Revolution Medicines (RVMD) 2026年第三季法說會：RASONQUE銷售額達1.976億美元

重點摘要

• RASONQUE 自 2026 年 8 月 26 日獲得美國 FDA 批准後，在美國商業化上市約五週內創造了 1.976 億美元的產品淨營收。共有超過 5,000 名獨立商業病患接受了治療。
• 早期需求包含自擴展近用計畫（Expanded Access Program）轉換的病患、在用盡現有療法後等待新選擇的病患，以及新符合資格的病患。管理階層提醒，前兩類族群屬於上市初期的有限驅動因素。
• Revolution Medicines 截至 2026 年第三季末擁有 37 億美元的現金、現金約當物及有價證券。該餘額未計入 10 月根據其與 Royalty Pharma 的融資安排所收到的 2.5 億美元。
• 隨著公司擴大臨床研發與商業化營運，第三季研發費用從去年同期的 2.625 億美元增加至 4.171 億美元，銷售、一般及行政（SG&A）費用則從 5,280 萬美元增至 1.533 億美元。
• 該公司重申 2026 全年 GAAP 營業費用財測為 21 億至 22 億美元，其中包括預期的 2.7 億至 2.9 億美元股票型薪酬。
• 管理階層預期，隨著對 RAS(ON) 產品組合及全球商業化基礎設施的投資擴大，2027 全年 GAAP 營業費用將較目前的營運水準增加。

核心財務數據

季末通路庫存不足兩週。管理階層預期長期而言將庫存維持在約兩週的水準。

總額至淨額（gross-to-net）折價處於預期 20% 至 30% 區間的下緣。該公司預期，隨著支付方結構與通路折扣日趨成熟，包括來自 340B 藥價折扣計畫與分銷費用的潛在影響，折價率將在該區間內上升。

業務與營運表現

RASONQUE 上市表現

在美國首發上市涵蓋了超過 5,000 名獨立商業病患，以及約 2,700 名開立處方的醫療保健提供者。約 60% 的使用量來自社區腫瘤診所，40% 來自學術醫療中心，大致反映了這些通路中的病患人數比例。

已報銷的理賠來自合共涵蓋全美胰管腺癌（PDAC）納保人口逾 90% 的健康保險計畫。正式給付政策仍在制定中，病患目前透過既有的保險公司審查程序（包括事前授權與醫療例外申請）獲得治療。

大多數早期病患為先前曾接受過治療的轉移性疾病病患。管理階層表示，初期病患中有相當大的比例為體能狀態較差的晚期病患，這可能導致治療持續時間較短。美國擴展近用計畫的轉換已於 10 月底完成。

NCCN 指南將 RASONQUE 列為第 1 類（Category 1）首選後續治療選項，適用於先前接受全身性治療後復發的局部晚期或轉移性胰臟癌合適病患。這些建議並未改變 FDA 批准的適應症。

國際市場拓展

歐洲藥品管理局（EMA）的人用藥品委員會（CHMP）針對 daraxonrasib 單藥療法發布正面意見，適用於先前曾接受過至少一種全身性治療的轉移性胰臟腺癌成人病患。歐盟委員會的決定目前仍在審議中。

Revolution Medicines 正為歐洲各國層級的健保給付、定價與衛生技術評估（HTA）流程預作準備。該公司亦在推進日本的上市準備工作，具體取決於監管部門的批准。

臨床研發管線

第三期 RASolute 303 研究在美國的受試者招募已經完成，管理階層預期全球招募將於 2027 年上半年完成。該試驗評估 RASONQUE 單藥療法以及聯合化療用於一線轉移性胰臟癌的效果。

該公司已在第三期 RASolute 309 試驗中開始給藥，該試驗評估 RASONQUE 聯合 zoldonrasib 用於一線 RAS G12D 胰臟癌的效果。針對輔助治療的 RASolute 304 以及評估 zoldonrasib 聯合化療的 RASolute 305 亦在進行中。

在非小細胞肺癌方面，RASolve 301 的受試者招募即將結束，所有試驗機構預計於 2026 年 11 月底前截止招募。初步第三期試驗數據預計於 2027 年公布。RASONQUE 在該適應症中仍處於試驗階段。

Revolution Medicines 亦分別啟動了 zoldonrasib 與 elironrasib 聯合療法用於 RAS G12D 及 RAS G12C 一線非小細胞肺癌的研究。

在大腸直腸癌方面，該公司正在啟動第三期 RASonate 312 試驗，以評估 zoldonrasib、cetuximab 以及由試驗主持人選擇的 FOLFOX 或 FOLFIRI。BeOne Medicines 負責出資並執行這項全球註冊臨床試驗。Revolution Medicines 預計將於 2027 年上半年提供早期大腸直腸癌數據更新與第三期試驗設計。

管理階層財測

• 2026 全年 GAAP 營業費用預計仍為 21 億至 22 億美元。
• 財測包含預期的 2.7 億至 2.9 億美元非現金股票型薪酬。
• 管理階層預期，由於對 RAS(ON) 產品組合的投資擴大以及全球商業化基礎設施的拓展，2027 全年 GAAP 營業費用將較目前的營運水準增加。目前尚未提供具體的 2027 年預估區間。
• RASolute 303 的全球受試者招募預計將於 2027 年上半年完成。
• RASolve 301 初步第三期試驗數據預計於 2027 年公布。
• RMC-5127 的初步單藥治療數據預計於 2027 年公布，而 RM-055 的首次人體臨床試驗仍規劃於 2026 年第四季進行。

風險與觀察重點

RASONQUE 前五週的銷售額包含了擴展近用計畫的轉換、初期通路庫存，以及一直在等待新治療選擇的病患。管理階層表示，現在判斷常態化的上市成長軌跡仍為時過早。

早期病患的治療持續時間可能無法代表未來趨勢，因為部分初期病患處於治療後期的階段且體能狀態較差。管理階層預期，隨著上市推展日趨成熟，需求將轉向新符合資格的病患與持續的治療用藥時間。

