Revolution Medicines, Inc. (RVMD) 2026 Q1 法說會逐字稿

Good day and thank you for standing by. Welcome to the Revolution Medicines Q1 2026 earnings call.

各位好，感謝您稍候。歡迎參加 Revolution Medicines 2026 年第一季財報電話會議。

(Operator Instructions) Please be advised that today's conference is being recorded.

(接線員指示) 請注意，今天的會議將被錄音。

I would now like to hand it over to Ryan Asay, Senior VP of Corporate Affairs. Ryan, you have the floor.

現在我想把電話交給企業事務資深副總裁 Ryan Asay。Ryan，請開始。

Thank you, operator. Welcome, everyone, to the first-quarter 2026 earnings call.

謝謝，接線員。歡迎各位參加 2026 年第一季財報電話會議。

Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicine's Chairman and Chief Executive Officer; Dr. Alan Sandler, our Chief Development Officer; and Jack Anders, the Chief Financial Officer.

今天與我一同出席的有：Revolution Medicines 董事長兼執行長 Mark Goldsmith 博士；我們的開發長 Alan Sandler 博士；以及財務長 Jack Anders。

Dr. Steve Kelsey, our President of R&D; Dr. Wei Lin, our Chief Medical Officer; and Anthony Mancini, our Chief Global Commercialization Officer, will join us for the Q&A portion of today's call.

我們的研發總裁 Steve Kelsey 博士、醫務長 Wei Lin 博士，以及全球商業化長 Anthony Mancini，將在今天的問答環節加入。

We 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 forward-looking statements.

我們想提醒各位，我們在本次電話會議中所做的某些陳述屬於前瞻性陳述。由於此類陳述涉及未來事件，且受多項風險與不確定性影響，實際結果可能與前瞻性陳述所述存在重大差異。

For a full discussion of these risks and uncertainties, please review our annual report on Form 10-K and our quarterly report on Form 10-Q that are filed with the US Securities and Exchange Commission.

如需完整了解這些風險與不確定性，請查閱我們向美國證券交易委員會提交的 10-K 年度報告及 10-Q 季度報告。

This afternoon, we've released financial results for the quarter ended March 31, 2026, and recent corporate updates. The press release and updated corporate presentation are available on the Investors section of our website at revmed.com.

今天下午，我們已發布截至 2026 年 3 月 31 日止季度的財務結果及近期公司更新。新聞稿與更新後的公司簡報可於我們網站 revmed.com 的「投資人」專區取得。

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 Medicines 董事長兼執行長 Mark Goldsmith 博士。Mark？

Thanks, Ryan. It's good to be with you this afternoon to discuss the tremendous progress we've made in 2026.

謝謝你，Ryan。很高興今天下午與各位一同討論我們在 2026 年取得的重大進展。

This is a pivotal moment for our organization and for patients worldwide living with pancreatic cancer who are in need of new therapeutic options. It is anchored by the top-line read-out for RASolute 302 last month, in which daraxonrasib monotherapy demonstrated an unprecedented improvement in overall survival compared with chemotherapy in patients with previously treated metastatic pancreatic cancer.

這對我們組織而言是關鍵時刻，對全球亟需新治療選項的胰臟癌患者亦然。這一切以我們上個月公布的 RASolute 302 主要結果為基礎：daraxonrasib 單藥治療在既往接受治療的轉移性胰臟癌患者中，相較化療展現前所未有的整體存活期改善。

The RASolute 302 results represent a transformative advance for patients. They also firmly validate our pioneering RAS(ON) inhibitor strategy and reinforce its potential to improve outcomes in RAS-driven cancers.

RASolute 302 的結果代表對患者具有變革性的進展。同時也堅實驗證我們開創性的 RAS(ON) 抑制劑策略，並強化其在 RAS 驅動癌症中改善療效的潛力。

High investor conviction enabled a historic $2 billion dual-tranche capital raise that will allow us to continue our important work broadly, advancing our current portfolio of four ground-breaking clinical-stage oral RAS(ON) inhibitors and bringing forward the next wave of innovation targeting RAS-addicted cancers, including our new class of catalytic RAS(ON) inhibitors.

投資人高度信心促成史無前例的 20 億美元雙分期募資，使我們得以更廣泛地持續推進重要工作：推動目前由四款突破性的臨床階段口服 RAS(ON) 抑制劑所構成的產品組合，並帶來下一波針對 RAS 依賴型癌症的創新，包括我們新一類的催化型 RAS(ON) 抑制劑。

On today's call, following my remarks, I'll pass the call over to Dr. Alan Sandler, who will provide an overview on the recent clinical progress we've made across our portfolio, including the most recent data presented at the American Association for Cancer Research Annual Meeting. Jack Anders will then summarize our first-quarter financial results, before we open the call to Q&A.

在我致詞之後，我將把電話交給 Alan Sandler 博士，他將概述我們在整體產品組合上的近期臨床進展，包括在美國癌症研究協會（AACR）年會上發表的最新數據。之後 Jack Anders 將總結第一季財務結果，接著我們將開放問答。

Let me first spend a few moments talking about RASolute 302, a global Phase 3 trial evaluating daraxonrasib monotherapy in patients with previously treated pancreatic cancer.

我先花幾分鐘談談 RASolute 302，這是一項全球第三期試驗，評估 daraxonrasib 單藥治療於既往接受治療之胰臟癌患者的療效。

The top-line read-out for daraxonrasib marked a major milestone in this disease, significantly raising the bar in the development of new treatments for patients living with pancreatic cancer, the most RAS-addictive of all human cancers.

daraxonrasib 的主要結果讀出是此疾病領域的一項重大里程碑，顯著提高了為胰臟癌患者開發新療法的標準；胰臟癌是所有人類癌症中最依賴 RAS 的癌種。

RASolute 302 daraxonrasib demonstrated unprecedented impact, meeting its primary and key secondary endpoints; and showing statistically significant and clinically meaningful improvement in progression-free survival and overall survival compared to standard-of-care chemotherapy.

RASolute 302 中的 daraxonrasib 展現前所未有的影響力，達成主要與關鍵次要終點；並相較標準治療化療，在無惡化存活期與整體存活期上呈現具統計顯著性且具臨床意義的改善。

In the overall intent-to-treat study population, which includes patients carrying tumors with or without an identified RAS mutation, daraxonrasib drove a 60% reduction in the risk of death compared with chemotherapy and with a median overall survival exceeding one year.

在整體意向治療（ITT）族群中（包含腫瘤帶有或未帶有已辨識 RAS 突變的患者），daraxonrasib 相較化療使死亡風險降低 60%，且整體存活期中位數超過一年。

Daraxonrasib was generally well tolerated. No new safety signals were observed.

daraxonrasib 整體耐受性良好。未觀察到新的安全性訊號。

These are dramatic practice-changing results. Our focus now is on moving with urgency to bring this potential new option to patients. We intend to submit a New Drug Application to the US Food and Drug Administration under the FDA Commissioner's National Priority Voucher program. We'll also execute our plan to file with other global regulatory authorities.

這些結果將大幅改變臨床實務。我們目前的重點是以最高急迫性推進，將這項潛在新選擇帶給患者。我們計畫透過 FDA 署長的「國家優先審查憑證」計畫，向美國食品藥物管理局提交新藥申請（NDA）。我們也將依計畫向其他全球監管機構提出申請。

Last week, we reported that the FDA issued a safe to proceed letter, allowing us to initiate an expanded access treatment protocol for daraxonrasib in patients with previously treated metastatic pancreatic cancer. This will allow us to move as quickly as possible to ensure safe and equitable access to daraxonrasib for eligible patients in the US.

上週我們報告，FDA 已發出可安全推進（safe to proceed）函，允許我們啟動 daraxonrasib 的擴大使用治療方案，適用於既往接受治療之轉移性胰臟癌患者。這將使我們能以最快速度推進，確保符合資格的美國患者能安全且公平地取得 daraxonrasib。

We were also pleased to announce recently that RASolute 302 will be featured in the plenary session of this year's American Society of Clinical Oncology, or ASCO, Annual Meeting in Chicago. We and the investigators look forward to sharing detailed results with the scientific community at that time.

我們也很高興近日宣布，RASolute 302 將在今年於芝加哥舉行的美國臨床腫瘤學會（ASCO）年會全體大會（plenary session）中發表。我們與研究者期待屆時向科學界分享更詳細的結果。

I'll now pass the call over to Alan to walk through some recent clinical program updates. Alan?

接下來我把電話交給 Alan，請他說明近期臨床計畫的更新。Alan？

Thanks, Mark.

謝謝你，Mark。

The extraordinary results from RASolute 302 validate our tricomplex inhibitor platform and give us increased confidence in daraxonrasib's potential in earlier treatment lines in pancreatic cancer. This confidence was reinforced at AACR, where we shared updated clinical data from the Phase 1/2 studies for daraxonrasib monotherapy and in combination with chemotherapy in first-line metastatic pancreatic cancer.

RASolute 302 的卓越結果驗證了我們的三元複合體（tricomplex）抑制劑平台，並讓我們對 daraxonrasib 在胰臟癌更早期治療線別中的潛力更具信心。在 AACR 上，我們分享了 daraxonrasib 單藥以及與化療合併用於第一線轉移性胰臟癌之第一/二期研究的更新臨床數據，進一步強化了這份信心。

Both the monotherapy and combination cohorts demonstrated encouraging preliminary durability data.

單藥與合併治療兩個隊列皆呈現令人鼓舞的初步持久性（durability）數據。

In the monotherapy study, while median progression-free survival and median overall survival were not mature, as of the data cut-off, the Kaplan-Meier estimates at six months were 71% and 83%, respectively. In the combination of daraxonrasib with gemcitabine and nab-paclitaxel, the Kaplan-Meier estimates at six months for progression-free survival. Overall survival were 84% and 90%, respectively.

