Verastem Inc (VSTM) 2026 Q1 法說會逐字稿

Good afternoon, and welcome to Verastem Oncology's first-quarter 2026 earnings conference call. My name is Daniel, and I will be your call operator today. Please note this event is being recorded. (Operator Instructions)

下午好，歡迎參加 Verastem Oncology 2026 年第一季財報電話會議。我叫 Daniel，今天將擔任電話會議接線員。請注意，本活動將被錄音。(接線員指示)

I will now turn the call over to Julissa Viana, Vice President of Corporate Communications, Investor Relations and Patient Advocacy for Verastem Oncology. Please go ahead.

現在我將把電話交給 Verastem Oncology 企業傳播、投資人關係與病患倡議副總裁 Julissa Viana。請開始。

Thank you, operator. Welcome, everyone, and thank you for joining us today to discuss Verastem's first-quarter 2026 financial results and recent business updates. This afternoon, we issued a press release detailing these results, along with a slide presentation that will be referenced during our call today. Both are available on the Investor Relations section of our website.

謝謝，接線員。各位好，感謝各位今天加入我們，一同討論 Verastem 2026 年第一季財務結果與近期業務更新。今天下午，我們已發布新聞稿，詳述這些結果，並提供一份簡報投影片，將在今天的電話會議中引用。兩者皆可於我們網站的投資人關係專區取得。

Before we begin, let me point out that we'll be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially. We encourage you to consult the risk factors discussed in our SEC filings for additional detail.

在開始之前，我先提醒各位，我們將發表以前瞻性陳述為主的內容，這些陳述係基於我們目前的預期與信念。此類陳述受若干風險與不確定性影響，實際結果可能出現重大差異。我們建議各位參閱我們向 SEC 提交文件中所討論的風險因素，以取得更多細節。

Additionally, today, we will be discussing certain non-GAAP financial measures. Reconciliations to the most directly comparable GAAP measures are provided in the press release we issued today.

此外，今天我們也將討論若干非 GAAP 財務衡量指標。與最直接可比之 GAAP 指標的調節表已載於我們今天發布的新聞稿中。

Joining me on today's call to deliver prepared remarks and take your questions are Dan Paterson, President and CEO; Dr. Michael Kauffman, President of Development; and Dan Calkins, Chief Financial Officer.

今天與我一同出席、將發表準備好的談話並回答各位提問的有：總裁暨執行長 Dan Paterson；研發總裁 Michael Kauffman 博士；以及財務長 Dan Calkins。

I will now turn the call over to Dan.

現在我把電話交給 Dan。

Thank you, Julissa. Good afternoon, and thank you for joining our call today.

謝謝你，Julissa。下午好，感謝各位今天加入我們的電話會議。

Tomorrow marks one year since the accelerated approval of AVMAPKI FAKZYNJA CO-PACK, a practice-changing medicine approved for patients with KRAS-mutated recurrent low-grade serous ovarian cancer. Since our launch in May 2025, we've seen steady growth quarter over quarter, achieving $18.7 million in net product revenue in Q1 with nearly $50 million in total net product revenue to date.

明天是 AVMAPKI FAKZYNJA CO-PACK 獲得加速核准滿一週年；這是一項改變臨床實務的重要藥物，核准用於 KRAS 突變之復發性低度漿液性卵巢癌患者。自 2025 年 5 月上市以來，我們看到營收逐季穩健成長，第一季淨產品營收達 1,870 萬美元，迄今累計淨產品營收接近 5,000 萬美元。

While we're pleased with the growth we've seen, we believe there's meaningful opportunity to build on the foundation we've established. New patient starts remain consistent month-over-month. Our prescriber base continues to grow and the reimbursement environment is favorable.

雖然我們對目前看到的成長感到滿意，但我們相信仍有相當大的機會在既有基礎上再接再厲。新病患起始用藥人數月對月維持一致。我們的開立處方醫師基礎持續擴大，且給付環境有利。

As part of our ongoing commitment to optimize our launch, we conducted a focused review of our launch performance and execution and implemented targeted changes to our commercial organization and leadership. I'll walk through these details in a few minutes. I want to underscore that our confidence in the underlying demand and overall opportunity for the CO-PACK remains unchanged.