隨著支付方結構、340B 計畫佔比、分銷費用以及正式保險給付政策的推進，總額至淨額（gross-to-net）折價預計將在 20% 至 30% 區間內上升。

數項主要研發管線計畫仍處於試驗階段，包括 RASONQUE 於非小細胞肺癌及一線胰臟癌聯合療法。歐洲與日本的商業化時程亦取決於監管決策及各國具體的健保准入要求。

分析師問答重點

• 上市組成：管理階層指出了三類早期需求族群：擴展近用計畫轉換病患、等待已獲批療法的病患，以及新符合資格的病患。僅有第三類族群被認為代表較為常態化的需求軌跡。
• 真實世界耐受性：管理階層表示早期醫師與病患的使用體驗良好，但也強調目前上市時間尚短，難以得出具實質意義的結論。
• 保險給付准入：該公司表示，學術機構與社區醫療診所在應對給付要求方面並無實質差異。其給付團隊正為這兩種環境提供事前授權、醫療例外申請及納保流程的支援。
• 一線胰臟癌策略：管理階層表示，對於無化療或含化療方案最終是否能提供更大的長期效益，目前仍持中立態度。目前的第三期試驗計畫評估了 RASONQUE 單藥療法、RASONQUE 聯合 zoldonrasib 以及與化療聯合的方案。
• 大腸直腸癌研發：BeOne 對 RASonate 312 的資助與執行提供了額外的全球研發量能，同時為 Revolution Medicines 釋出內部資源以進行其他研究。管理階層表示，隨著數據陸續公布，大腸直腸癌的研發可能會拓展至最初的 G12D 計畫之外。
• 臨床終點：管理階層強調整體存活期為最具臨床意義的終點。RASolute 303、305 和 309 均將無惡化存活期與整體存活期列為雙重主要終點。

完整法說會逐字稿

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完整財報電話會議逐字稿

管理層陳述

Operator

Good day, and thank you for standing by. Welcome to the Revolution Medicines Q3 2026 Earnings Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded.

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

Ryan Asay

Thank you, and welcome, everyone, to the Third Quarter 2026 Earnings Call. Joining me on today's call are Dr. Mark Goldsmith, Revolution Medicines' Chairman and Chief Executive Officer; Anthony Mancini, our Chief Global Commercialization Officer; Dr. Alan Sandler, our Chief Development Officer; and Jack Anders, our Chief Financial Officer. Dr. Wei Lin, our Chief Medical Officer, will join us for the Q&A portion of today's call.

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 recent periodic report that has been filed with the U.S. Securities and Exchange Commission.

This afternoon, we released financial results for the quarter ended September 30, 2026, and recent corporate updates. The press release and updated corporate presentation are available on the Investors section of our website at revmed.com.

With that, I'll turn the call over to our Chief Executive Officer, Dr. Mark Goldsmith. Mark?

Mark Goldsmith

Thank you, Ryan, and good afternoon, everyone. I'll begin today with several remarks focused on our progress in pancreatic cancer and across our broader RAS(ON) portfolio. Anthony will then provide an update on the initial launch of RASONQUE. Alan will discuss progress across our clinical development programs, and Jack will review our third quarter financial results before I return with brief concluding remarks.

The third quarter marked a transformational period for Revolution Medicines. On August 26, less than 2 years after enrollment began in the global randomized RASolute 302 clinical trial, the FDA approved RASONQUE for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multi-agent systemic therapy, and we immediately began making it available by prescription in the United States.

The approval provided an important regulatory proof point for our RAS(ON) approach and marked the beginning of a new chapter for our company. More importantly, eligible patients and their physicians now have an approved oral targeted medicine designed to directly and broadly inhibit RAS, the main cause of pancreatic cancer in a disease with a profound need for a therapeutic breakthrough. This milestone reflects years of scientific conviction, disciplined development and focused execution by our team and collaborators.

It also formally opens the delivery phase of responsibility for Revolution Medicines. We are working tirelessly to execute the U.S. launch with urgency, help eligible patients access RASONQUE promptly and support a positive treatment experience and rigorously prepare to expand the launch internationally. With the U.S. approval in hand and our execution plan's operational, the foundation in pancreatic cancer is being further reinforced by guideline recognition.

The NCCN Guidelines are more expansive than the approved label and now include RASONQUE as a Category 1 preferred subsequent therapy option for appropriate patients with locally advanced or metastatic pancreatic cancer as well as recurrent disease following prior systemic therapy. In metastatic pancreatic cancer, we believe this guideline placement highlights the strength and relevance to medical practice of RASONQUE and supports the use of RASONQUE in the FDA-approved settings.

Importantly, NCCN's recommendation for treatment in locally advanced disease extends its recommendation beyond the FDA-approved metastatic disease setting, while its first-line metastatic listing recognizes RASONQUE as a Useful in Certain Circumstances option with the applicable category linked to prescribers' assessments of performance status. While these NCCN placements do not change the FDA-approved indication, they reflect NCCN's independent evaluation of the clinical data for RASONQUE in the context of significant unmet needs among patients with advanced pancreatic cancer.

Based on the totality of clinical evidence, we believe RASONQUE is well positioned to become a new global standard of care option for appropriate patients with advanced pancreatic cancer. This progress indicates significant momentum in our pursuit of bold ambitions in pancreatic cancer through a multi-asset strategy designed to extend RAS(ON) inhibition as the core of treatment in earlier lines of therapy and additional disease settings in which RAS is a key cancer driver.

Recent regulatory designations further underscore the momentum. The FDA granted breakthrough therapy designation for the investigational combination of RASONQUE with gemcitabine and nab-paclitaxel in first-line metastatic pancreatic cancer. In addition, the FDA granted orphan drug designation to zoldonrasib for the treatment of pancreatic cancer. We are conducting 4 additional global Phase III studies across first-line metastatic and adjuvant pancreatic cancer, including programs evaluating 2 distinct regimens in first-line RAS G12D pancreatic cancer. Zoldonrasib plus chemotherapy and the novel RAS(ON) inhibitor doublet of RASONQUE plus zoldonrasib.