在單藥研究中，雖然截至資料截止日，無惡化存活期中位數與整體存活期中位數尚未成熟，但 Kaplan-Meier 於 6 個月的估計值分別為 71% 與 83%。在 daraxonrasib 與吉西他濱（gemcitabine）及白蛋白結合型紫杉醇（nab-paclitaxel）的合併治療中，Kaplan-Meier 於 6 個月的無惡化存活期。整體存活期估計值分別為 84% 與 90%。

Across both studies, daraxonrasib's safety and tolerability profile remained consistent with earlier findings in this patient population, with no new safety signals observed.

在兩項研究中，daraxonrasib 的安全性與耐受性特徵皆與先前在此患者族群中的發現一致，未觀察到新的安全性訊號。

These compelling results strongly support our decision to rapidly advance RASolute 303, our Phase 3 study evaluating both daraxonrasib monotherapy and daraxonrasib in combination with chemotherapy in first-line metastatic disease. The trial is enrolling globally.

這些具說服力的結果強力支持我們迅速推進 RASolute 303 的決策；該第三期研究將評估 daraxonrasib 單藥以及 daraxonrasib 與化療合併用於第一線轉移性疾病。該試驗正在全球招募中。

In addition to our first and second-line daraxonrasib registrational studies in pancreatic cancer, patient enrollment is ongoing in RASolute 304, our registrational trial of daraxonrasib monotherapy in the adjuvant setting in patients with resectable disease, following conventional surgery and perioperative chemotherapy.

除我們在胰臟癌第一線與第二線的 daraxonrasib 註冊性研究外，RASolute 304 也正持續收案；該試驗為 daraxonrasib 單藥於可切除疾病患者之輔助治療（adjuvant）情境的註冊性試驗，患者在接受傳統手術及圍手術期化療後納入。

We are also making progress in two registrational studies for zoldonrasib, a covalent RAS(ON) G12D-selective inhibitor in first-line pancreatic cancer. We have initiated RASolute 305, a randomized, double-blind, placebo-controlled registrational trial evaluating zoldonrasib in combination with investigators' choice of chemotherapy, either gemcitabine and nab-paclitaxel or modified FOLFIRINOX compared with placebo plus chemotherapy.

我們也在兩項針對 zoldonrasib 的註冊性研究中取得進展；zoldonrasib 為一種共價型 RAS(ON) G12D 選擇性抑制劑，用於一線胰臟癌。我們已啟動 RASolute 305，這是一項隨機、雙盲、安慰劑對照的註冊性試驗，評估 zoldonrasib 與研究者選擇之化學治療合併使用（可選擇吉西他濱與白蛋白結合型紫杉醇，或改良版 FOLFIRINOX），並與安慰劑加化學治療進行比較。

We remain on track to initiate RASolute 309, our first registrational study to evaluate the RAS(ON) inhibitor doublet combination of zoldonrasib with daraxonrasib in the second half of the year.

我們仍按計畫於今年下半年啟動 RASolute 309，這將是我們首項註冊性研究，用以評估 RAS(ON) 抑制劑雙聯合併療法：zoldonrasib 與 daraxonrasib 的組合。

Moving to non-small cell lung cancer, another focus of development for RAS(ON) inhibitors, with approximately 30% of non-small cell lung cancers harboring a RAS mutation, including 18% with non-G12C mutations, unmet needs in non-small cell lung cancer remain a priority that we aim to address through several ongoing and planned registrational studies.

接著談到非小細胞肺癌，這也是 RAS(ON) 抑制劑的另一個研發重點；約有 30% 的非小細胞肺癌帶有 RAS 突變，其中 18% 為非 G12C 突變。非小細胞肺癌仍存在未被滿足的醫療需求，這仍是我們的優先事項；我們希望透過多項正在進行及規劃中的註冊性研究來加以解決。

Beginning with daraxonrasib, we continue to enroll patients globally in RASolve 301, our global randomized trial evaluating daraxonrasib monotherapy in previously treated patients.

以 daraxonrasib 為例，我們持續在全球招募患者參與 RASolve 301，這是我們的全球隨機試驗，評估 daraxonrasib 單藥治療於既往接受治療之患者。

Based on the strength of the Phase 1 results for daraxonrasib monotherapy in non-small cell lung cancer, as well as additional confidence from the recent positive RASolute 302 results, we are expanding the RASolve 301 study to increase the statistical power of the overall survival component of the dual primary endpoint.

基於 daraxonrasib 單藥在非小細胞肺癌第一期試驗結果的強勁表現，以及近期 RASolute 302 正面結果所帶來的額外信心，我們正在擴大 RASolve 301 研究，以提升雙主要終點中整體存活（overall survival）組成部分的統計檢定力。

Enrollment is going well. We anticipate substantially completing enrollment in the expanded study this year. We also expect to disclose our plans regarding daraxonrasib's combination therapy in first-line non-small-cell lung cancer this year.

招募進展良好。我們預期今年將在擴大後的研究中大致完成招募。我們也預期今年將揭露關於 daraxonrasib 於一線非小細胞肺癌合併療法的規劃。

Turning to G12D non-small cell lung cancer, at AACR, we presented updated clinical data for zoldonrasib monotherapy in a subset of patients who had previously been treated with immune checkpoint inhibitors and platinum chemotherapy.

轉到 G12D 非小細胞肺癌，在 AACR 上，我們發表了 zoldonrasib 單藥的更新臨床數據，該數據來自一個患者子群：先前曾接受免疫檢查點抑制劑與含鉑化療治療。

Zoldonrasib was generally well-tolerated and demonstrated a safety profile consistent with previously reported findings. Zoldonrasib demonstrated encouraging clinical activity, with a confirmed objective response rate of 52%, disease control rate of 93%, and a median progression-free survival of 11.1 months.

Zoldonrasib 整體耐受性良好，且其安全性概況與先前報告的發現一致。Zoldonrasib 展現令人鼓舞的臨床活性：確認的客觀反應率為 52%，疾病控制率為 93%，中位無惡化存活期為 11.1 個月。

Overall survival data were immature at the time of analysis. The estimated survival rate at 12 months was 73%, while the median had not yet been reached, which is encouraging data at this early look.

在分析時，整體存活數據尚未成熟。12 個月的估計存活率為 73%，而中位數尚未達到；在這次早期觀察中，這是令人鼓舞的數據。

We continue to believe deeply in the potential of zoldonrasib, given its compelling safety and tolerability profile; and encouraging clinical activity, which strongly support our plan to advance zoldonrasib across monotherapy and combination settings in lung cancer and other RAS G12D-driven cancers.

鑑於 zoldonrasib 具備具說服力的安全性與耐受性概況，以及令人鼓舞的臨床活性，我們仍深信其潛力；這些結果強力支持我們的計畫：在肺癌及其他由 RAS G12D 驅動的癌症中，推進 zoldonrasib 於單藥與合併治療等不同情境的開發。

Building on the strength of our monotherapy data, we are preparing to initiate, in the first half of this year, RASolve 308, a global, double-blind, placebo-controlled registrational trial evaluating zoldonrasib in combination with the KEYNOTE-189 regimen, which is the standard of care in first-line treatment for metastatic non-small cell lung cancer compared to the KEYNOTE-189 regimen with placebo.

在單藥數據的堅實基礎上，我們正準備於今年上半年啟動 RASolve 308，這是一項全球、雙盲、安慰劑對照的註冊性試驗，評估 zoldonrasib 與 KEYNOTE-189 方案合併使用；KEYNOTE-189 方案為轉移性非小細胞肺癌一線治療的標準照護，並與 KEYNOTE-189 方案合併安慰劑進行比較。

For patients with G12C non-small cell lung cancer, elironrasib, a RAS(ON) mutant-selective inhibitor, has demonstrated a differentiated and compelling clinical profile in both G12C inhibitor-naïve and G12C inhibitor-experienced lung cancer patients.

對於 G12C 非小細胞肺癌患者，elironrasib（RAS(ON) 突變選擇性抑制劑）在未曾使用 G12C 抑制劑以及曾使用過 G12C 抑制劑的肺癌患者中，均展現出具差異化且引人注目的臨床概況。

We remain on track to share an update on our elironrasib registrational strategy this year.

我們仍按計畫於今年分享 elironrasib 的註冊性策略更新。

Our third RAS-addictive cancer focus is colorectal cancer, which remains an area of high unmet need and interest for the company. We have a range of combination studies underway designed to better understand this genetically complex and heterogeneous disease, including studies to evaluate RAS(ON) inhibitor doublet combination and RAS(ON) inhibitors in combination with current standards of care and with other targeted drugs.

我們第三個以 RAS 依賴性（RAS-addictive）癌症為重點的領域是大腸直腸癌；這仍是高度未被滿足的需求領域，也是公司高度關注的方向。我們正在進行一系列合併治療研究，旨在更深入理解這個在基因層面複雜且異質性高的疾病；其中包括評估 RAS(ON) 抑制劑雙聯合併療法，以及 RAS(ON) 抑制劑與現行標準照護及其他標靶藥物的合併使用。

We remain on track to share combination data this year, as we work to prioritize registrational opportunities.

在我們致力於優先排序註冊性機會的同時，我們仍按計畫於今年分享合併治療數據。

I'll conclude with brief highlights on two of our early-stage programs:

最後，我將以兩項早期階段計畫的重點簡要作結：

We continue enrolling patients in the first-in-human trial of RMC-5127, our fourth RAS(ON) inhibitor. RMC-5127 is selective for RAS G12V, the second most common RAS variant in solid tumors. We expect to identify a recommended monotherapy Phase 2 dose for this compound in the second half of 2026.

我們持續在 RMC-5127 的首次人體試驗中招募患者；RMC-5127 是我們第四款 RAS(ON) 抑制劑。RMC-5127 對 RAS G12V 具選擇性；G12V 是實體腫瘤中第二常見的 RAS 變異。我們預期在 2026 年下半年為此化合物確定建議的單藥第二期劑量。

Finally, AACR brought with it the opportunity to showcase our new class of innovative mutant-targeted catalytic RAS-ON inhibitors. These inhibitors are designed to promote the conversion of mutant RAF in its active GTP-bound RAS(ON) state back to the inactive GTP-bound RAS(OFF) state, thereby mimicking the normal physiologic regulation of wild-type breasts.

