會截然不同。我們認為二線胰臟癌適應症是一個有意義的適應症——因此，你可以看看歐洲主要市場，從德國和歐盟開始，甚至更遠的地方，那裡有很多患者需要治療。我們認為這將為歐洲市場帶來極具吸引力的價值主張。

And we think it's going to be a meaningful opportunity in Europe, in the US, and Japan. And so we're pursuing that. I think there's nothing more to comment on, except that those are our priority markets, and we intend to bring our best foot.

我們認為這將是歐洲、美國和日本的重要機會。所以我們正在努力實現這個目標。我覺得沒什麼好說的了，除了這些是我們優先發展的市場，我們會全力以赴。

Great, thank you.

太好了，謝謝。

Clara Don, Jefferies.

克拉拉唐，傑富瑞。

Hi. This is Jen on for Clara. Could you talk about if there were any rationale behind starting the adjuvant study before the first-line study?

你好。這裡是Jen替Clara報道。您能否談談在進行第一線治療研究之前先進行輔助治療研究的理由？

Jenna, thanks for your question. That's pretty straightforward. There's nothing profound underneath it. It's a simpler study, obviously, it's a single treatment arm and we're just able to get that up and running a little bit earlier, but I don't think it will materially differ in terms of the overall conduct of it, of course, that is going to be a longer study in terms of the readout given the time lines that we talked about. So it doesn't make much difference.

Jenna，謝謝你的提問。這很簡單。它背後並沒有什麼深刻的意義。顯然，這是一項更簡單的研究，它只有一個治療組，我們只是能夠提前一點啟動並運行它，但我認為就整體實施而言，它不會有實質性的不同。當然，考慮到我們討論的時間線，就結果公佈而言，這將是一項更長的研究。所以差別不大。

And it just happened that we were able to proceed with it.

碰巧我們能夠繼續進行下去。

Asthika Goonewardene, Truist Securities.

Asthika Goonewardene，Truist 證券公司。

Hi, guys. Thanks for taking my question. So you've described what resistance mechanisms emerged with daraxonrasib and PDAC. And you should have a considerable amount of data with daraxonrasib non-small cell lung cancer, two underhood. So I'm just wondering, do you expect non-small cell lung cancer to also follow a similar path of resistance as PDAC or are there any new resistance mechanisms that are emerging that you can tell us about? I'm wondering how this guided your choice of selecting pembro and chemo for the combination versus just a chemo-sparing pembro combo? And then I have a follow-up.

嗨，大家好。謝謝您回答我的問題。所以你已經描述了達拉西尼和 PDAC 中出現的抗藥性機制。你應該有相當多的關於達拉西布治療非小細胞肺癌的數據，這是兩個底層數據。所以我想知道，您是否認為非小細胞肺癌也會像胰臟導管腺癌一樣出現抗藥性？或者有任何新的抗藥性機制正在出現，您可以告訴我們？我想知道，您是如何決定選擇帕博利珠單抗合併化療，而不是只選擇不聯合化療的帕博利珠單抗合併化療方案的？然後我還有一個後續問題。

Thanks for your question. That's sort of a subtle comment at the end of that question. Maybe Dr. Kelsey can discuss resistance what we know about PDAC expectations across other tumor types? And how has that affected our thinking for trial stuff.

謝謝你的提問。這是對這個問題的一種微妙補充。凱爾西醫師或許可以跟我們探討一下，對於胰臟導管腺癌的抗藥性，我們目前對胰臟導管腺癌的了解是否適用於其他腫瘤類型？這又如何影響了我們對審判相關事宜的思考？

The data that we have on emerging mechanisms of resistance to daraxonrasib non-source lung cancer is probably not sufficiently mature for public disclosure at this stage. There are a number of confounding issues around that. The first is, as you know, we declared our recommended Phase 2 dose for nonsense lung cancer after we had declared the recommended last dose in pancreatic cancer. So the information that we would only really be important at the recommended Phase 2 dose.

我們目前掌握的 daraxonrasib 非來源肺癌抗藥性機制的數據可能還不夠成熟，不適合在現階段公開揭露。這其中存在著許多令人困惑的問題。如您所知，第一點是，在我們宣布了胰腺癌的建議最終劑量之後，我們宣布了無義肺癌的建議 2 期劑量。因此，我們掌握的資訊只有在建議的二期劑量下才真正重要。

The second is the number of people that actually have progressed and been documented to progress. And the third issue there are the number of patients with progression that actually has detect circulating ctDNA in order to make an assessment of whether there's anything to see. The other thing is that traditionally in non-small cell lung cancer, they appear to have been from the literature that's available a lot of resistance mechanisms that are possibly not even genomic.