While each of these regimens remains investigational, together, they reflect our determination to develop multiple potential best-in-class options for patients across the pancreatic cancer continuum. The growing body of evidence is also beginning to drive impact beyond pancreatic cancer. During the quarter, based on promising Phase I/II clinical evidence for RASONQUE in previously treated RAS-mutant non-small cell lung cancer, the NCC guidelines recommended RASONQUE as a Category 2A available targeted agent for patients with metastatic non-small cell lung cancer harboring KRAS G12, G13 or Q61 mutations.

While RASONQUE remains investigational in non-small cell lung cancer, this is an important treatment recommendation in RAS-mutant non-small cell lung cancer where substantial unmet need remains. Later, Alan will provide an update on RASolve 301, a Phase III study of RASONQUE in RAS-mutant non-small cell lung cancer and our broader development strategy in non-small cell lung cancer. We are highly encouraged that the EMA's Committee for Medicinal Products for Human Use, or CHMP, has also moved rapidly to adopt a positive opinion for daraxonrasib as a monotherapy indicated for the treatment of adult patients with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy.

For eligible patients in the European Union living with metastatic pancreatic cancer, a disease where profound unmet need persists, this opinion is a major step towards the potential availability of a new targeted medicine. The unprecedented clinical benefit shown in RASolute 302 provides the foundation for this milestone with superior efficacy versus chemotherapy, along with a manageable safety profile and favorable patient-reported outcomes.

Together with the U.S. approval, the CHMP opinion advances our broader ambition to bring the potential benefits of RAS(ON) inhibition to patients around the world. The European Commission decision remains pending. Anthony will discuss the work underway to prepare for country-level access following a potential approval.

With that, I'll turn the call over to Anthony for an update on the initial launch of RASONQUE and our commercial readiness outside the U.S. Anthony?

Anthony Mancini

Thank you, Mark. The U.S. launch of RASONQUE is off to a strong start. At approval, we outlined 3 priorities: enabling health care providers and eligible patients to achieve a positive treatment experience, ensuring broad coverage and seamless patient access with coordinated support and establishing RASONQUE as a new standard of care for eligible patients with metastatic pancreatic cancer.

Early in the launch, we're encouraged by the progress we're seeing against each of these priorities. RASONQUE generated net product revenue of $198 million for the quarter, reflecting more than 5,000 unique patients treated on a commercial basis. As a reminder, FDA approval occurred on August 26, so these results reflect approximately 5 weeks of commercialization activity.

Demand in the quarter reflected 3 components. First, demand included the transition of patients from our U.S. Expanded Access Program to commercial supply. That transition is now complete for U.S. patients continuing treatment. We prioritized continuity of care and successfully supported patients in obtaining their medication through the transition. Second, separate from the Expanded Access Program transition, early commercial demand included a sizable cohort of patients who had exhausted available treatment options at the time of approval and were waiting for a new treatment option, including patients later in their treatment journey.

And third, following approval, we began serving new eligible patients initiating RASONQUE. We're encouraged by the speed with which we were able to begin serving patients following approval, which reflects the significant unmet need in metastatic pancreatic cancer, the strength of RASONQUE's clinical profile and label, the strong launch readiness and initial execution across functions as well as payer engagement and patient support in line with our expectations.

These early results are highly encouraging. At the same time, with only 5 weeks of commercialization activity, it's too early to draw conclusions about the normalized trajectory of the launch. The Expanded Access Program transition and the initial cohort of patients awaiting commercial availability are finite early launch dynamics. As our launch matures, revenue will increasingly reflect ongoing treatment for newly eligible patients and ongoing treatment duration.

We are also pleased by the breadth of early physician engagement with activation across both academic and community oncology settings and health care providers have responded positively to the RASONQUE data, the approved label and the recent NCCN guideline inclusion. Early payer access has been encouraging. We have strong functional access with RASONQUE claims reimbursed across health plans collectively representing greater than 90% of U.S. PDAC covered lives.

Formal coverage policies are still developing for most plans as would be expected this early in the launch. Our field access and (ON)Path patient services teams are fully operational, supporting benefits verifications, coverage navigation, financial assistance and patient support needs. Their work is central to our goal of helping eligible patients start and remain on treatment as seamlessly as possible.

Overall, we're very encouraged by the early launch experience and by the progress we're seeing across key launch priorities. We remain focused on supporting health care providers and eligible patients, ensuring seamless access and coordinated support and establishing RASONQUE as the new standard of care in metastatic pancreatic cancer.

Following the October 15 positive opinion from the Committee for Medicinal Products for Human Use, or CHMP, we are advancing European launch preparations and country-level reimbursement activities in parallel while awaiting the European Commission decision. The RASolute 302 study provides a strong clinical foundation for our European access plans, including work to support the Joint Clinical Assessment or JCA and National Health Technology Assessment, pricing and reimbursement processes.

Launch time lines will depend on regulatory approval and country-specific access requirements. We expect to be ready to launch as these are met. Subject to regulatory approval, we are also advancing launch readiness work in Japan. With that, Jack will provide additional financial information for the quarter later in the call.

I'll now turn the call over to Dr. Alan Sandler.

Alan Bart Sandler

Thank you, Anthony. RASONQUE's approval provides an important foundation for our deep commitment in pancreatic cancer. At the European Society for Medical Oncology Congress, we presented additional RASolute 302 analyses showing that the overall survival benefit with RASONQUE versus chemotherapy was observed consistently across key patient subgroups, including RAS genotype subgroups, prior treatment settings and preselected chemotherapy regimens.