作為我們持續致力於優化上市推進的一部分，我們針對上市表現與執行進行了聚焦式檢視，並對商業組織與領導團隊實施了具針對性的調整。我將在幾分鐘後說明這些細節。我想強調，我們對 CO-PACK 的基本需求與整體機會的信心仍然不變。

Moving to R&D. We've made significant progress with our clinical trials for VS-7375, our potential best-in-class oral and selective KRAS G12D ON/OFF inhibitor, now branded as the VS-7375 Target-D clinical trial program. The Target-D-101 Phase 1/2 dose escalation and expansion trial is already underway, and we continue to enroll patients and evaluate higher dose levels.

接著談研發。我們在 VS-7375 的臨床試驗方面取得重大進展；VS-7375 是我們潛在同類最佳（best-in-class）的口服且具選擇性的 KRAS G12D ON/OFF 抑制劑，現以 VS-7375 Target-D 臨床試驗計畫為品牌。Target-D-101 第 1/2 期劑量遞增與擴展試驗已在進行中，我們持續收案並評估更高劑量層級。

In addition, we've also initiated our Phase 2 registration-directed clinical trials in second-line pancreatic cancer, second and third-line non-small cell lung cancer and second-line plus metastatic colorectal cancer. Michael will share more about our progress and strategies with these trials. We continue to closely manage our expenses and remain on track for the LGSOC franchise to be self-sustaining in the second half of the year, meaning CO-PACK revenues will support both commercial operations and any ongoing clinical trials for avutometinib plus defactinib. As we look to the balance sheet, our focus remains on identifying value-creating non-dilutive opportunities as we advance our pipeline and deliver for patients and shareholders.

此外，我們也已啟動第 2 期、以註冊申請為導向的臨床試驗，涵蓋二線胰臟癌、二線與三線非小細胞肺癌，以及二線以上之轉移性大腸直腸癌。Michael 將分享這些試驗的進展與策略。我們持續嚴格控管費用，並仍按計畫在今年下半年讓 LGSOC 產品線達到自給自足，也就是 CO-PACK 的營收將可支應商業營運以及任何正在進行的 avutometinib 加 defactinib 臨床試驗。就資產負債表而言，隨著我們推進產品線並為病患與股東交付成果，我們的重點仍是尋找能創造價值、且不具稀釋性的機會。

With that, let me turn to our commercial update. With almost a year into the launch, we're continually monitoring our progress. As with any launch, there's a natural evolution as we learn more about the market dynamics. We took a comprehensive look at our commercial execution and have taken decisive actions to strengthen it and position the business for the next phase of growth.

接下來，我來更新商業進展。上市將近一年，我們持續監測進度。如同任何產品上市推進，隨著我們更了解市場動態，過程中會有自然的演進。我們全面檢視了商業執行，並採取果斷行動加以強化，讓業務能為下一階段成長做好定位。

Most notably, we've appointed a new Chief Commercial Officer, Dan Lyons, who has deep and relevant experience in oncology and rare diseases. He has a strong track record of leading global commercialization strategies across solid tumor cancers, including two successful rare disease and oncology launches at SpringWorks. Dan's leadership will be instrumental as we evolve our launch and bring AVMAPKI FAKZYNJA CO-PACK to all patients who could benefit from this important treatment. While Dan will not be joining us on the call today, he's already actively engaged with the team driving new and existing initiatives forward.

最值得一提的是，我們任命 Dan Lyons 為新任商務長（Chief Commercial Officer），他在腫瘤與罕見疾病領域具備深厚且高度相關的經驗。他在實體腫瘤的全球商業化策略領導方面有亮眼成績，包括在 SpringWorks 成功主導兩項罕見疾病與腫瘤產品上市。隨著我們推進上市策略演進，並將 AVMAPKI FAKZYNJA CO-PACK 帶給所有可能受益於此重要治療的病患，Dan 的領導將扮演關鍵角色。雖然 Dan 今天不會加入電話會議，但他已積極與團隊投入，推動新舊計畫向前。

Turning to the first-quarter results. We were impacted by the seasonal headwinds many companies experienced, namely insurance turnover and reverifications as well as more severe weather, which affected patient access. This impacted both new patient starts and refills.