第二點是實際取得進步並有記錄在案的進步人數。第三個問題是，有多少病情進展的患者實際上檢測到了循環 ctDNA，以便評估是否有任何異常發現。另一方面，傳統上，非小細胞肺癌似乎存在許多抗藥性機制，從現有文獻來看，這些機制甚至可能不是基因組層面的。

And so it's going to take a little bit more time to figure that out. And I think that all bets are off really mapping mechanisms of resistance in pancreatic cancer to mechanisms of resistance in non-small cell lung cancer. We already know that the biological resistance mechanisms and colorectal cancer, for instance, to G12C inhibitors are different from the biological resistance mechanisms to G12C inhibitors and non-sale lung cancer.

所以還需要一些時間來弄清楚這一點。我認為，將胰臟癌的抗藥性機制與非小細胞肺癌的抗藥性機制進行類比，目前還無法確定。我們已經知道，例如，G12C 抑制劑在結直腸癌中的生物抗藥性機制與 G12C 抑制劑在非肺癌中的生物抗藥性機制不同。

They are qualitatively similar and overlap but they're not, they're not identical. And I don't think that we can infer anything at this stage. With regards to how that information informs how we move forward with combinations, it really has no bearing on it.

它們性質相似且有重疊之處，但它們並不相同，它們並不完全一致。我認為現階段我們無法得出任何結論。至於這些資訊如何影響我們推進組合策略，它實際上沒有任何影響。

The selection of pembrolizumab as a partner for any of our RAS on inhibitors is driven really by two things. One, is the almost ubiquitous inclusion of pembrolizumab or an equivalent checkpoint inhibitor into the standard of care for non-small cell lung cancer. And the second is the increasingly compelling body of evidence that suppressing RAS does actually made pembrolizumab more effective because it profoundly changes the immune microenvironment for the and allow the immune system much more access to the tumor for a whole lot of reasons that we have published and a number of other groups have published.

選擇帕博利珠單抗作為我們任何 RAS 抑制劑的搭檔，主要受兩方面因素驅動。一是帕博利珠單抗或同等的檢查點抑制劑幾乎普遍被納入非小細胞肺癌的標準治療方案中。第二點是越來越多的有力證據表明，抑制 RAS 確實能使帕博利珠單抗更有效，因為它深刻地改變了免疫微環境，使免疫系統更容易接觸到腫瘤，這其中有很多原因我們已​​經發表過，其他一些研究小組也發表過。

So -- when we have the data, we will disclose it, and it may influence how we move forward, and it may not. There are really two separate issues there.

所以——當我們掌握數據後，我們會公佈數據，這可能會影響我們未來的行動，也可能不會。實際上，這裡涉及兩個不同的問題。

And then if I can just tag on to Charles' previous question. By requiring in the 304 study, by requiring patients to have four months of chemotherapy, does this help select out patients who are deemed to be borderline resectable?

然後，我可以補充一下查爾斯之前的問題嗎？304 研究要求患者接受四個月的化療，是否有助於篩選出被認為處於臨界可切除狀態的患者？

Yeah, Hi. I'll take that. No, the -- first, I'll talk about the purpose of it was, again, the four months of standard of care. The question about your border line and the readily resectable. What we've done is we've allow those patients to undergo the standard treatment that they would locally and whether they're surgically resected not. And then the only way they're able to enter on study is if they are pathologically completely resected either with totally clear or narrow margins, the RAS(ON) or R1 that was shown on the slide.

嗨。我接受。不，首先，我要談談它的目的，再次強調，是四個月的標準護理。關於你的界線和易於切除的問題。我們所做的就是允許這些患者接受與當地相同的標準治療，無論他們是否接受手術切除。而只有當腫瘤在病理學上被完全切除，且切緣完全乾淨或狹窄，即切片上顯示的 RAS(ON) 或 R1 時，他們才能參與研究。

And then those patients are then randomized to the treatment as such. It -- in a sense, it eliminates those patients who are not able to be resected, but it also allows those patients with the borderline resectable, an opportunity to receive adjuvant therapy if they're perioperative therapy and surgery was successful. So it broadens the number of patients who have access to this therapy in the study.