Overall survival is the most clinically meaningful endpoint in metastatic pancreatic cancer, and these findings reinforce the broad clinical relevance of RASONQUE in the previously treated setting. Our strategy in pancreatic cancer extends well beyond the current approved setting, and we are advancing a broad pancreatic cancer development program across first-line metastatic and resectable disease.

Let's begin with RASolute 303, our global Phase III study of RASONQUE monotherapy and in combination with chemotherapy in first-line metastatic pancreatic cancer. I'm pleased to report that U.S. enrollment is now complete, and we expect to complete global enrollment in the first half of 2027. We are also pleased to have begun dosing patients in RASolute 309, our global Phase III study of the novel RAS(ON) inhibitor doublet of RASONQUE plus zoldonrasib in first-line RAS G12D pancreatic cancer. Taken together with the ongoing RASolute 304 study in the adjuvant setting and RASolute 305 evaluating zoldonrasib plus chemotherapy in the first-line setting, these active studies reflect the breadth and pace of our multi-asset pancreatic cancer Phase III development strategy.

At the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics later this month, we will present longer-term follow-up from the Phase I study of the combination of RASONQUE with gemcitabine and nab-paclitaxel in first-line metastatic pancreatic cancer, building on encouraging data previously reported and further characterizing the regimen's clinical activity and safety profile.

As Mark noted, the FDA's breakthrough therapy designation for the combination of RASONQUE with gemcitabine and nab-paclitaxel in first-line metastatic pancreatic cancer is an important regulatory milestone for that program.

Turning to non-small cell lung cancer. We continue to execute a broad strategy designed to address substantial unmet needs across RAS-driven disease. In RASolve 301, our global Phase III study of RASONQUE monotherapy in patients with previously treated RAS-mutant non-small cell lung cancer, we are winding down global enrollment and expect all sites to close enrollment by the end of the month, positioning us for the planned initial Phase III readout in 2027.

During the quarter, Phase I/II data for RASONQUE in previously treated RAS-mutant non-small cell lung cancer were published in the New England Journal of Medicine, providing peer-reviewed support for the program. As Mark noted, the NCCN guidelines also now include RASONQUE as a Category 2A available targeted agent in the emerging biomarkers table for metastatic non-small cell lung cancer with KRAS G12, G13 or Q61 mutations.

RASONQUE remains investigational in non-small cell lung cancer, and we will continue to advance its development through the RASolve 301 study. We are also advancing our broader first-line non-small cell lung cancer strategy with our mutant selective RAS(ON) inhibitors. We have begun dosing patients in RASolve 308, evaluating zoldonrasib in combination with pembrolizumab and platinum-doublet chemotherapy in first-line RAS G12D non-small cell lung cancer.

We have also initiated RASolve 307, evaluating elironrasib in combination with pembrolizumab and platinum-doublet chemotherapy in first-line RAS G12C non-small cell lung cancer. In colorectal cancer, we are encouraged by the strong clinical activity we've seen in a cohort of patients with RAS G12D colorectal cancer receiving first-line treatment with a combination of zoldonrasib, cetuximab and FOLFOX.

We've observed encouraging objective response rates and disease control rates along with an acceptable safety and tolerability profile that is generally consistent with what would be expected for cetuximab and FOLFOX. We'll need longer follow-up to assess durability.

Nevertheless, we believe the initial clinical profile in this very challenging disease merits a global randomized Phase III trial, RASonate 312 comparing the combination of zoldonrasib, cetuximab and investigators' choice of FOLFOX or FOLFIRI with standard of care. We expect to provide a clinical data update from our earlier phase colorectal cancer studies, along with the RASonate 312 trial design in the first half of 2027.

The RASonate 312 trial is being initiated. Under the agreement we announced earlier this year, BeOne is funding and conducting this global registrational Phase III study on our behalf using its global development superhighway. We are steadfast in our commitment to address this important RAS-driven cancer and the needs of this underserved patient population. In our earlier-stage pipeline, RMC-5127, our RAS(ON) G12D selective inhibitor, continues in its first-in-human study. We are in the late stages of identifying a candidate recommended Phase II dose, and we expect to share initial clinical monotherapy data in 2027.

Finally, RM-055, our first mutant targeted catalytic RAS(ON) inhibitor remains on track for initiation of its first-in-human clinical study in the fourth quarter. Taken together, the progress across our pipeline reinforces the breadth of our RAS(ON) platform and our opportunity to build multiple important medicines for patients with RAS-driven cancers. Beyond the programs we sponsor directly, we are collaborating with leading academic institutions and investigators to advance a robust externally sponsored research program.

Studies that Revolution Medicines supports through this program enable independent investigators to explore our RAS(ON) inhibitors in additional scientifically compelling settings and populations with significant unmet medical needs, including but not limited to pancreatic and other gastrointestinal cancers. This program provides another avenue to build evidence across RAS-driven cancers and underscores the breadth of interest in our pipeline.

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

Jack Anders

Thanks, Alan. The third quarter of 2026 represented our first quarter as a commercial-stage company following the U.S. approval of RASONQUE. RASONQUE generated net product revenue of $197.6 million during the quarter. This reflects a partial quarter and also includes initial stocking of inventory into the channel. We ended the quarter with less than 2 weeks of inventory in the channel and in the long run, expect to manage channel inventory at approximately 2 weeks.

The gross-to-net discount for the quarter came in at the lower end of our anticipated 20% to 30% range. We are early in the U.S. launch, and as payer mix and discounts evolve and mature, we expect the gross-to-net discount to increase within that anticipated range. Cost of sales for the quarter was $0.3 million. This amount should not be viewed as representative of normalized cost of sales as products sold during the quarter includes product manufactured before FDA approval, which was previously expensed to R&D.

Turning to our capital position. We ended the third quarter with $3.7 billion in cash, cash equivalents and marketable securities. This balance does not include an additional $250 million in proceeds received after the quarter relating to the first debt tranche under our funding arrangement with Royalty Pharma.