接著看第一季結果。我們受到許多公司都經歷的季節性逆風影響，主要包括保險更替與重新驗證，以及較為嚴峻的天候，進而影響病患可近性。這同時影響了新病患起始用藥與續配。

On closer examination, we also observed a specific dynamic where some patients prescribed the therapy by early adopters were much further along in their disease and treatment journey than we would have anticipated and therefore, discontinued the treatment earlier than expected. This is not surprising as in many cases, these patients likely had no other alternative therapeutic options with proven clinical benefit. Since January, we've seen a rebound with a strong number of new patients through the end of the first quarter. There also continues to be strong physician conviction with the majority of physicians surveyed at our most recent ATU indicating that the CO-PACK would be their first choice at their patient's next recurrence.

進一步檢視後，我們也觀察到一項特定動態：部分由早期採用者開立此療法的病患，其疾病與治療歷程已遠比我們預期更為後期，因此比預期更早停止治療。這並不令人意外，因為在許多情況下，這些病患可能已沒有其他具已證實臨床效益的替代治療選項。自 1 月以來，我們看到回升，直到第一季末新病患數量表現強勁。醫師信心也持續強勁；在我們最近一次 ATU 調查中，多數受訪醫師表示，當病患下次復發時，CO-PACK 會是他們的第一選擇。

Now on to the numbers. Active prescribers continue to expand and through April, there have been more than 400 unique prescribers to date. And consistent with previous quarters, we continue to see prescriptions split between GynOncs and MedOncs at a 60-40 percentage. Separately, our active patient pool has grown over recent months, indicating patients are staying on therapy longer, but it's too early to provide duration of therapy as it continues to evolve.

接下來看數據。活躍開立處方醫師持續增加，截至 4 月，迄今已有超過 400 位不重複的處方醫師。且與前幾季一致，我們仍看到處方在婦科腫瘤科醫師（GynOncs）與內科腫瘤科醫師（MedOncs）之間以 60/40 的比例分布。另外，我們的活躍病患池在近幾個月有所成長，顯示病患在治療上的持續時間更長，但目前仍過早提供治療持續時間數據，因其仍在演變中。

It's also too early to give an average number of refills, but the trend we are seeing is consistent with what we would expect at this point in the launch. Approximately 65% of commercially eligible patients are using our Verastem Cares Co-Pay Program. The remaining patients did not require co-pay assistance and the average co-pay for commercially insured patients is less than $30. Time to fill initial prescriptions continues to be in the range of 12 to 14 days due to rapid prior authorization approval and our payer mix remains consistent with previous quarters at about half commercial and half Medicare.

目前也仍過早提供平均續配次數，但我們看到的趨勢與此上市階段的合理預期一致。約 65% 符合商業保險資格的病患使用我們的 Verastem Cares 自付額補助（Co-Pay）計畫。其餘病患不需要自付額補助，而商業保險病患的平均自付額低於 30 美元。由於事前授權（prior authorization）核准迅速，首次處方的配藥時間仍維持在 12 至 14 天的區間；我們的付款方組合也與前幾季一致，約一半為商業保險、一半為 Medicare。

As we look ahead and consider our recent learnings, we focused on three key drivers in our business to help patients realize the full benefit of the CO-PACK. The first key driver is to maintain the consistent level of demand of new patient starts. This starts with identifying the right patient for treatment.

展望未來並回顧我們近期的學習，我們聚焦於業務中的三項關鍵驅動因素，以協助患者充分實現 CO-PACK 的全部效益。第一項關鍵驅動因素是維持新患者開始治療的需求量保持一致水準。這始於辨識適合接受治療的正確患者。

Without an ICD-10 code specific to LGSOC, we've identified other proxy measures within EHRs, including mutational status, AI or MEK use that may indicate an appropriate patient for the CO-PACK. Our team is actively working with prescribers when these proxy measures are identified in a patient file. Additionally, we've now added incremental personnel to continue to drive demand and support patient adoption.