最後，AACR 也提供了機會，讓我們展示一個全新類別的創新突變靶向催化型 RAS-ON 抑制劑。這些抑制劑的設計目的，是促進處於活性、GTP 結合之 RAS(ON) 狀態的突變 RAF 轉回不活性、GTP 結合之 RAS(OFF) 狀態，從而模擬野生型蛋白的正常生理調控。

These pre-clinical data demonstrated that at, well-tolerated doses, RM-055 achieved robust and durable anti-tumor activity across KRAS G12 mutant xenograft models of pancreatic cancer, non-small cell lung cancer, and colorectal cancer.

這些臨床前數據顯示，在耐受性良好的劑量下，RM-055 在胰臟癌、非小細胞肺癌與大腸直腸癌的 KRAS G12 突變異種移植模型中，均達到強勁且持久的抗腫瘤活性。

Notably, tumors that had escaped prior RAS inhibitor treatment were sensitive to RM-055, which drove deep and durable regressions. Its compelling differentiated profile warrants clinical investigation of its potential to counter emergent drug resistance and to extend clinical benefit.

值得注意的是，先前已逃逸 RAS 抑制劑治療的腫瘤對 RM-055 仍具敏感性，並出現深度且持久的腫瘤退縮。其具說服力且差異化的特徵，值得進一步以臨床研究探討其對抗新出現的藥物抗性、並延長臨床獲益的潛力。

We remain on track to initiate a first-in-human clinical trial in the fourth quarter.

我們仍按計畫於第四季啟動首次人體臨床試驗。

With that, I'd like to pass the call back over to Mark. Mark?

接下來，我想把電話會議交回給 Mark。Mark？

Thanks, Alan.

謝謝，Alan。

In addition to the substantial R&D progress we've made across our pipeline, we continue to be very gratified by the build-out of our commercialization infrastructure and operational capabilities to support the company's global commercialization ambitions.

除了我們在整體研發管線上取得的重大進展之外，我們也持續對商業化基礎建設與營運能力的建置感到非常欣慰，這些將支援公司全球商業化的企圖與目標。

We've established the operational wherewithal required to move with speed and agility, focused initially in the US and extending into priority international regions. We are resourcing our efforts to ensure that we have the best strategies, tactics, operational capabilities, and people to bring daraxonrasib with urgency to patients, pending regulatory approvals.

我們已建立所需的營運能力，以快速且靈活地推進工作；初期聚焦於美國，並延伸至優先的國際地區。我們正投入資源以確保具備最佳的策略、戰術、營運能力與人才，在取得監管核准的前提下，以緊迫感將 daraxonrasib 帶給患者。

We expect to be launch-ready under best-case approval-timing scenarios.

在最理想的核准時程情境下，我們預期可達到上市準備就緒。

We have experienced and talented executives leading our commercialization team across medical affairs, market access, marketing, and sales. These groups are deeply engaged in market preparedness and assessment; planning; physician and advocacy engagement, sharpening operational capabilities and conducting other launch readiness activities.

我們的商業化團隊由具經驗且才華洋溢的高階主管領導，涵蓋醫藥事務、市場准入、行銷與銷售。這些團隊深度投入市場準備與評估、規劃、醫師與倡議團體互動，並強化營運能力及執行其他上市準備活動。

We recently appointed several experienced leaders across the Asia-Pacific and European regions, including Neil MacGregor as our General Manager for APAC; Tetsuo Endo as General Manager for Japan; and Martin Voelkl as General Manager for Germany.

我們近期在亞太與歐洲地區任命了多位資深領導者，包括：Neil MacGregor 擔任亞太區（APAC）總經理；遠藤哲夫（Tetsuo Endo）擔任日本總經理；以及 Martin Voelkl 擔任德國總經理。

I'd now like to turn the call over to Jack Anders, our Chief Financial Officer, to summarize our first-quarter financial results. Jack?

接下來我想把電話會議交給我們的財務長 Jack Anders，請他總結第一季財務結果。Jack？

Thanks, Mark.

謝謝你，Mark。

We ended the first quarter of 2026 with $1.9 billion in cash and investments; and further strengthened our financial position after the quarter with $2.1 billion in net proceeds from more concurrent upsized offerings of common stock and convertible debt in April.

我們在2026年第一季結束時，持有現金及投資共19億美元；並且在季後於4月透過同時進行、且規模上調的普通股與可轉換債發行，取得21億美元的淨募資款，進一步強化了我們的財務狀況。

Before we dive into the income statement for the quarter, I'd like to highlight that our stock-based compensation expense for the quarter was higher than usual and explain the reason behind it.

在我們深入說明本季損益表之前，我想先強調本季的股票基礎給付（股權激勵）薪酬費用高於以往，並說明其背後原因。

Stock-based compensation expense was $87.3 million for the quarter ended March 31, 2026, compared to $25.1 million for the quarter ended March 31, 2025.

截至2026年3月31日止季度的股票基礎給付薪酬費用為8,730萬美元，相較之下，截至2025年3月31日止季度為2,510萬美元。

In the first quarter of 2026, the company updated its equity compensation program to introduce competitive retirement benefits for employees who meet specific minimum age and service requirements. The modification of this program resulted in an incremental $44.6 million in stock-based compensation for the first quarter of 2026.

在2026年第一季，公司更新了其股權薪酬計畫，為符合特定最低年齡與服務年限要求的員工引入具競爭力的退休福利。此計畫的修改使2026年第一季新增4,460萬美元的股票基礎給付薪酬。

This incremental expense was primarily due to the accelerated timing of recognition of stock-based compensation expense originally scheduled in future periods for outstanding eligible awards.

這筆新增費用主要是因為，原本預計在未來期間認列、且針對符合資格之未到期獎勵的股票基礎給付薪酬費用，其認列時點被加速。

As a result of this timing pull-in, we expect higher non-recurring lumpiness in stock-based compensation expense for the first half of 2026, with stock-based compensation expense decreasing and returning to a more normalized trajectory in the second half of the year.

由於認列時點前移，我們預期2026年上半年股票基礎給付薪酬費用將出現較高、非經常性的波動；而在下半年該費用將下降並回到較為正常化的走勢。

As a result of this change, the company is increasing its estimate of full-year 2026 stock-based compensation expense by approximately $80 million and now expects full-year 2026 stock-based compensation expense to be between $260 million and $280 million.

受此變更影響，公司將2026年全年股票基礎給付薪酬費用的估計上調約8,000萬美元，並預期2026年全年股票基礎給付薪酬費用將介於2.6億至2.8億美元之間。

Additionally, the company is also updating its projected GAAP operating expense guidance to reflect this expected increase in stock-based compensation expense and now expects full-year GAAP operating expenses to be between $1.7 billion and $1.8 billion.

此外，公司也更新其GAAP營業費用指引，以反映股票基礎給付薪酬費用預期增加的影響，並預期2026年全年GAAP營業費用將介於17億至18億美元之間。

Moving to expenses for the quarter, R&D expenses for the first quarter of 2026 were $344.0 million compared to $205.7 million for the first quarter of 2025. This increase was primarily due to the higher clinical trial and manufacturing expenses for daraxonrasib and zoldonrasib due to acceleration of the pace and expansion of these programs.

接著看本季費用，2026年第一季研發（R&D）費用為3.44億美元，相較於2025年第一季的2.057億美元。此增加主要是因daraxonrasib與zoldonrasib計畫加速推進並擴大規模，導致臨床試驗與製造費用提高。

R&D expenses were also higher as a result of increased headcount costs and higher stock-based compensation expense, as described earlier.

如前所述，研發費用也因人員編制成本增加以及較高的股票基礎給付薪酬費用而上升。

G&A expenses for the first quarter of 2026 were $101.3 million compared to $35.0 million for the first quarter of 2025. The increase in G&A expenses was primarily due to higher stock-based compensation expense, as described earlier; increased headcount costs; increased commercial preparation activities; and higher administrative costs.

2026年第一季一般及行政（G&A）費用為1.013億美元，相較於2025年第一季的3,500萬美元。G&A費用增加主要是由於如前所述較高的股票基礎給付薪酬費用、人員編制成本增加、商業化準備活動增加，以及較高的行政成本。

Net loss for the first quarter of 2026 was $453.8 million compared to $213.4 million for the first quarter of 2025. The increase in net loss was due to higher operating expenses.

2026年第一季淨損為4.538億美元，相較於2025年第一季的2.134億美元。淨損增加係因營業費用較高所致。

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

以上為財務更新。我現在把電話交回給Mark。

Thank you, Jack.

謝謝你，Jack。

The remarkable start to 2026 is the result of years of unwavering dedication, relentless perseverance, and hard work by our team and collaborators standing on the shoulders of others.

2026年令人矚目的開局，是我們團隊與合作夥伴多年來堅定投入、不懈努力與辛勤工作，在前人基礎上持續累積的成果。

With the unprecedented performance of daraxonrasib monotherapy in the RASolute 302 study, we believe we are in the position to change the standard of care for patients living with pancreatic cancer, subject to regulatory review and approval.

憑藉daraxonrasib單藥在RASolute 302研究中前所未見的表現，我們相信在監管審查與核准的前提下，我們有機會改變胰臟癌患者的標準治療。

The global response to the RASolute 302 data has been overwhelming. The news brings with it hope and possibility for patients, physicians, and the advocacy community that have all been waiting too long for new, more effective treatment options.

全球對RASolute 302數據的反應非常熱烈。這則消息為長久以來一直等待更有效新療法的患者、醫師與倡議團體帶來希望與可能性。

We are now an important step closer to fulfilling our mission of discovering, developing, and delivering innovative, targeted medicines to patients living with cancer.

我們現在距離實現使命——發現、開發並將創新且具標靶性的藥物帶給癌症患者——又更近了一大步。

We have an extraordinary opportunity. We take very seriously the responsibility that goes with it.