The approval of RASONQUE triggered 2 separate financing tranches under the agreement, a mandatory first debt tranche, which we received in October and an optional third royalty tranche. We elected not to draw the optional third royalty tranche given our strong cash position as taking the optional tranche would have committed us to pay incremental future royalties under the funding arrangement.

There remains up to an additional $1 billion in committed capital under the funding arrangement, subject to the achievement of specified milestones, all of which is optional and at our election to draw. Our financial position continues to provide the flexibility to support the U.S. launch of RASONQUE, our continued global commercialization build-out and the broad advancement of our RAS(ON) inhibitor portfolio.

Moving to expenses. R&D expenses for the third quarter of 2026 were $417.1 million compared to $262.5 million for the third quarter of 2025. The increase in R&D expenses was primarily driven by higher clinical trial and manufacturing expenses for RASONQUE, zoldonrasib and RMC-5127, increased personnel-related costs due to additional headcount and higher stock-based compensation expense.

SG&A expenses for the third quarter of 2026 were $153.3 million compared to $52.8 million for the third quarter of 2025. The increase in SG&A expenses was primarily driven by higher personnel-related costs associated with additional headcount, higher commercial expenses associated with the RASONQUE commercial launch and higher stock-based compensation expense.

Net loss for the third quarter of 2026 was $407.5 million compared to $305.2 million for the third quarter of 2025. Net loss for the third quarter of 2026 included a noncash charge of $40.7 million related to a change in the fair value of warrants we assumed as part of our EQRx acquisition. This charge related to an increase in our stock price during the quarter.

Turning to financial guidance. We are reiterating our guidance for full year 2026 GAAP operating expenses of $2.1 billion to $2.2 billion. This includes expected noncash stock-based compensation expense of $270 million to $290 million. As we turn to 2027, we expect to increase our investments in advancing our broad RAS(ON) inhibitor portfolio and also expect to increase our commercialization efforts, including expanding our global commercialization infrastructure. While we are not providing a specific range at this time, we do expect full year 2027 GAAP operating expenses to increase from our current GAAP operating expense run rate. That concludes the financial update.

I'll now turn the call back over to Mark.

Mark Goldsmith

Thank you, Jack. Before we open the call for questions, I'd like to briefly highlight 2 collaborations that further support our long-term strategy. During the quarter, we announced a multipart collaboration with BeOne Medicines that expands both our combination development capabilities and our regional commercial reach. The clinical development component will evaluate novel combination approaches involving select BeOne oncology assets and assets from among our 4 clinical-stage RAS(ON) inhibitors, including RASONQUE. Under a separate regional rights agreement, BeOne holds exclusive development and commercialization rights for these 4 assets in select Asian markets.

Importantly, as referenced earlier by Alan, BeOne is also funding and conducting on our behalf, a global registrational Phase III study of zoldonrasib, RASonate 312 in first-line RAS G12D colorectal cancer. This brings significant additional development capability into play as we continue to execute our broad global portfolio strategy. In October, we also entered into clinical collaborations with Bristol Myers Squibb to evaluate pumitamig, an investigational PD-L1/VEGF bispecific antibody in 4 planned early-stage combination study cohorts across our portfolio of RAS(ON) inhibitors.

Pumitamig is an investigational PD-L1/VEGF bispecific immunomodulator jointly developed by BioNTech and Bristol Myers Squibb. The planned cohorts include RASONQUE in non-small cell lung cancer and pancreatic cancer, elironrasib in non-small cell lung cancer and zoldonrasib in colorectal cancer. We will provide additional details as the cohorts are initiated.

Our collaboration with Summit on ivonescimab, the first member of this class of bispecific inhibitors to enter clinical development remains fully active and productive. Together, these collaborations are components of our larger deliberate strategy to build development capacity, expand the reach of our medicines and evaluate rational combinations that may further improve outcomes for patients with RAS-addicted cancers.

Stepping back, we are proud of the robust activities and broad progress spanning all aspects of our discover, develop and deliver model on behalf of patients. That includes an encouraging initial phase of the U.S. commercial launch of RASONQUE with its compelling product profile, addressing serious unmet needs with strong progress toward entering international markets. A broad portfolio of pivotal trials with our first 3 clinical RAS(ON) inhibitors in 3 major RAS-driven tumor types, the RASolute Phase III series in pancreatic cancer, the RASolve Phase III series in non-small cell lung cancer and the RASonate Phase III series in colorectal cancer.

Exciting clinical collaborations exploring additional combination strategies as well as external research pushing the boundaries, building clinical momentum with our fourth RAS(ON) inhibitor and a pending first-in-human study of our fifth that represents a new class of inhibitors. And a maturing collection of innovative preclinical programs and assets that are continuously informed by our vast scientific and clinical experience in RAS-driven cancers.

Looking ahead, our priorities are clear: deliver RASONQUE with urgency to eligible U.S. patients with metastatic pancreatic cancer and prepare for potential commercial availability in Europe and Japan; advance our multi-asset clinical development strategy across pancreatic cancer, non-small cell lung cancer, colorectal cancer and other RAS-driven cancers; deliver the next wave of clinical milestones, including an update on our colorectal cancer program while continuing to advance our earlier-stage RAS(ON) pipeline.

RASONQUE's approval and launch mark a monumental step forward for patients living with RAS-dependent cancers and open an important new chapter for Revolution Medicines. With this momentum, we continue our deep commitment to discovering, developing and delivering innovative targeted medicines with the urgency patients deserve.

With that, I'll turn the call over to the operator for questions.

Operator

[Operator Instructions] Our first question comes from Charles Zhu at LifeSci Capital.

分析師問答

Yue-Wen Zhu

Congratulations on your first partial quarterly sales and on all the progress as always. Maybe first on that quarterly sales figure. Are you able to provide some, sort of, high-level breakdown of some commercial patients, whether it's by line of therapy, dynamics related to treatment beyond progression? Basically, how has duration of treatment looked in the real world relative to your experience with RASolute 302 and the EAP?