然後將這些患者隨機分配到相應的治療組。從某種意義上說，它排除了那些無法進行手術切除的患者，但也讓那些處於可切除邊緣的患者有機會接受輔助治療，前提是他們接受了圍手術期治療並且手術成功。因此，它擴大了研究中可接受這種療法的患者人數。

To also add one point about the question of why four months, there is a variety of different approaches that people take in treating that disease. They all center around using chemotherapy before, after or both before and after and by requiring a standardized duration of treatment, we can make the patient population more uniform and easier to compare the two groups to each other. And avoiding balances in their treatment regimens.

關於為什麼是四個月這個問題，我還要補充一點，因為人們在治療這種疾病時會採取各種不同的方法。它們都圍繞著在治療前、治療後或治療前治療後都使用化療展開，透過要求標準化的治療持續時間，我們可以使患者群體更加統一，更容易將兩組患者進行比較。並避免在治療方案中出現平衡問題。

All right. Thank you.

好的。謝謝。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

Hi, guys. Thanks for taking my question. And congrats on the updates. Two from us. First on zoldonrasib, Curious how you're thinking about the opportunity for zoldonrasib top of chemo versus daraxonrasib plus chemo and RASolute 303? Do you plan to enroll similar patients in both studies or maybe try to subset the frontline opportunity?

嗨，大家好。謝謝您回答我的問題。恭喜您收到更新通知。我們兩人都同意。首先，關於zoldonrasib，我很好奇您如何看待在化療基礎上加用zoldonrasib與daraxonrasib聯合化療和RASolute 303的療效對比？您計劃在兩項研究中招募相似的患者，還是嘗試篩選第一線治療對象？

And secondly, how important is the RAS doublet in terms of your ideal commercial strategy longer term, specifically thinking about zoldonrasib in the front-line PDAC?

其次，從長遠來看，RAS 雙聯體在您理想的商業策略中有多重要？特別是考慮到第一線 PDAC 治療中的 zoldonrasib 而言？

Okay. Maybe I can just comment on the second one and then maybe Wei can comment can address your first question. So with regard to RAS inhibitor doublets, we still have high conviction about it. We just showed some data on zoldonrasib plus daraxonrasib in preclinical models just last month at the triple meeting. And we're we feel like it's a compelling option.

好的。或許我可以先評論第二個問題，然後魏可以評論並回答你的第一個問題。所以對於 RAS 抑制劑雙藥組，我們仍然充滿信心。就在上個月的三方會議上，我們剛剛展示了一些關於 zoldonrasib 加 daraxonrasib 在臨床前模型中的數據。我們覺得這是一個很有吸引力的選擇。

Just stay tuned as we roll out the various studies that will be coming in the future. I think we have high interest in that.

請關注，我們將陸續推出各項研究。我認為我們對此非常感興趣。

The first question, I think, had to do with zoldon versus daraxon each in a first-line population and are we selecting patients differently between those. Obviously, one is all RAS mutations and the other is just KRAS G12D mutations. So there's that difference between them, but are there any other differences.

我認為第一個問題與第一線治療族群中 zoldon 與 daraxon 的比較有關，以及我們在選擇患者時是否採用了不同的方法。顯然，一種是全部 RAS 突變，另一種只是 KRAS G12D 突變。所以它們之間有這種區別，但還有其他區別嗎？

Wei?

魏？

Clinically, the liability otherwise are no different. And I think in the Phase 1 setting when we're doing the combination with the chemotherapy, it's truly the ability -- are really mainly decided to make adequate organ function out to deliver a chemotherapy. So we are actually also very, very similar.

從臨床角度來看，其他方面的責任並無不同。我認為在第 1 期臨床試驗中，當我們進行化療合併治療時，真正的關鍵在於能否使器官功能足以輸送化療藥物。所以，我們其實也非常非常相似。

[Joe Kevin Zaro, Mizuho.]

[喬·凱文·扎羅，瑞穗。 ]

Just maybe one quick one from me. As it relates to CRC, just wondering if there are any sort of key data points you are looking towards before maybe committing to earlier line later-stage trials and whether we should expect any of those data points in 2026? Thanks.

我可能只是簡單提一句。關於 CRC，我想知道在決定是否開展早期或後期試驗之前，您是否專注於任何關鍵數據點？我們是否可以預期在 2026 年獲得這些數據點？謝謝。

Thanks for your question. Thanks for joining us.