我們擁有一個非凡的機會。我們非常嚴肅看待隨之而來的責任。

Before I close, I'd like to recognize our continuing partnerships with patients and caregivers; healthcare providers; and investors, as well as the remarkable dedication and efforts of RevMed employees. It requires the ongoing support of all of our partners and constituencies to do revolutionary work, on behalf of patients.

在結束前，我想感謝我們與患者及照護者、醫療照護提供者以及投資人之間持續的合作關係，也要肯定RevMed員工非凡的投入與努力。要代表患者推動革命性的工作，需要我們所有合作夥伴與利害關係人的持續支持。

With that, I'll turn the call over to the operator for the question-and-answer portion of the call.

接下來，我把電話交給接線員，進入問答環節。

Thank you. At this time, we will conduct a question-and-answer session.

謝謝。現在我們將進行問答時段。

(Operator Instructions)

(接線員指示)

Cory Kasimov, Evercore ISI.

Evercore ISI 的 Cory Kasimov。

Congrats on all the recent very exciting progress.

恭喜近期取得這些非常令人振奮的進展。

I wanted to ask: You recently noted you could share data at a medical meeting that supports the rationale for RASolute 309, the Phase 3 front-line PDAC trial, looking at zoldonrasib plus daraxonrasib versus chemo.

我想請教：你們最近提到，可能會在一場醫學會議上分享支持RASolute 309（第一線PDAC的第三期試驗）之科學依據的數據，該試驗比較zoldonrasib合併daraxonrasib與化療。

Would this include durability data or just response rate, as we've seen with some of your initial disclosures? Maybe more importantly, how much additive efficacy would you be looking for here to say it's clinically meaningful to justify the combination over the exciting monotherapy results we've seen with both of these agents?

這會包含療效持久性（durability）數據，還是僅有反應率，就像我們在你們先前一些初步揭露中看到的那樣？也許更重要的是，相較於我們已看到這兩個藥物單藥治療的亮眼結果，你們會希望在此看到多大的額外療效提升，才會認為具有臨床意義、足以支持以聯合療法取代單藥？

Thanks, Cory. I appreciate your comments and question.

謝謝你，Cory。感謝你的評論與提問。

It's probably too early for us to lay out what that presentation would look like. We typically don't forecast it.

我們現在可能還太早，無法說明那場發表會呈現的樣貌。我們通常不會事先預告。

We'll show what we have. We think it will justify our plans. We'll provide that in due course.

我們會展示我們所掌握的資料。我們認為這將能支持我們的計畫。我們會在適當時機提供。

The second question, also, probably and unfortunately, we can't be too helpful about what's the threshold for added value that justifies doing that. Of course, we look at the totality of the evidence. We look at the historical benchmarks.

至於第二個問題，恐怕也很遺憾，我們無法就「多少增量價值」才足以支持這麼做提供太多具體說法。當然，我們會看整體證據。我們也會參考歷史基準。

Ultimately, as you implied in your question, durability is the most important parameter.

最終，如你在問題中所暗示的，療效持久性是最重要的參數。

Got it. Thank you.

了解。謝謝。

Charles Zhu, LifeSci Capital.

LifeSci Capital 的 Charles Zhu。

Thank you for taking my questions. Congrats on (technical difficulty) -- everything.

謝謝讓我提問。恭喜（技術問題）——一切。

I've got a (technical difficulty) -- at the opposite end of the spectrum.

我有一個（技術問題）——在光譜的另一端。

One, (technical difficulty) -- to accommodate on your expanded access program for daraxonrasib (technical difficulty) -- what are the potential implications, as you start thinking about potentially converting?

第一，（技術問題）——關於你們為daraxonrasib擴大使用計畫（expanded access program）所做的安排（技術問題）——當你們開始思考可能的轉換時，潛在影響會是什麼？

Hey, Charles. Charles, we're not able to pick up what you're saying.

嗨，Charles。Charles，我們聽不清楚你在說什麼。

Stacy, I don't know if there's anything you can do on your side to improve the audio quality.

Stacy，我不確定你那邊是否能做些什麼來改善音訊品質。

Charles, are you in a good position to speak with us?

Charles，你現在的位置方便跟我們通話嗎？

Yeah. Will get Charles back queued up.

可以。我們會把Charles重新排入隊列。

(multiple speakers) --

(多位發言者) --

Michael Schmidt, Guggenheim Securities.

Michael Schmidt，Guggenheim Securities。

Yeah. Hey, guys. Thanks for taking my questions.

是的。嗨，各位。謝謝讓我提問。

Again, congrats on the RASolute 302 data. I'm looking forward to the full data presentation at ASCO.

再次恭喜 RASolute 302 的數據。我很期待在 ASCO 上完整數據的發表。

Yeah. A question on the EAP program. I know this was just announced a few days ago. But, Mark, I don't know if you could comment what you're seeing, so far, in terms of demand for the EAP program? What do you think -- how many patients could particularly benefit from this, prior to officially receiving FDA approval?

是的。關於 EAP 計畫有個問題。我知道這是在幾天前才剛宣布。不過，Mark，我不知道你是否能評論一下，到目前為止你們看到的 EAP 計畫需求情況？你認為——在正式獲得 FDA 核准之前，大概有多少病患可能特別能從中受益？

And then, maybe just -- if you could share your view of the size of the second-line pancreatic cancer opportunity: Based on your market research, how many patients in the US do you think would be treatment-eligible for the daraxonrasib, based on the 302 study?

另外，也許——如果你能分享你對二線胰臟癌機會規模的看法：根據你們的市場調研，你認為在美國有多少病患會符合 daraxonrasib 的治療資格（以 302 研究為基礎）？

Thanks, Michael. Nice to hear from you.

謝謝你，Michael。很高興聽到你的聲音。

On the first question, of course, we're working hard to get in a position to be providing drugs to those who need it. The demand has been very clear from the moment that it was announced. We don't expect that to slow down anytime soon.

關於第一個問題，當然，我們正努力讓自己處於能夠向有需要的人提供藥物的位置。從宣布的那一刻起，需求就非常明確。我們不預期這股需求在短期內會放緩。

We're putting all the resources that we can on it. We'll meet that need.

我們正投入所有能投入的資源。我們會滿足這個需求。

I can't really give you a projection, as to the number. I don't know how we can make that projection. We'll just have to have to play it out.

我其實無法給你一個人數的預估。我不知道我們要如何做出那樣的預估。我們只能讓它自然發展。

I think there is clearly a widespread knowledge of, awareness of, daraxonrasib. Those calls started coming in within minutes after the announcement.

我認為顯然大家對 daraxonrasib 的認知與關注度很高。在公告後幾分鐘內，那些電話就開始湧入。

The size of the second-line opportunity -- Wei way you might want to talk about this. We can't characterize it for you a great depth but we typically think about roughly 60,000 new cases in each year.

至於二線機會的規模——Wei，你可能想談談這點。我們無法非常深入地為你量化，但我們通常會以每年大約 60,000 個新病例來思考。

And then, maybe, Wei can comment on both what's historical attrition and then, also whether or not daraxonrasib might affect that.

然後，也許 Wei 可以同時評論一下歷史上的流失率，以及 daraxonrasib 是否可能影響那個情況。

Yeah. Happy to do that.

是的。很樂意。

These are obviously just estimates, based on clinical practice; a smart comment (inaudible) -- about 60,000 Americans are newly diagnosed each year with pancreatic cancer.

這些顯然都只是基於臨床實務的估算；一個精闢的評論（聽不清）——每年大約有 60,000 名美國人新診斷為胰臟癌。

About 50% to 60% of those patients are diagnosed with metastatic disease. And so those patients are (inaudible) -- what we see first-line therapy with (inaudible) disease.

其中約 50% 到 60% 的病患在診斷時就是轉移性疾病。因此這些病患（聽不清）——我們看到的一線治療是針對（聽不清）疾病。

Typically, because of both the aggressive nature disease, as well as the toxicity of chemotherapy, about half of the patients who received first-line metastatic treatment received subsequent second-line treatment.

一般而言，由於疾病本身的侵襲性，以及化療的毒性，大約只有一半接受轉移性一線治療的病患，會再接受後續的二線治療。

That gives you a sense of the overall attrition, as well as the size.

這能讓你對整體流失率以及規模有個概念。

Just to add to that: That could certainly change in the context of first-line treatment but we don't have anything to address on that point today.

再補充一下：在一線治療的情境下，這當然可能會改變，但我們今天沒有任何內容可以就此點做出回應。

Faisel Khurshid, Jefferies.

Faisel Khurshid，Jefferies。

Hey, guys. Thank you so much for taking the question.

嗨，各位。非常感謝讓我提問。

I just wanted to ask on the RASolve 301 upsizing. Could you clarify what exactly led to the upsizing? What were you powered for before? What are you powered for now? Does this change the timeline from enrollment completion to read-out?

我想問一下 RASolve 301 擴大樣本數的事。你們能否釐清究竟是什麼原因導致擴大？之前的統計檢定力是針對什麼設計的？現在又是針對什麼？這會改變從完成入組到讀出結果的時間線嗎？

Thank you.

謝謝。

Thanks a lot for your question. I'm going answer the second question. And then, Alan Sandler is going to talk about the first.

非常感謝你的問題。我先回答第二個問題。然後 Alan Sandler 會談第一個。

We don't think it will change the timing of the read-out, given the high pace of enrollment and where we stand today. We don't expect to impact our projection -- that we'll complete or substantially complete enrollment this year.

考量到入組速度很快以及我們目前的進度，我們認為這不會改變讀出時間點。我們不預期會影響我們的預估——也就是我們將在今年完成或大致完成入組。

But the more subtle question about the sizing of the trial, Alan can comment on.

至於更細緻的問題，也就是試驗規模的調整，Alan 可以補充。

Sure. Thanks.

好的。謝謝。

An important point is we've realized the importance of overall survival. Given the results that we've seen in 302 and, also, the Phase 1 monotherapy data, we have a very high conviction on our ability to obtain overall survival benefit.