Mark Goldsmith

Thanks a lot, Charles. Anthony?

Anthony Mancini

Yes. Thanks for the question, Charles. I think as I described in my prepared remarks, there are really 3 cohorts of patients described in the demand in this early phase, the EAP patients, several -- a good percentage of those EAP patients will have received several months of therapy before transitioning to commercial product. The patients who had exhausted available treatment options who are really awaiting an approved treatment. Those 2 treatment cohorts are finite as we outlined. We're not providing detail -- the detailed breakdown of those.

But what we can say is that a meaningful portion of those initial patients are later-stage patients that are lower performance status and as a result, may have shorter treatment durations. The third cohort, though, that we described really would represent, kind of, more of a normal demand trajectory. So they're really newly eligible patients on RASONQUE following approval, and we expect to see duration of therapy follow a duration that's more in line with our expectations in the clinical trial.

I think I'll leave it there, Charles. Thanks for the question.

Operator

Our next question comes from Tyler Van Buren at TD Cowen.

Tyler Van Buren

Congratulations on a historic first-month sales result. As we think about the trajectory for patients going on RASONQUE therapy moving forward and the over 5,000 patients starting commercial treatment, can you help us quantify, I guess, the amount of stocking in the $198 million sales number?

Jack Anders

Thanks for the question, Tyler. We said in our prepared remarks that the channel inventory, which is the stocking. We ended the quarter with less than 2 weeks of inventory in the channel. And on a go-forward basis, more long term, we'd expect to manage that level at around 2 weeks.

Operator

Our next question comes from Michael Schmidt at Guggenheim.

Michael Schmidt

Congrats on all the momentum in recent months. I had a question on colorectal cancer. So exciting to see the RASonate 312 study up and running now in frontline CRC with zoldonrasib. And I'm just curious how you think about the colorectal cancer opportunity in a broader sense. Do you see opportunity, for example, for a chemo-free option similar to what you're doing in pancreatic cancer? And how do you think about addressing some of the other KRAS mutation subsets longer term?

Mark Goldsmith

Yes. Thanks, Michael. I think that the scope of our CRC program will evolve over time. We're very committed to colorectal cancer. And so the 312 study is really just the first. We certainly don't expect it to be the last of the late-stage development programs. All of those decisions will be data-driven as the 312 study was as well. So I'd just say stay tuned. This is an area that will require significant investment over time. We'll continue to generate data across various combination strategies.

With regard to mutations beyond G12D, we certainly have high interest even though G12D is the most common mutation in colorectal cancer, G12V is the second most common. And of course, RMC-5127 is working its way through the dose escalation and RP2D evaluation. So stay tuned. We'll be working to cover as much of the colorectal cancer space as we can and to move -- to keep working towards early lines of therapy in order to have the greatest impact on behalf of patients.

Operator

Our next question comes from Andrea Newkirk at Goldman Sachs.

Andrea Tan

Congratulations on the quarter. I'm just curious if you're able to share how uptake has been split across community oncology networks versus the academic centers. And have you noticed any differences in prescribing velocity across the 2 settings?

Mark Goldsmith

Thank you, Andrea. Nice to have you back, Anthony?

Anthony Mancini

Yes. Thanks for the question, Andrea. We're really encouraged by the breadth of interest and the early uptake across both the academic cancer centers and the community oncology practices. But what I'll add is approximately 2,700 unique health care providers prescribed RASONQUE in the quarter. And the utilization across the academic and community settings was representative of the overall patient volume. So it was about a 40% academic contribution and about a 60% community contribution.

So we're really pleased with that. Our focus is to continue to educate health care providers and particularly as we build familiarity in the community practice, our goal is to create a positive patient and customer experience. And that really is all about understanding the label, understand the safety profile and really being aware of all the resources available to help eligible patients start on RASONQUE and stay on RASONQUE.

Operator

Our next question comes from Cory Kasimov at Evercore ISI.

Cory Kasimov

Yes, definitely great to see such an impressive start to the launch. So I -- look, I understand this might be tough to answer. I want to ask about the launch maybe from a different angle. But again, with over 5,000 patients receiving commercial RASONQUE in the first 5 weeks, can you, kind of, at least qualitatively comment on what you're seeing in October that might be able to help distinguish the initial backlog from, kind of, sustainable new patient demand?

Mark Goldsmith

I'll ask Anthony to deliver the disappointing news.

Anthony Mancini

No, Cory, thanks for the question. I think we're 5 weeks into the launch in the quarter. One of the things that has happened in October is the EAP program has officially wound down. And so we know that all of our EAP transitions have been completed by the end of this month. I think adding additional color probably at this time without the full quarter probably isn't going to be a helpful exercise. So we'll leave it there.

Operator

Our next question comes from Sean Laaman at Morgan Stanley.

Hyunji Sun

This is Katherine on for Sean. Congrats on the strong start to launch. Given that it's early, but could you please share some feedback you've been hearing about RASONQUE tolerability in the real world now that use is moving more into the community? Do you have any feedback on how physicians are managing the toxicities with either the prophylaxis or the education materials you mentioned? Any color here would be appreciated.

Mark Goldsmith

Is there anything that you want to comment on there? Anthony? Do you want to start and I'll...

Anthony Mancini

Maybe I'll comment in general that our experience thus far has been very positive. We have spent a considerable focus and attention on ensuring the education around our adverse event profile. So far, so good is what I would say. I think our plans are coming to fruition. The reactions have been positive to date. But again, it's very early. So we're really focused on ensuring a positive customer experience. And so far, so good is what I would say. There's really not a lot to add at this point, but I'll have a lot more to report with a full quarter [indiscernible] . Thanks for the question.

Operator

Our next question comes from Brian Cheng at JPMorgan.