謝謝你的提問。謝謝您的參與。

Steve, do you want to comment on CRC?

史蒂夫，你想對CRC發表一下看法嗎？

Yeah, I'm happy to do that. I'm not going to comment on timing because we haven't really guided to data disclosure with regards to colorectal cancer. But I think we have previously made it pretty clear that due to the biological complexity of rapid and colorectal cancer, we believe that combination therapy is absolutely essential.

是的，我很樂意這樣做。我不會對時間安排發表評論，因為我們還沒有真正就結直腸癌的數據披露問題給出指導。但我認為我們之前已經非常明確地表明，由於快速進展型大腸直腸癌的生物學複雜性，我們認為聯合療法是絕對必要的。

In order to maximize clinical benefit and the studies that are designed to figure out which combinations are most efficacious in that context are currently ongoing. And so as soon as we figured it out, then we can both a path forward. We also don't forget that we have the -- there are several dimensions to this issue.

為了最大限度地發揮臨床療效，目前正在進行旨在確定哪些組合最有效的研究。所以一旦我們弄清楚了這一點，我們雙方就能找到前進的方向。我們也不會忘記，這個問題涉及多個層面。

I mean you mentioned one of them, which is line of therapy, whether or not we, Brian, go into the first-line status setting or whether we just tackle patients in the third and fourth line who are essentially being salvaged after chemotherapies failed. There are several different biologically rational combinations, including combinations with our own -- within our own portfolio, RAS(ON) doublets.

我的意思是，你提到了其中一個問題，那就是治療方案，布萊恩，我們是否應該進入一線治療階段，還是應該只針對三線和四線治療的患者，這些患者在化療失敗後基本上是需要挽救的。有幾種不同的生物學合理組合，包括與我們自己的組合－在我們自己的產品組合中，RAS(ON) 雙體。

And so we just need the opportunity to figure that out. It's a very complex -- colorectal cancer very complex disease. It's not entirely clear that RAS-mutant -- RAS is the only driver, the only oncogenic driver even in situations where it's actually mutated. So we've got -- we just sort of to happen.

所以，我們只需要一個機會來弄清楚這一點。大腸直腸癌是一種非常複雜的疾病。RAS 突變並不完全清楚——即使在 RAS 實際發生突變的情況下，RAS 也是唯一驅動因素，是唯一的致癌驅動因素。所以，我們──我們就這樣順其自然了。

Sean McCutcheon, Raymond James.

Sean McCutcheon，Raymond James。

This is Yang on for Sean. We have two quick ones. First one, regarding the first-line zoldonrasib what kind of threshold for efficacy by looking at anticipating that you have the update for the front line? And also commenting on the daraxonrasib and elironrasib combination in the first-line NCLC?

這是楊替肖恩發言。我們有兩個簡短的問題。首先，關於第一線藥物唑登拉西布，在預期一線治療方案更新的情況下，療效閾值應該是多少？另外，您對達拉西布和依利龍西布合併用於第一線非癌性肺癌治療有何評價？

Thanks for your questions. Let me make sure I understand. The first question had to do with an update on first-line PDAC with direct assets.

謝謝你的提問。讓我確認一下我理解得是否正確。第一個問題與直接資產的一線 PDAC 的最新情況有關。

No, sorry. Yeah, that's a non-small cell lung cancer, frontline arose what's the threshold efficacy bar you're looking at?

不，抱歉。是的，那是非小細胞肺癌，第一線治療方案的療效閾值是多少？

Okay. So in lung cancer, since we indicated that we'll proceed with a trial, and we'll provide information later. Yeah. I mean, obviously, we look at standards of care and what we see in a single-arm trial versus standards of care, even though they're not immediately comparable since it's not randomized data. But we'll look at standard of care and see if we can improve upon that.

好的。所以，在肺癌方面，我們已經表示將進行試驗，稍後會提供相關資訊。是的。我的意思是，很顯然，我們會檢視護理標準，以及我們在單臂試驗中看到的情況與護理標準之間的差異，儘管由於數據並非隨機數據，因此它們不能立即進行比較。但我們會審視現有的醫療標準，看看能否在此基礎上進行改進。

We typically wouldn't provide guidance as to what we consider an acceptable improvement. That's something that's a complicated topic. And that's between us and the statistical analysis plan and the FDA and so on. So no pre-guidance to be able to offer you today on that.