一個重要重點是，我們已經意識到整體存活期（overall survival）的重要性。基於我們在 302 看到的結果，以及第一期單藥治療數據，我們對於取得整體存活期獲益的能力有非常高的信心。

As a result of that, we're going further prioritize overall survival in 301 by expanding the enrollment, as you've noted, going from 420 to 590 patients. That'll increase the statistical power of that component of what is a dual primary endpoint.

因此，我們在 301 中進一步優先考量整體存活期，透過擴大入組——如你所指出，從 420 人增加到 590 人。這將提高該部分（作為雙主要終點之一）的統計檢定力。

Again, as Mark has mentioned, there's a great pace in terms of the patient enrollment. We think that we will substantially complete the enrollment, even with the expanded study this year.

同樣地，如 Mark 所提到，病患入組的速度非常快。即使研究擴大，我們仍認為今年將能大致完成入組。

Got it. Thank you.

了解。謝謝。

Brian Cheng, JP Morgan

Brian Cheng，JP Morgan

Hey, guys. Thanks for taking our questions this afternoon.

嗨，各位。謝謝今天下午回答我們的問題。

Mark, during the call, you said the best-case timing scenario for darax, at launch, across the globe. How should we think about the timing and the cadence, then, for the filing and launches, just specifically across APAC and European regions?

Mark，在電話會議中你提到 darax 在全球上市的最佳情境時程。那我們應該如何看待申報與上市的時間點與節奏，特別是在亞太（APAC）與歐洲地區？

Just on the NDA application towards the FDA, can you give us a little bit more color, a little bit more granularity, in terms of the things that are left to complete?

另外關於向 FDA 提交 NDA 申請，你能否提供更多細節、更具體一些，說明還有哪些事項尚待完成？

Thank you.

謝謝。

Yeah. Thanks, Brian.

是的。謝謝你，Brian。

We can't really give you any specific timing with regard to the filings outside the United States. But, just generally speaking, we are starting with the US filing as the initial priority.

我們無法就美國以外地區的申報提供任何具體時間點。但一般而言，我們會先以美國申報作為首要優先事項。

There will be some sequential framework for filing in other countries. We're already engaged with regulatory authorities outside of the United States in order to make sure that we can deliver what they need and in as timely a manner as possible.

之後會有一個在其他國家依序申報的框架。我們已經與美國以外的監管機關展開互動，以確保我們能提供他們所需的資料，並盡可能及時。

For the NDA, your question was, what's left to deliver? Is that how you put it?

至於 NDA，你的問題是，還有哪些內容需要提交？你是這樣問的嗎？

Yeah. What are the things that are left to complete before you complete the NDA application?

是的。在你們完成 NDA 申請之前，還有哪些事項需要完成？

Well, we've been fully engaged with the FDA for a long time, as you know. Of course, we've (technical difficulty) -- [CMPB] and the breakthrough designations, we've had a higher level of engagement than you might otherwise have.

嗯，我們與 FDA 長期以來一直保持充分互動，你也知道。當然，因為我們（技術問題）——[CMPB] 以及突破性療法認定，我們的互動層級比一般情況更高。

We are providing them information, as it becomes available and mature enough to provide to them. Ultimately, the clinical package is the thing that will be provided.

我們會在資訊可用且成熟到足以提供時，就向他們提交。最終，將提交的是完整的臨床資料包。

I can't give you specific timing on that. There's a full-throttle effort to do it. We feel the urgency around it.

我無法就此提供具體的時間點。我們正全力以赴推進。我們也感受到這件事的急迫性。

Certainly, the question earlier about the EAP provides a pretty strong signal about how urgent that is. We'll continue to move this forward as fully as we possibly can.

當然，先前關於 EAP 的提問，已經相當強烈地傳達了其急迫程度。我們會持續盡可能全面地推進這項工作。

Great. Thanks, Mark.

很好。謝謝你，Mark。

Marc Frahm, TD Cowen.

Marc Frahm，TD Cowen。

Great. Thanks for taking my questions.

很好。謝謝讓我提問。

Maybe following up a little bit on Cory's question earlier, just on the zoldonrasib plus daraxonrasib combo. Can you maybe speak to the 309 design, particularly in light of the 302 finding and the survival data looking better than anything we've ever seen, even in first line?

我想稍微延續先前 Cory 的問題，聚焦在 zoldonrasib 加 daraxonrasib 的聯合療法。你能否談談 309 試驗的設計，特別是考量到 302 的發現，以及存活數據看起來比我們以往見過的任何結果都更好，甚至在一線治療也是如此？

Just why is 309, comparing to chemo, still the right design? Or should it really be switched over to consider daraxonrasib monotherapy as the comparator arm there, at a minimum?

為什麼 309 仍然以化療作為對照，會是正確的設計？或者至少是否應該改成以 daraxonrasib 單藥作為對照組？

One, to get the contribution of parts, but, also just from a clinical execution perspective of where the ball is headed -- seems to be headed in pancreatic cancer.

一方面是為了釐清各組成部分的貢獻，但另一方面，從臨床執行與趨勢來看——在胰臟癌領域似乎正朝那個方向發展。

Yeah. Thanks, Mark. That's a good question. It's a subtle one.

是的。謝謝你，Mark。這是個好問題。而且相當微妙。

Of course, today, standard care is chemotherapy. Until there's a data set that moves the FDA to approve a different treatment -- and a different treatment at the level that people consider the new standard of care -- then chemotherapy is the standard of care.

當然，就目前而言，標準治療是化療。在有一套數據能促使 FDA 核准不同治療——而且該治療達到大家認可的新標準治療水準——之前，化療仍是標準治療。

I think you're inviting me to comment that. Of course, we think daraxonrasib has a real potential in monotherapy but also in combinations in first line.

我想你是在邀請我對此發表看法。當然，我們認為 daraxonrasib 在單藥治療上具有真正的潛力，也同樣在一線的聯合療法中具備潛力。

Among those combinations, chemotherapy is one that we've already provided some early-stage data on. We're quite excited about. That combination is in the 303 trial.

在這些聯合療法之中，化療是我們已經提供過一些早期數據的一種。我們對此相當興奮。這個組合正在 303 試驗中。

We're already going into combinations. It's really just a question of when that bar moves. But we have high confidence that the combination can deliver something that is differentiated from chemotherapy but, also, even from monotherapy.

我們已經在推進各種聯合療法。真正的問題只是那個門檻何時會改變。但我們非常有信心，這個聯合療法能帶來相較化療具差異化的效果，同時也甚至優於單藥治療。

I think the other thing to keep in mind is we do a lot of things where there's overlap in the patient populations that we might be able to serve in different ways. We don't shy away from that, as you know. We've discussed that before.

另外要記住的是，我們做了很多事情，可能在可服務的病人族群上會有重疊，但我們不會因此退縮，你也知道。我們之前也討論過。

Because every patient has his or her own specific needs and giving doctors options -- even if the outcomes on paper may look fairly similar across broad populations, there still may be reasons why one particular patient would benefit or would be perceived to benefit from one particular combination or monotherapy approach versus another.

因為每位病人都有其特定需求，提供醫師更多選項——即使在紙面上、在廣泛族群中的結果看起來相當類似——仍可能有原因使某位特定病人更適合、或被認為更能受益於某一種聯合療法或單藥策略，而非另一種。

Providing the most fulsome set that we can, based on the science and then, ultimately, on the clinical data, increases the chance that we're the ones who are delivering the best possible options for patients. That's the high-level comment.

基於科學，並最終基於臨床數據，盡可能提供最完整的方案組合，能提高我們為病人提供最佳可行選項的機率。以上是高層次的回應。

Jonathan Chang, Leerink Partners.

Jonathan Chang，Leerink Partners。

Hi, guys. Thanks for taking my questions. Congrats on the progress.

嗨，各位。謝謝讓我提問。恭喜進展順利。

Can you talk about your latest thinking on getting to a chemo-free option in front-line pancreatic cancer? What gives you confidence in being able to achieve this? What do you think is the best strategy for giving this?

你能談談你們目前對於在胰臟癌一線治療中實現無化療選項的最新想法嗎？你們有什麼信心能達成這點？你認為最佳的給藥策略是什麼？

Yeah. Thanks, Jonathan. Nice to talk with you.

好的。謝謝你，Jonathan。很高興和你交流。

Well, we just talked about one of those strategies for a chemo-free front-line, which is monotherapy daraxonrasib. I think the data -- single-arm data -- we've shown, so far, are compelling enough that it just very much justified incorporating that into the Phase 3 first-line trial.

嗯，我們剛剛談到其中一種無化療一線策略，也就是 daraxonrasib 單藥治療。我認為我們目前展示的數據——單臂數據——已經足夠有說服力，因此非常合理地把它納入第三期一線試驗。

We'll see how that performs. We have every expectation that it could deliver a chemo-free regimen.

我們會看看它的表現如何。我們完全預期它有機會提供一個無化療療程。

And then, the second option is also one we just talked about, which is combining immune-selective inhibitor with daraxonrasib. That would be a chemo-free strategy. That specific combination of zoldon plus daraxon, of course, is for the 40% of pancreatic cancer cases that are carrying a RAS G12D mutation.

第二個選項也是我們剛剛談到的，也就是把免疫選擇性抑制劑與 daraxonrasib 聯合使用。那會是一種無化療策略。當然，zoldon 加 daraxon 的這個特定組合，是針對約 40% 帶有 RAS G12D 突變的胰臟癌病例。

We have other multi-selective inhibitors directed against additional mutations that are common in or can be found in RAS cancer. We could and would likely fill out that collection of regimens. It just happens that zoldonrasib plus daraxon is on (inaudible) -- vanguard, the work because of the maturity of the compound and the data that we have, so far.

我們還有其他多選擇性抑制劑，針對在 RAS 癌症中常見或可見的其他突變。我們可以、也很可能會把那一整套療程組合補齊。只是剛好 zoldonrasib 加 daraxon 目前在（聽不清）——作為先鋒/領先的工作，因為該化合物的成熟度以及我們目前掌握的數據。

I think those are two very compelling chemo-free regimens. There are others that one can consider. There are immunologic agents that could be combined. There are other targeted agents that could be combined.