由於缺乏針對 LGSOC 的特定 ICD-10 代碼，我們已在電子健康紀錄（EHR）中辨識其他替代性衡量指標，包括突變狀態、AI 或 MEK 的使用情況，這些可能顯示該患者適合使用 CO-PACK。當在患者檔案中辨識到這些替代指標時，我們的團隊正積極與處方醫師合作。此外，我們現已增聘人員，以持續推動需求並支持患者採用。

The second key driver is to drive earlier use at first recurrence. Over the course of the launch, we've observed discontinuations that in part reflect use outside of the attended approved patient population and in LGSOC patients who are much sicker than the patient population in RAMP-201 that was the basis for FDA approval. In fact, in some cases, patients were heading into hospice.

第二項關鍵驅動因素是推動在首次復發時更早使用。在上市推進過程中，我們觀察到的停藥情況，部分反映了在核准適應症所涵蓋的目標患者族群之外使用，以及在病情遠較 RAMP-201（作為 FDA 核准依據）試驗族群更為嚴重的 LGSOC 患者中使用。事實上，在某些情況下，患者已進入安寧照護。

As multiple physicians have noted, disease progression and complications can make it harder for patients to tolerate and absorb oral therapies, underscoring the importance of using the CO-PACK early at first or next recurrence when patients have the best opportunity to realize its full benefits. Our recently launched Reimagine Recurrent LGSOC direct-to-physician and patient campaign is focused squarely on this shift.

如多位醫師所指出，疾病進展與併發症會使患者更難耐受並吸收口服治療，凸顯在首次或下一次復發時及早使用 CO-PACK 的重要性，因為此時患者最有機會充分獲得其全部效益。我們近期推出的「Reimagine Recurrent LGSOC」面向醫師與患者的直達式宣導活動，正是聚焦於推動這一轉變。

The third key driver is to help patients stay on therapy. Recent long-term data from the RAMP-201 trial presented at the Society of Gynecologic Oncology showed that after two years of follow-up, patients on the CO-PACK achieved durable benefit with discontinuation rates consistent with the package insert, findings that physicians view as clinically meaningful.

第三項關鍵驅動因素是協助患者持續接受治療。在婦科腫瘤學會（Society of Gynecologic Oncology）上發表的 RAMP-201 試驗近期長期數據顯示，追蹤兩年後，使用 CO-PACK 的患者獲得持久的療效，且停藥率與仿單一致；醫師認為這些發現具有臨床意義。

Our recent exposure response analysis also demonstrated that early side effects can be effectively managed with dose interruptions after which patients resume at the approved dose and schedule. Setting expectations with both patients and physicians around the AE profile and how to manage through it is a key initiative for the remainder of 2026.

我們近期的暴露—反應分析亦顯示，早期副作用可透過暫停給藥有效管理，之後患者可按核准劑量與給藥時程恢復用藥。就不良事件（AE）特徵以及如何加以管理，對患者與醫師進行預期設定，是 2026 年剩餘期間的一項關鍵工作。

We continue to see a substantial market opportunity for the CO-PACK with growth potential coming from multiple directions, expanding reach among prescribers who ever prescribed the CO-PACK, deepening experience among current prescribers by identifying additional patients in their practices and shifting entrenched prescriber behaviors to starting CO-PACK on their first occurrence when appropriate.

我們持續看好 CO-PACK 的可觀市場機會，其成長潛力來自多個方向：擴大觸及曾經開立過 CO-PACK 的處方醫師、透過在現有處方醫師的診療中辨識更多患者以深化其使用經驗，以及在適當情況下，改變既有的處方行為，使其在首次復發時即開始使用 CO-PACK。

LGSOC is a relatively slow growing but unrelenting cancer where patients stay on their first treatment for several years. Therefore, achieving peak share at first occurrence will take time. But we believe the earlier use of the CO-PACK drives deeper adoption, produces real-world outcomes that mirror our trial experience and establishes the CO-PACK as the new standard of care at first reoccurrence. We remain focused on our core product launch priorities and sustaining steady growth throughout the year.