Lut Ming Cheng

Congrats on the first print, very impressive out of the gate. You talked about NCCN guideline has a very broad usage recommendation, including locally advanced patients. I'm curious if you're starting to see that in this initial wave that you're seeing? And then second, on colorectal. I think you talked about how BeOne will be funding and conducting the study on RevMed's behalf. Can you provide a little bit more color on that decision to lean on BeOne here? Why not just run the colorectal data -- colorectal trial yourself?

Mark Goldsmith

You want to comment on the NCCN?

Anthony Mancini

Yes. Thanks, Brian, for the question. Right now, what I can comment on is that the majority of patients that we're seeing are metastatic PDAC patients that are previously treated. At this point, given their small numbers, I mean, there likely are some locally advanced patients and some frontline patients, but it's the majority is certainly in the later stages at this point.

Mark Goldsmith

Yes, Brian, with regard to CRC, I think your question related to the funding and conduct of the 312 trial and why BeOne. Well, we established a relationship with them earlier this year, a multipart collaboration. And part of that collaboration included their commitment of the resources, the person power, the global footprint to conduct one Phase III trial on our behalf and at their cost, which was essentially in exchange for certain commercial rights that they would obtain.

So this is simply part of a multilevel collaboration. It's an economic benefit to us, but it also takes advantage of a very high-quality global development capability that complements ours. We have similarly been developing that capability, but this adds bandwidth and it frees up our internal resources to continue to conduct other studies and to open up new lines of investigation. So it's a win for us, and we're very pleased and actually quite excited that they're moving forward with it, and they're initiating that study as we speak.

Operator

Our next question comes from Faisal Khurshid at Jefferies.

Faisal Khurshid

I wanted to ask -- so there's other companies in the space, those that have G12D inhibitors that have said that they think they can support filing in frontline pancreatic cancer based on overall response rate. Could I ask you to comment on this and whether this is a strategy you think that you can pursue with your frontline pancreatic studies?

Mark Goldsmith

Yes. Thanks a lot. Well, I guess there's a 2 parts. Is that a question we -- is that an opportunity we could pursue or want to pursue? Or are we pursuing it? Alan?

Alan Bart Sandler

Yes. Thanks for the question. So I think there's a number of different ways to, again, look at drug development. And of course, overall survival remains the most clinically meaningful endpoint and most important the overall benefit risk. And what I'd also like to say, this was established, of course, in RASolute 302 with RASONQUE. Importantly, RASolute 303, 305 and 309 already include PFS and OS as dual primary endpoints. So these are also well underway in their conduct.

With respect to ORR, it's certainly unclear that, that is an endpoint that can stand on its own and typically, historically has always been associated with an additional durability endpoints such as PFS and OS, which I just commented upon and stated that our studies have already incorporated that in. So I think we have a very robust approach, and we'll be in discussions with the FDA appropriately as data comes forward.

Operator

Our next question comes from Michael Yee at UBS.

Michael Yee

I was going to ask on November sales, but I think you're not going to talk to that, Mark. It's been a weekend in November. But instead, actually, there's a lot of development going on in PRMT5. You make a bunch of comments at the bottom about how you have collaborations. And also in August, you did one with BeOne.

Can you maybe just talk a little bit about the different assets that you're partnering with? And how to think about that since that is a big part of pancreatic? Pan-RAS, obviously, is the, sort of, the backbone and how we should think about whether you could either bring one in or just choose to collaborate and hopefully, all the different companies have a different shot at it.

Mark Goldsmith

Yes. Thank you, Michael. Well, we certainly recognize the encouraging clinical data that were generated by Tango as has the field that essentially provides proof of concept for the field. And I think there's no doubt that there will be continued investigation of PRMT inhibition in combination with RAS multi inhibitors or various other, I mean, selective inhibitors. And we certainly share the goal of advancing promising regimens for patients as quickly as possible.

As you point out, we're currently evaluating 3 PRMT5 inhibitors. We had 4. One of those was from Amgen. That program was discontinued, but we now have 3, Tango, of course, BMS and BeOne -- and each of those has a somewhat different profile. I don't think it's -- would be meaningful for me today to try to highlight what those features are because that will ultimately be proven out through extensive clinical evaluation in the combinations. But they do have distinct pharmacologic features, and we'll see how all of that goes.

We think it's very attractive and very serving of patients' interest to have those multiple studies underway for us to have an opportunity to see how they all perform relative to each other. As to whether or not we would bring in a PRMT5 inhibitor into our shop, well, I guess, first, I probably wouldn't tell you if that's something we did want to do, and I wouldn't tell you if that's something we didn't want to do. So I just really can't answer that. We do think that the community, the world is being served by the studies that are underway now, but that would ultimately just be a business or strategic question for us to make at any given point in time.

Operator

Our next question comes from Asthika Goonewardene at Leerink.

Asthika Goonewardene

My congratulations as well for an outstanding quarter here. Just to tag on to Brian's question, can you talk to us a little bit about maybe the restrictions that the payers may be putting up against off-label but [ on-compendia ] use? And if I can also ask, are community centers dealing with the prior authorizations and the restrictions as well as the academic counterparts?

Mark Goldsmith

Okay. Thanks for those questions. Anthony?

Anthony Mancini

Yes. Thanks, Asthika, for the questions. So far, look, as we said, there have been reimbursed claims across health plans that collectively represent greater than 90% of U.S. PDAC covered lives. What that means is really we have strong functional access and patients are gaining access through established payer review processes. So medical exception prior auth in advance of formal coverage policies. Now we have a full field-based reimbursement team that's assisting both the academic setting and the community setting with navigating those things.

That's going really, really well. But in this period of time before formal coverage policies, it's -- there are claims that are reimbursed that may not get reimbursed post coverage policies. It's just a period of time that in -- that we're in right now. But this is what we've expected, and we expect to continue to work on ensuring that the various payers have what they need at P&Ts that are coming up. But yes, there's no big differences, and we're not seeing anything unexpected at this point, Asthika.