我們通常不會就我們認為可接受的改進程度提供指導。這是一個複雜的話題。那是我們和統計分析計畫、FDA等等之間的事。所以今天我無法就此提供任何預先指引。

And your second question?

你的第二個問題是什麼？

Yes. The second question is related to the combination potential with your RAS and G12C elironrasib in first-line NCLC?

是的。第二個問題與 RAS 和 G12C elironrasib 第一線治療 NCLC 的合併應用潛力有關？

Okay. That's back to the RAS inhibitor doublet. And in this case, it's the doublet of elironrasib plus daraxonrasib and that, too, is a very interesting combination. I think I'd just reiterate that we are -- we believe that the combination of a mute selective inhibitor with the daraxon multi inhibitor provides potentially the benefits of both of those compounds as complementary and delivering the greatest impact, and we've now shown two clinical data sets that support that one in colorectal cancer and one in lung cancer.

好的。這就回到了 RAS 抑制劑雙藥組的問題。在這種情況下，它是 elironrasib 加 daraxonrasib 的雙藥組合，也是非常有趣的組合。我想重申一下，我們相信，將一種選擇性抑制劑與達拉鬆多標靶抑制劑結合使用，可以發揮這兩種化合物互補的優勢，從而產生最大的影響。我們現在已經展示了兩組臨床數據來支持這一觀點，一組是針對大腸癌的，另一組是針對肺癌的。

Both of which were directionally quite similar. As to how we prioritize that relative to other options, that's a very complex matrix of considerations. And don't have anything to be able to guide you too specifically today about that.

兩者方向非常相似。至於我們如何權衡利弊，確定其優先級，這涉及許多非常複雜的考慮因素。今天我在這方面沒有什麼具體的建議可以給你。

Laura Prendergast, Stifel.

Laura Prendergast，Stifel。

Hey, gusy. Congrats on the quarter. I was just curious if it's possible, any sort of accelerated approval pathway could be there for first-line PDAC, whether that's an early cut for the Phase 3 study or something or anything else? Also, how are you factoring daraxonrasib being approved in second line into how you're thinking about the statistics for OS in the first-line study?

嘿，夥計們。恭喜你本季取得佳績。我只是好奇是否有可能，對於第一線 PDAC 治療，是否存在某種加速審批途徑，例如提前進行 3 期研究或其他任何途徑？另外，您是如何將 daraxonrasib 獲批用於二線治療納入您對一線研究 OS 統計數據的考慮的？

Okay. Laura, thanks for your questions. Maybe I'll comment on the AA question and then maybe Wei comment on the ones -- no comment. That's basically -- that's always a question for the FDA. That's not so much of a question for us.

好的。勞拉，謝謝你的提問。也許我會對AA的問題發表評論，然後魏可能會對那些——不予置評——發表評論。這基本上——這始終是FDA需要回答的問題。對我們來說，這並不是什麼大問題。

And I think there's no doubt that the initial data that we showed were quite encouraging. And I'm sure they're viewed that way by many people with what the FDA how they view it in a formal sense and what they want to do with it would be the subject of future dialogue and so on, really nothing that we can say about that.

毫無疑問，我們展示的初步數據相當令人鼓舞。我相信很多人都會這樣看待這個問題，至於美國食品藥品監督管理局（FDA）如何正式看待這個問題，以及他們想如何處理這個問題，這將是未來討論的主題等等，我們對此真的無可奉告。

I would say, just generally speaking, we've had a pretty strong habit of focusing on full approval strategies, which I think has served us well with regard to PDAC for sure so far. We're not at the end game yet, but it seems to have made sense. And we'll continue to prioritize that.

總的來說，我認為我們一直以來都非常注重全面審批策略，到目前為止，我認為這在 PDAC 方面肯定對我們很有幫助。雖然還沒到最後階段，但看起來這樣做是合理的。我們將繼續把這件事放在首位。

There may be some situations in which an accelerated approval can make sense to get something to patients as early as possible and where we think it makes sense and the FDA. More importantly, things that make sense, then we could always welcome that opportunity.

在某些情況下，加速審批可能有助於儘早將藥物送到患者手中，我們認為這樣做是合理的，FDA 也持相同觀點。更重要的是，如果事情合情合理，我們總是會歡迎這樣的機會。

Yeah. Regarding the design is to take is of the frontline, given our sand-mine efforts and data, I think probably there are several years to maybe that question. So on the first there is we're still designing a fully powered randomized trial to enable restoration based on more survival.