我認為這兩種都是非常有吸引力的無化療療程。另外也還有其他可以考慮的方案。也有免疫相關藥物可以聯合。也有其他標靶藥物可以聯合。

We're already exploring, as you know, PRMT5 combination -- PRMT5 inhibitor combination -- et cetera. I'm sure there will be other things to come, over time.

我們也已經在探索——如你所知——PRMT5 聯合療法，也就是 PRMT5 抑制劑的聯合等。我相信隨著時間推進，還會有其他方案出現。

Understood. Thank you.

了解。謝謝。

Charles Zhu, LifeSci Capital.

Charles Zhu，LifeSci Capital。

Hello. Thanks for giving me another stab at this. Can you hear me now?

你好。謝謝讓我再試一次。你們現在聽得到我嗎？

Yes.

聽得到。

All righty. Perfect. I believe a bunch of clinical-type questions were taken so I'll ask one a little bit earlier.

好。太好了。我想很多偏臨床類型的問題都已經被問過了，所以我問一個稍早一點的問題。

RM-055, nice to see your presentation at AACR, as well as some of the work you helped support over at (inaudible) -- lab that was just published yesterday. Can you comment a little bit, perhaps, on RM-055's ability to potentially address daraxonrasib resistance mechanisms that go beyond that of a KRAS amplification?

RM-055，很高興在 AACR 看到你們的發表，也看到你們協助支持的（聽不清）——實驗室那邊的部分工作，昨天剛發表。你能否稍微評論一下，RM-055 是否有能力潛在地處理 daraxonrasib 的抗藥性機制，而不僅僅是 KRAS 擴增？

Can you also talk a little bit about, perhaps, how you might be achieving what appears to be, at least pre-clinically, a wider therapeutic window for RAS mutants over RAS wild types over that which daraxonrasib can achieve?

也請談談你們可能如何達成——至少在臨床前看起來——相較於 daraxonrasib，對 RAS 突變體相對於 RAS 野生型具有更寬的治療窗？

Any color as to how you're accomplishing that mechanistically; and if you can also see that in your pre-clinical models, as you advance that into the clinic. Thank you.

能否補充一些你們在機制上如何做到這點的細節；以及當你們把它推進到臨床時，是否也能在臨床前模型中看到同樣的現象。謝謝。

Thanks, Charles. Those were loud and clear.

謝謝你，Charles。這些問題我們聽得很清楚。

Yeah. Steve Kelsey, I think, will comment on both of those important topics.

是的。我想 Steve Kelsey 會就這兩個重要議題做出回應。

Sure. Yeah.

好的。是的。

I think the RAS amplification can be perceived as a standalone mechanistic basis for escape from daraxonrasib but it also acts as a surrogate for increasing flux through the RAS pathway, generally.

我認為 RAS 擴增可以被視為一個獨立的機制性基礎，用以解釋對 daraxonrasib 的逃逸，但更廣泛而言，它也可作為 RAS 路徑通量增加的替代指標。

In most of the experiments that we've done, RM-055 is a better inhibitor of increased flux through the RAS pathway, generally; particularly when it's going down through a G12 mutation.

在我們做過的大多數實驗中，RM-055 一般而言更能抑制 RAS 路徑通量的增加；特別是當訊號是經由 G12 突變往下傳導時。

I think there is a general principle of escape from daraxonrasib occurring through reactivation of RAS pathway signaling. It's not just amplification of the mutant allele that can do that. I think there's every reason to believe that RM-055 may be effective beyond just pure RAS-mutant amplification.

我認為，從 daraxonrasib 逃逸的一般原則，是透過重新活化 RAS 路徑訊號傳導而發生。不只是突變等位基因的擴增能做到這點。我認為有充分理由相信，RM-055 的有效性可能不僅限於純粹的 RAS 突變擴增。

Your point about therapeutic index, it's all to do with the relative importance of hydrolysis of RAS(ON) back to RAS(OFF) between cancer and normal tissue. Normal tissue, most of the RAS in normal tissue was already in the (OFF) state anyway but it's being catalyzed back. The active RAS is being catalyzed back to RAS(OFF) very effectively by the naturally occurring GAPs.

你提到的治療指數，完全取決於在癌組織與正常組織之間，RAS(ON) 水解回到 RAS(OFF) 的相對重要性。在正常組織中，大多數 RAS 本來就已經處於 (OFF) 狀態，但仍會被催化回去。活化的 RAS 會被天然存在的 GAPs 非常有效地催化回到 RAS(OFF)。

The whole point of RAS-mutation cancer is that that just doesn't happen. The ability of the mutant RAS to withstand that catalytic hydrolysis back to the RAS(OFF) state is very different. It varies from mutation to mutation.

而 RAS 突變癌症的關鍵就在於，這件事不會發生。突變型 RAS 抵抗被催化水解回到 RAS(OFF) 狀態的能力非常不同。而且會因突變型別而異。

But what we've done is very selectively targeted the inability of -- particularly, as I said -- G12-mutant RAS to be hydrolyzed back to RAS(OFF) by forcing it to be hydrolyzed back to RAS(OFF). This drug has almost negligible effect on normal tissue in that respect and a very significant increased a deactivation of mutant RAS in cancer cells.

但我們所做的是非常選擇性地鎖定——尤其如我所說——G12 突變型 RAS 無法被水解回到 RAS(OFF) 的這個弱點，藉由強迫它被水解回到 RAS(OFF)。就這一點而言，這個藥物對正常組織幾乎沒有影響，卻能在癌細胞中非常顯著地增加突變型 RAS 的去活化。

Got it. Thanks for taking the questions. Congrats, again, on everything.

了解。謝謝你回答問題。再次恭喜，一切進展都很棒。

Thank you.

謝謝。

Michael Yee, UBS.

UBS 的 Michael Yee。

Great. Thanks, guys. Congrats on the progress. Two quick ones.

很好。謝謝各位。恭喜進展。兩個簡短問題。

On the colorectal cancer data coming up, can you help guide expectations on how to think about combination with EGFR, given overlapping rash; and how to think about mitigation or how to interpret results, given higher efficacy but also trying to mitigate rash in that strategy?

關於即將公布的結直腸癌數據，考量到皮疹的重疊，你們能否引導我們如何看待與 EGFR 的聯合用藥；以及在該策略中，既追求更高療效、又試圖減輕皮疹時，該如何思考緩解方式或解讀結果？

And then, also, in the first-line PDAC study, which is enrolling, we definitely get huge feedback that it's going to enroll super fast at a number of different sites. Is it safe to assume that there's probably an interim in that study, as well, eventually, once you complete enrollment?

另外，在正在收案的一線 PDAC 研究中，我們確實收到大量回饋，表示在多個不同中心會收案得非常快。是否可以合理假設，等完成收案後，該研究最終也可能會有一次期中分析？

Thanks.

謝謝。

Thanks, Michael. Nice to hear from you.

謝謝你，Michael。很高興聽到你的聲音。

Who wants to address the CRC? Maybe I'll just make the comment that it is true that daraxonrasib, itself, has essentially overlap with the EGFR antagonists from the perspective of suppression RAS signaling that drives the skin side effects.

誰來回答 CRC 的問題？也許我先評論一下：確實，daraxonrasib 本身在抑制 RAS 訊號（而這會驅動皮膚副作用）這一點上，與 EGFR 拮抗劑有本質上的重疊。

That is a harder combination to contemplate. That really doesn't apply, at all, with the mutant-selective inhibitors. That's why the G12C selective inhibitors that launched (inaudible) -- the field -- essentially, sotorasib and adagrasib and, now, others -- can be combined pretty readily.

這會讓聯合用藥更難評估。但這一點完全不適用於突變選擇性抑制劑。這也是為什麼開創（聽不清）——這個領域——的 G12C 選擇性抑制劑，基本上像是 sotorasib、adagrasib，以及現在其他藥物——可以相對容易地進行聯合用藥。

It really fundamentally addresses the whole gap in the EGFR coverage that occurs in the RAS-mutant tumors. (inaudible) -- the whole reason why EGF-receptor antagonism is contraindicated, typically in RAS-mutant tumors. You really need the RAS inhibitor.

它從根本上解決了 RAS 突變腫瘤中 EGFR 覆蓋不足的整個缺口。（聽不清）——這也是為什麼在 RAS 突變腫瘤中，通常 EGFR 受體拮抗治療是禁忌的根本原因。你確實需要 RAS 抑制劑。

That combination is, in ,principle something that can be pursued. Stay tuned. We'll talk about it when we're able to do so.

原則上，這種聯合用藥是可以推進的。敬請期待。等我們能談的時候會再說。

The question about the first line -- I forgot the tail end of the actual question part of it. It was (multiple speakers) --?

關於一線的問題——我忘了問題最後一段的具體內容。是（多人同時說話）——？

It was: Does it have an interim analysis?

問題是：是否有期中分析？

Oh. Does it have an interim analysis?

喔。是否有期中分析？

Wei, you want to comment on that?

Wei，你要評論一下嗎？

Well, at this current state, we don't plan to disclose the analysis plan.

嗯，就目前這個階段，我們不打算披露分析計畫。

Okay. There, you've heard it from our Chief Medical Officer.

好的。各位已經從我們的首席醫療官那裡聽到了。

Thank you. Thank you.

謝謝。謝謝。

Laura Prendergast, Stifel.

Stifel 的 Laura Prendergast。

:Hey, guys. Thanks for the update.

嗨，各位。謝謝更新。

I was curious: What are some of the top variables still under consideration for daraxonrasib in first-line lung cancer, as far as strategy goes?

我想請教：就策略而言，daraxonrasib 用於一線肺癌，目前仍在考量中的幾個最重要變數是什麼？

On the back of RASolute 302 showing such an unprecedented [OS], what pricing power are you guys thinking that this could unlock? Are there any benchmarks for pricing that you guys are most focused on?