Operator

Our next question comes from Jay Olson at Oppenheimer.

Jay Olson

Congratulations on a stellar launch. Could you describe any trends you're seeing in the typical profile of patients who were treated with RASONQUE in the first-line setting? And any anecdotal feedback from prescribers on how patients are responding to therapy? And maybe how those responses might influence their future decisions about treating patients in the first-line setting.

Mark Goldsmith

Jay, those are great questions. I think it's just too early to have any information that would be meaningful at this point. I think as we see more patients treated over time and for longer duration, I think those sorts of concepts will start to emerge.

Operator

Our next question comes from Gregory Renza at Truist Securities.

Gregory Renza

Mark, congrats on an excellent quarter. I just wanted to ask on the PD-1/VEGF strategy and perhaps on the partner breadth that you're pursuing. And maybe at first blush, the Bristol collaboration may appear in maybe greater scope than perhaps the ivonescimab combo.

I just wanted to ask how this, sort of, fits into the broader strategy? And if you could just comment on the scope that we are maybe observing on the Bristol versus the ivonescimab collaboration.

Mark Goldsmith

Yes. Thanks, Greg. I'm not sure that that's -- that we would necessarily see it that way. They're both pretty broad collaborations. There's both high interest by both of those parties. These compounds are not identical, of course. One is focused on PD-1 -- on the PD-1 axis and the other is a PD-L1 component on the PD-1 axis. Those may or may not have differences. I just think it's just far too early to tell. And we're excited to be -- we were the first to be combining RAS inhibitors with a bispecific.

Now we're the second to be combining RAS inhibitors or RAS(ON) inhibitors specifically with the bispecific. And this is part of a broad approach. We've got a very big footprint in the field in the industry now. And this is the best way for us to maximize assessment of the potential value of our compounds in various context in these very important diseases.

Operator

Our next question comes from Laura Prendergast at Stifel.

Laura Prendergast

Congrats on the very exciting start to the launch. I just want to get some expectations for upcoming data sets. First, what should we expect from the late-breaker abstract at Triple ENA meeting? Could we get PFS, OS Kaplan-Meier curves here? And then as far as the colorectal cancer data in first half of '27, will this strictly be supportive of the regimen you're bringing forward in this BeOne collaboration trial? Or would we maybe see a broader array of CRC data you've generated here?

Mark Goldsmith

Yes. Thank you, Laura. Generally, we don't give that level of resolution of guidance about future disclosures. I think Alan already pointed out in his prepared remarks that the ENA presentation would, kind of, reinforce the -- our understanding of the profile of that combination as to what exactly will be included. That's something that will be revealed when the presentation is made.

And similarly, with CRC, I think that our commitment has always been that we would provide the data supporting a decision to move forward. And sometimes we provide those data well ahead of initiating trials. Sometimes we provide it right at the time of launching a trial. And in this particular case, we'll provide it a little bit after the initiation of the trial. But as to exactly what's the scope of that disclosure, unfortunately, it's our practice not to -- and as you know, we've had this conversation before, it's our practice not to preview that in advance.

Operator

Our next question comes from Alex Stranahan at Bank of America.

Alec Stranahan

Big congrats on the early uptake and excited to see where the launch goes from here. Just on that 20% to 30% gross-to-net with the early dynamics being towards the low end of the range, like you said, I guess, could you talk about how payer mix is tracking versus your expectations? And which segments are maybe expected to grow as you see that gross-to-net normalizing over time?

Jack Anders

Yes. So we did note that we expect it to increase within that range as the payer mix and discounts, kind of, evolve and mature. I would say largely from an expectation perspective on a go-forward basis, as we think about, kind of, channel discounts, those are the ones that we would probably expect a little bit more to affect the gross-to-net discount. So we're talking [ 340B ], some potential distribution fees that we may be paying within the channel. But so that's how we're thinking. It's still very, very early in the launch, and we'll get more information as we go along, but that's, kind of, our -- how we're viewing it at this time.

Operator

Our last question comes from Sean McCutchen at Raymond James.

Sean McCutcheon

I'll send my congrats as well. We've continued to hear chemo-free therapy -- a chemo-free regimen is a priority for KOLs. Can you speak to the strategic import of a chemo-sparing frontline regimen in PDAC for you? And one of your competitors, your G12D competitors announced plans for an arm of their frontline study combining with EGFR antibody. I'd love to get your thoughts on how you're positioned with the dual RAS approach in that context.

Mark Goldsmith

Yes. Well, maybe I'll make a conceptual comment and then just a concrete point. The conceptual comment is that I think it's unclear, and we've had this position for several years now, whether an early chemo-free approach ultimately delivers the greatest long-term benefit or whether combining with chemo would deliver more value. We're very neutral on this point. And I think it's a debate that's been around in the oncology field for a long time, and it comes down to, sort of, just empirically evaluating it. There's no theoretical way to differentiate or to rank or prioritize those.

I think the second comment is, I think we've got the first chemo-free first-line regimen and the second first-line chemo-free regimen already well underway. The 303 trial already has an arm that's daraxonrasib alone. And even though the FDA has already approved, daraxonrasib for first-line use under -- when it's at the discretion of physicians based on candidacy for other treatments. So that's one.

And then secondly, we've combined daraxonrasib with zoldonrasib in our 309 trial, and that is moving forward as well. So we're evaluating that. We're evaluating in combination with chemo. We're evaluating daraxonrasib in combination with chemo, zoldonrasib in combination with chemo. I think we've got a lot going on there, but it's still TBD how those will all perform relative to each other.

Operator

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

Mark Goldsmith

Well, thank you, operator, and thank you to everyone who joined us today and for your continued interest in Revolution Medicines. We appreciate the continued support of our shareholders, collaborators, investigators and above all, the patients and families we serve.

Operator, you may now conclude the call.

Operator

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