是的。關於設計是否應該放在前線，鑑於我們在沙礦方面的努力和數據，我認為可能還需要幾年時間才能回答這個問題。所以，首先，我們仍在設計一項充分有效的隨機試驗，以實現基於更高存活率的恢復。

And from that regard, doesn't really impact the fact that we deliver more survival. We do intend to deliver over so in front line, even (inaudible) in the second line. I think the data thatwe have reviewed so far, I think give us further confidence about the monotherapy benefit, and therefore, give us confidence about the arm with molecule PS as a combination.

從這個角度來看，這並不會影響我們提高存活率的事實。我們確實打算在前線交付，甚至在第二線（聽不清楚）。我認為我們目前審查的數據進一步增強了我們對單藥治療益處的信心，因此也增強了我們對PS分子聯合治療方案的信心。

Therefore, we're actually fully evaluating and fuel powering both arms and dependent testing them. So that does affect in that that's the second layer. That's the second layer.

因此，我們實際上正在全面評估並為這兩個部門提供燃料動力，並對其進行相關測試。所以這確實會產生影響，因為那是第二層。這是第二層。

The third layer is, I think you may be hinting at a question we addressed previously, which is with the second approval in the US that may be impact on crossover and whether when you pack our design. It doesn't really impact our design per se.

第三層，我認為你可能是在暗示我們之前討論過的一個問題，那就是在美國的第二次批准可能會對跨界合作產生影響，以及當你打包我們的設計時是否會產生影響。它本身並不會對我們的設計產生實際影響。

Elena impacts our operational and our footprint, I think we'll certainly assigned the sites more on ex-US to minimize the impact of crossover due to the availability of daraxonrasib for segmentation in the US.

Elena 對我們的營運和業務範圍產生了影響，我認為我們肯定會將更多站點分配到美國以外的地區，以盡量減少因 daraxonrasib 在美國用於分割而造成的交叉影響。

Okay, thank you very much.

好的，非常感謝。

Ami Fadia, Needham.

阿米法迪亞，尼德姆。

Hi, good afternoon. Thanks for taking my quesiton. And \apologies if this has been asked already. I've been juggling some calls here.

您好，下午好。感謝您回答我的問題。如果這個問題之前已經有人問過了，我深感抱歉。我一直在忙著接電話。

So my question is regarding the acquired alterations post-daraxon monotherapy that was presented at the triple meeting. How do you see that potentially impacting the durability of response in first line? And where you're studying in combination with chemo, would you consider exploring combinations with other mechanisms at this stage? Thank you.

所以我的問題是關於在三方會議上提出的達拉西酮單藥治療後所獲得的改變。您認為這可能會對第一線反應的持久性產生怎樣的影響？在您目前研究的化療聯合療法中，您是否考慮在這個階段探索與其他機制的聯合療法？謝謝。

Thanks, Ami. I'm trying to get to the gist of that question. Would we consider combining daraxonrasib with other compounds that target other potential drivers that are resistance mechanisms, in order to increase (multiple speakers)?

謝謝你，Ami。我正在努力理解這個問題的要點。我們是否會考慮將達拉索拉西布與其他靶向潛在抗藥性機制的化合物聯合使用，以提高療效？（多位發言者）？

That's right.

這是正確的。

Sure. We're already considering and we're already actively exploring some of those, and are open to and may well expand that. There's obviously many potential targets that could influence the outcome if you were to inhibit them.

當然。我們已經在考慮並積極探索其中的一些方案，並且對此持開放態度，很可能會擴大這些方案的範圍。顯然，如果抑制某些潛在靶點，可能會影響結果。

And we look at these opportunities all the time, we have a significant operation studying those, and we have a lot of inbound requests to combine things. And we try to prioritize them based on their scientific data behind them. And for sure, we'll continue to do that.

我們一直在關注這些機會，我們投入了大量精力研究這些機會，而且我們收到了很多整合各種資源的請求。我們會根據背後的科學數據來判斷它們的優先順序。我們肯定會繼續這樣做。

Thank you.

謝謝。

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

謝謝。問答環節到此結束。現在我想把時間交還給馬克，讓他做總結發言。

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

謝謝接線生。感謝大家今天的參與，也感謝大家一直以來對 Revolution Medicines 的支持。

This does conclude the program. You may now disconnect.

節目到此結束。您現在可以斷開連線了。