另外，鑑於 RASolute 302 顯示出前所未有的[OS]，你們認為這可能帶來多大的定價能力？你們最關注的定價基準有哪些？

Yeah. Hi, Laura. Nice to hear from you.

是的。嗨，Laura。很高興聽到你的聲音。

Don't think we can really comment on the pricing. Of course, the OS impact is something everybody's interested in, starting with patients and their families and all the way up to insurers and payers in other geographies.

我想我們無法真正評論定價。當然，OS 的影響是每個人都很關心的，從病人及其家屬開始，一直到保險公司以及其他地區的支付方。

It will be relevant to their considerations. But that's about all we could say about pricing today.

這會與他們的考量相關。但就今天而言，關於定價我們大概只能說到這裡。

Your question on first line non-small cell lung cancer, which was what?

你關於一線非小細胞肺癌的問題是什麼來著？

What are the variables we're thinking through?

你們正在思考哪些變數？

Oh, I see, with regard to daraxonrasib in first-line.

喔，我明白了，是關於 daraxonrasib 在一線治療的部分。

We've alluded to it. We commented that there are a couple of things going on. Probably, one of the most important is that we're now dosing patients with ivonescimab, which may become -- we're all waiting to see how that progresses.

我們之前有提到過。我們評論過目前有幾件事同時在進行。可能其中最重要的一點是，我們現在正在讓病人使用 ivonescimab 給藥，而它可能會成為——我們都在等待看它的進展如何。

But it points towards potentially becoming the new standard of care for first-line non-small cell lung cancer; in which case, that's something we need to take into account, which we hadn't really taken into account before we had the real relationship with Summit.

但這指向它有可能成為一線非小細胞肺癌的新標準治療；若是如此，這就是我們必須納入考量的事情，而在我們與 Summit 建立真正的合作關係之前，我們其實並未真正把這點納入考量。

That's now very much active. We're dosing patients. That's probably the main variable.

現在這件事非常活躍。我們正在給病人用藥。這大概是主要變數。

I think the other thing, just conceptually, to comment on is, the mutant-selective inhibitors are already pretty well established simply because of the G12C inhibitors that launched the field.

我想另一點，概念上補充一下：突變選擇性抑制劑之所以已相當確立，主要是因為開創這個領域的 G12C 抑制劑。

That's a paradigm that lung cancer doctors are now used to thinking; that G12C is its own disease, which means G12D will be its own disease and G12V will be its own disease.

這是一種肺癌醫師如今已經習慣用來思考的典範；也就是把 G12C 視為一種獨立的疾病，這表示 G12D 會是它自己的疾病，而 G12V 也會是它自己的疾病。

Pretty quickly, you've covered most of the mutations in RAS lung cancer. We happen to have a G12D-selective inhibitor which is performing particularly well. We happen to have a G12C-selective inhibitor, which is quite differentiated and compelling. We have a G12V-selective inhibitor that's in the clinic now. We expect good things from that.

很快地，你就已經涵蓋了 RAS 肺癌中大多數的突變。我們剛好有一個選擇性抑制 G12D 的抑制劑，表現特別好。我們也剛好有一個選擇性抑制 G12C 的抑制劑，差異化程度很高且很有吸引力。我們有一個選擇性抑制 G12V 的抑制劑，目前已在臨床中。我們對它抱有很高期待。

There are multiple ways to cover that. It is in a field in which it's already broken down by a genotype. That's one possible strategy.

有多種方式可以涵蓋那一塊。這個領域本來就已經按基因型拆分。那是其中一種可能的策略。

Those are several of the major considerations.

以上是幾項主要考量。

Understood. Thank you very much.

了解。非常感謝。

Jay Olson, Oppenheimer.

Jay Olson，Oppenheimer。

Oh. Hey. Congrats on all the progress. Thanks for providing this update.

喔。嗨。恭喜你們取得各項進展。謝謝提供這次更新。

How would you like to set expectations for the upcoming ASCO plenary presentation in terms of where you'd like investors to focus their attention? Thank you.

就即將到來的 ASCO 全體會議（plenary）報告而言，你們希望如何設定市場預期，讓投資人把注意力聚焦在哪些重點？謝謝。

I think my main expectation is, it's going to be crowded. I'm not sure really how to help you on that.

我想我主要的預期是，現場會很擁擠。我不太確定要怎麼在這方面幫到你。

We'll be providing, I think, through the investigators, a full update on it. The update will be consistent with what we've said, so far, but provide significantly more information that the experts in the field need to see and evaluate in that setting.

我想我們會透過研究者提供完整更新。這次更新會與我們迄今所說的一致，但會提供更多資訊，讓該領域的專家在那個場合需要看到並加以評估。

Great. Thank you.

很好。謝謝。

Kelsey Goodwin, Piper Sandler.

Kelsey Goodwin，Piper Sandler。

Hey. Thanks so much for taking my question. Congrats on all the progress, recently. I think, two quick ones from me.

嗨。非常感謝讓我提問。也恭喜你們最近的各項進展。我這邊有兩個簡短問題。

First, I guess any additional color that you're providing on the salesforce.

第一，關於你們在銷售團隊（salesforce）方面是否能提供更多細節。

Secondly, I think, building on one of your prior answers in this question-answer session, as we start to think about that front-line to second-line attrition rate once daraxonrasib comes onto the market, do you have a sense what percent of that 50% of patients that don't proceed to second line are unfit for therapy altogether versus ineligible or unwilling to take another chemotherapy, just as we start to model that out a bit more refined?

第二，延續你們在本次問答中先前的一個回答，當 daraxonrasib 上市後，我們開始思考一線到二線的流失率時，你們是否能判斷：在那 50% 未進入二線治療的病人中，有多少比例是完全不適合再接受治療， versus 因為不符合資格或不願意再接受另一輪化療？我們想把模型做得更精細一些。

Thanks so much.

非常感謝。

Yeah, thanks. Thanks, Kelsey.

好的，謝謝。謝謝你，Kelsey。

Anthony, you want to just comment on the sales organization, more broadly?

Anthony，你要不要更廣泛地談一下銷售組織？

Thanks for the question, Kelsey.

謝謝你的問題，Kelsey。

I think, for the US region, we're in the final stages of building out our field-based teams all across different functions in the field: medical affairs, market access, and sales.

我想在美國地區，我們正處於建立各地外勤團隊的最後階段，涵蓋外勤的不同職能：醫藥事務（medical affairs）、市場准入（market access）以及銷售。

We've had an [MSL] team and a thought leader liaison team in place for quite some time. We also have a market access account team that's been in place. That's been engaging with payers and organized customers, really, around the unmet need in pancreas cancer; around the pipeline and the early clinical data for daraxonrasib through pre-approval information exchanges.

我們的 [MSL] 團隊以及意見領袖聯絡團隊已經建立一段時間了。我們也有已到位的市場准入客戶團隊。該團隊一直在與付款方與組織型客戶互動，主要圍繞胰臟癌的未被滿足需求、我們的產品線，以及透過核准前資訊交換（pre-approval information exchanges）分享 daraxonrasib 的早期臨床數據。

We're really pleased to say that we're in the final stages of onboarding our US. salesforce; that we're pleased with the team. They have deep expertise in solid tumors across [GI] malignancies and in oral oncology. They'll be fully trained and ready to go with HCP engagements, if we were to receive an FDA approval.

我們很高興地表示，我們正處於美國銷售團隊到職（onboarding）的最後階段；我們對這支團隊很滿意。他們在實體腫瘤方面具備深厚專業，涵蓋 [GI] 惡性腫瘤以及口服腫瘤治療領域。如果我們獲得 FDA 核准，他們將完成完整訓練並準備好與醫療照護專業人員（HCP）互動。

Thanks, Anthony.

謝謝，Anthony。

On the first line, the second line, it's a good question. It's an important question. It's a little bit hard to get a detailed and clear understanding of because in reviewing records and so on, it's not always clear.

關於一線、二線，這是個好問題。也是個重要的問題。但要得到細緻且清楚的理解有點困難，因為在回顧病歷等資料時，原因並不總是明確。

In fact, it's surprising how common it is that it's not clear why somebody hasn't gone on to second line. You don't always identify an obvious performance status issue or concurrent illness or disease status that would prevent somebody from moving on.

事實上，令人意外的是，常常不清楚為什麼某位病人沒有進入二線治療。你不一定能辨識出明顯的體能狀態（performance status）問題、合併疾病，或會阻止病人繼續往下治療的疾病狀態。

Therefore, they might have decided not to proceed because of intolerability or they might have decided not to proceed because of perceived intolerability before they tried it or because they want to focus their life at this stage on family and not on chemo infusions. There's a wide variety of reasons.

因此，他們可能因為無法耐受而決定不繼續；也可能在尚未嘗試前就因為預期的不可耐受性而決定不繼續；或是因為在這個階段想把生活重心放在家人，而不是化療輸注。原因非常多元。

And then, sadly, it's also true that patients who start chemotherapy in first line sometimes don't survive to second line. It's a pretty devastating illness, as everybody knows.

然後，令人難過的是，確實也有病人在一線開始化療後，並未存活到能接受二線治療。如大家所知，這是一種相當具毀滅性的疾病。

There are a lot of different reasons. Some of those could be addressed by a regimen that is more convenient; that is better tolerated. A once-a-day pill that really is generally well tolerated and safety issues are manageable could, for sure, impact somebody's decision. We don't know whether or not it will. We'll only know that if we get to the finish line with an approval and see how patients do in that context.

原因很多。其中一些原因可能可以透過更便利、耐受性更好的療程來改善。一顆每日一次的藥丸，整體而言耐受性良好且安全性問題可控，確實可能影響病人的決策。我們不知道是否一定會。只有在我們最終獲得核准並在那樣的情境下觀察病人表現時，才會知道。

Perfect. Thank you so much.

太好了。非常感謝。

Kalpit Patel, Wolfe Research.

Kalpit Patel，Wolfe Research。

Hey. Thanks for taking our questions. Congrats on the trial ahead, (inaudible).

嗨。謝謝回答我們的問題。也恭喜你們接下來的試驗，（聽不清）。

For RASolute 303, how should we think about that study's enrollment ramp versus the second-line study that you just completed in terms of timing of enrollment completion? And then, can you remind us if cross-over is allowed in that RASolute 303 study?

關於 RASolute 303，相較於你們剛完成的二線研究，在入組速度與入組完成時間上，我們應該如何看待這項研究的入組爬坡？另外，可以提醒我們 RASolute 303 研究是否允許交叉治療（cross-over）嗎？

Separately, any comments on potentially starting a registrational trial with daraxon and a PRMT5 inhibitor? Thank you.

另外，對於可能啟動 daraxon 與 PRMT5 抑制劑的註冊性試驗（registrational trial），有任何評論嗎？謝謝。

Thanks very much for your questions.

非常感謝你的提問。

The timing of completion, we can't comment on that now. We're just not at a stage where we can project a timeline with any confidence.

關於完成時間點，我們目前無法評論。我們還沒到能夠有把握地預估時程的階段。

But maybe the even more important point would be we know there's very, very high interest in this. Sites that have activated are enrolling. But there are plenty of sites that still are yet to be online. There are patients lined up at many of these facilities. We're aware of that.

但也許更重要的一點是，我們知道大家對此有非常、非常高的興趣。已啟動的研究中心正在入組。但仍有不少研究中心尚未上線。在許多這些機構，已有病人在排隊等候。我們也注意到這點。

We expect there to be very high demand for this for a variety of reasons, not the least of which is the disclosure of the 302 key findings which elicits people to do it.

我們預期需求會非常高，原因有很多，其中之一就是 302 的關鍵發現已揭露，促使大家想參與。

Cross-over. Cross-over is not allowed in the trial design. As you know, of course, it's up to any individual patient. They can cross over on their own, if there is an approved therapy to cross over to.

交叉治療。試驗設計不允許交叉治療。如各位所知，當然，這取決於每一位個別病人。如果有已核准可轉用的療法，他們也可以自行選擇交叉治療。

In terms of actual cross-over design, we can't really provide it when OS is the standard. That's the conundrum of a Phase I3 trial for which overall survival is the endpoint.

就實際的交叉治療設計而言，當 OS 作為標準時，我們其實無法提供。這就是以整體存活期作為終點的第 I3 期試驗所面臨的兩難。

We're currently in the process of transitioning from equipoise to out of equipoise. Where we stand in that is, it's a matter of judgment and it's really a question for the regulatory agency. They have to make that determination. As long as OS is required, it's very difficult to achieve that with a cross-over design.

我們目前正處於從「均衡狀態（equipoise）」轉向「不再均衡」的過程。我們目前所處的位置，屬於判斷問題，而這其實是監管機關需要回答的問題。他們必須做出該項認定。只要仍要求 OS，就很難透過交叉治療設計來達成。

Do you want to add to those points? No?

你想補充這些重點嗎？不嗎？

The only additional comments I would make, again, because of the concern for overall survival being a primary endpoint is, we've established a broad geographic footprint in order to mitigate the potential for impact of second-line therapy with daraxon, moving forward.

我唯一想再補充的是，同樣因為擔心整體存活期作為主要終點，我們已建立廣泛的地理覆蓋，以降低未來 daraxon 作為二線治療可能帶來的影響。

Smaller US footprint, larger ex-US, moving forward.

未來在美國的覆蓋較小、在美國以外的覆蓋較大。

Right. Good comment.

對。很好的評論。

And then, the last thing was with regard to PRMT5. We don't have any update to provide on that today.

然後，最後一點是關於 PRMT5。我們今天沒有任何更新可提供。

We're enthusiastically engaged in a collaboration with several companies now who are evaluating PRMT5 inhibitors in combination with RAS inhibitors. We're keenly interested in how that work goes.

我們目前正積極與數家公司合作，他們正在評估 PRMT5 抑制劑與 RAS 抑制劑的聯合使用。我們非常關注這項工作的進展。

Alec Stranahan, Bank of America.

美國銀行（Bank of America）的 Alec Stranahan。

Hey, guys. Thanks for taking my questions and for squeezing me in here at the end. Two from me.

嗨，各位。謝謝你們回答我的問題，也謝謝你們在最後把我安排進來。我有兩個問題。

First, would be interested to hear from your experience whether the initial ORR with daraxonrasib was a good metric for predicting PFS and OS benefit in larger studies. Like, does a higher numerical ORR translate to better survival? Or is duration of response or time on therapy maybe more telling for this?

第一個，我想聽聽依你們的經驗，daraxonrasib 的初始 ORR 是否是用來預測在更大型研究中 PFS 與 OS 獲益的良好指標。例如，較高的 ORR 數值是否會轉化為更好的存活？或者反應持續時間或治療時間是否更能說明問題？

Just trying to think through some headline numbers we're seeing from others in the space.

我只是想釐清一下我們從同領域其他公司看到的一些頭條數據。

Quickly, will you be allowing third-line-plus patients into the EAP, as well? Thank you.

另外很快問一下，你們也會允許三線以上的病人進入 EAP 嗎？謝謝。

Thanks, Alec.

謝謝你，Alec。

On the last question, yes, the eligible population includes previously treated. It goes beyond the pure second-line that were in the RASolute 302 trial.

關於最後一個問題，是的，符合資格的人群包含既往已接受治療者。範圍超出 RASolute 302 試驗中純粹的二線治療人群。

Is ORR predictive of PFS or OS? Who wants to comment on that?

ORR 是否能預測 PFS 或 OS？誰想評論一下？

Well, we've done some analysis on that. It's broadly correlative with PFS -- ORR broadly correlates with PFS. It's not such a tight, stocky metric relationship that you can actually say that, if the ORR is 5 percentage points higher, that the PFS is going be 5 percentage points higher. But it is broadly correlated.

嗯，我們對此做過一些分析。它與 PFS 大致呈相關——ORR 與 PFS 大致相關。但這不是那種非常緊密、固定的指標關係，讓你可以說如果 ORR 高 5 個百分點，PFS 就會高 5 個百分點。但它確實大致相關。

There are better ways of predicting PFS (inaudible) -- which involve multi-parametric analyses that include ORR but are not restricted to ORR. We have not made those broadly available to other people because, obviously, it's a competitive advantage for us to know that and not share it with our competitors.

有更好的方式來預測 PFS（聽不清）——涉及多參數分析，會納入 ORR，但不僅限於 ORR。我們沒有把那些方法廣泛提供給其他人，因為很明顯，知道這些而不與競爭對手分享，對我們而言是競爭優勢。

But, definitely, ORR is a component of that framework, for sure. I think, as we're learning more -- and you're right, we're learning a lot more now, now that we have decent drugs for pancreatic cancer. We're learning a lot more about the relationship between all of these outcomes.

但可以肯定的是，ORR 絕對是該框架的一個組成部分。我想，隨著我們學到更多——你說得對，現在我們確實學到更多了，因為我們已經有了對胰臟癌相當不錯的藥物。我們正在更深入了解這些結果之間的關係。

But, in other diseases like lung cancer, breast cancer, and colorectal cancer, it took years and years and years to figure out these relationships. They're still not totally clear.

但在其他疾病，例如肺癌、乳癌與大腸直腸癌，花了很多很多年才逐步釐清這些關係。而且到現在也還沒有完全清楚。

Yeah. I think that you will see relationships emerging, whether they're causal or otherwise. But I wouldn't draw too many straight lines.

是的。我認為你會看到一些關係逐漸浮現，不論它們是否具有因果性。但我不會畫太多直線式的推論。

Yeah. That's a -- I'll pile on on that.

是的。我也補充一下。

There's obviously some relationship. But what you can do with that and how you should interpret ORR data and have vision for what that's going translate into, premature.

顯然存在某種關係。但你能用它做什麼、以及你應該如何解讀 ORR 數據並預見它會轉化成什麼，現在下結論還太早。

Yeah. The other thing is, of course, with RAS inhibitors, the numerical value of ORR at any point in time isn't very accurate anyway.

是的。另外一點當然是，對於 RAS 抑制劑而言，任何時間點的 ORR 數值本身其實也不太精準。

Patients can take up to and sometimes beyond six months to fulfill the RECIST definition of response. At any given point in time, there may still be people who might become responders who have not yet become responders.

病人可能需要長達、甚至超過六個月，才能符合 RECIST 對反應的定義。在任何特定時間點，可能仍有人尚未成為反應者，但之後可能會成為反應者。

The RECIST definition of response isn't a particularly robust endpoint in its own right. There's a lot of wiggle room and uncertainty around all of these analyses.

RECIST 對反應的定義本身並不是特別穩健的終點。在所有這些分析中都有很大的彈性空間與不確定性。

It's very tempting to believe that the overall response rate determined by RECIST is a pure and absolute and accurate measurement. I can tell you it absolutely is not.

人們很容易相信由 RECIST 判定的整體反應率是一個純粹、絕對且精準的量測。我可以告訴你，它絕對不是。

If you look at those CT scans and try to compute the unidimensional measurements of the target lesions, then you'll realize just how fraught with uncertainty the whole thing is.

如果你去看那些 CT 掃描並嘗試計算標的病灶的一維量測，你就會意識到整件事充滿了不確定性。

Alec, I'm glad you asked.

Alec，我很高興你問了這個問題。

Very good. Thank you, guys.

非常好。謝謝各位。

Sorry, Alec. Really hard one.

抱歉，Alec。這題真的很難。

This does conclude the question-and-answer session.

問答環節到此結束。

I'd now like to turn it back to Mark Goldsmith for closing remarks.

接下來我想把時間交回給 Mark Goldsmith 作結語。

Thank you, operator.

謝謝你，接線員。

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

謝謝各位今天的參與，也感謝各位持續支持 Revolution Medicines。

Thank you for your participation in today's conference.

感謝各位參與今天的會議。

This does conclude the program.

本次活動到此結束。

You may now disconnect.

您現在可以掛線。