LGSOC 是一種生長相對緩慢但持續不懈的癌症，患者通常會在第一線治療上維持數年。因此，在首次復發時達到峰值市占需要時間。但我們相信，更早使用 CO-PACK 能推動更深度的採用，產生與我們臨床試驗經驗相呼應的真實世界結果，並使 CO-PACK 成為首次復發時的新照護標準。我們仍專注於核心產品上市優先事項，並在全年維持穩健成長。

I'll now turn the call over to Michael.

接下來我把電話會議交給 Michael。

Thank you, Dan. We continue to make good progress across our pipeline programs, and I'll spend the next several minutes with an overview of our VS-7375 oral KRAS G12D inhibitor program. As Dan mentioned, we've named our VS-7375 trials Target-D. Target-D 101 is our ongoing Phase 1/2 dose escalation, dose expansion and combination evaluation trial. In the dose escalation portion, we are now evaluating the 1,200-milligram daily dose to fully characterize the dose range available.

謝謝你，Dan。我們在各項研發管線計畫上持續取得良好進展，接下來幾分鐘我將概述我們的 VS-7375 口服 KRAS G12D 抑制劑計畫。如 Dan 所提到，我們已將 VS-7375 的試驗命名為 Target-D。Target-D 101 是我們正在進行的第 1/2 期劑量遞增、劑量擴展與聯合治療評估試驗。在劑量遞增部分，我們目前正在評估每日 1,200 毫克劑量，以完整刻畫可用的劑量範圍。

We will complete enrollment across the various expansion cohorts shortly as well as the current cohorts evaluating combinations with chemotherapies. And importantly, we are moving to enroll patients into each of our Phase 2 trials, which I'll describe in more detail. As we mentioned last quarter, the FDA requested that we develop separate Phase 2 protocols for any trials where we are seeking marketing authorization. Thus, we have developed three Phase 2 registration-directed trials in pancreatic cancer or PDAC, non-small cell lung cancer, or NSCLC, and colorectal cancer or CRC. I'll now provide some detail on each of these.

我們也將在短期內完成各個擴展隊列以及目前評估與化療聯合用藥之隊列的收案。更重要的是，我們正著手將患者納入各項第 2 期試驗，我稍後會更詳細說明。如我們上季所提，FDA 要求我們針對任何尋求上市許可的試驗，制定獨立的第 2 期試驗方案。因此，我們已在胰臟癌（PDAC）、非小細胞肺癌（NSCLC）以及大腸直腸癌（CRC）中，制定了三項以註冊為導向的第 2 期試驗。接下來我將逐一提供這些試驗的細節。

Target-D 201 is our second-line PDAC study. This Phase 2 open-label study is designed to evaluate VS-7375 at the 900-milligram daily dose, both as monotherapy and in combination with cetuximab. Based on strong preclinical rationale showing EGFR pathway activation in pancreatic cancer and its role as a potential resistance mechanism to RAS inhibition, we are studying the combination of VS-7375 and anti-EGFR antibodies to potentially deepen and prolong responses.

Target-D 201 是我們的二線 PDAC 研究。這項第 2 期開放標籤研究旨在評估 VS-7375 每日 900 毫克劑量，包含單藥治療以及與 cetuximab 聯合治療。基於強而有力的臨床前理據，顯示 EGFR 路徑在胰臟癌中被活化，且可能作為 RAS 抑制的抗藥機制之一，我們正在研究 VS-7375 與抗 EGFR 抗體的聯合治療，以期加深並延長反應。

We're also taking the opportunity to evaluate VS-7375 and anti-EGFR antibodies in first-line pancreatic cancer where we believe we can generate compelling data. It is worth noting that because VS-7375 has not been associated with skin rash to date, combination with EGFR inhibitors is expected to be clinically feasible and growing tolerability data to date support this.

我們也把握機會在一線胰臟癌中評估 VS-7375 與抗 EGFR 抗體的聯合治療，我們相信可產生具說服力的數據。值得注意的是，由於迄今 VS-7375 尚未與皮疹相關聯，因此與 EGFR 抑制劑聯合使用預期在臨床上可行，而目前累積的耐受性數據亦支持此點。

In addition, we are currently studying the combination of VS-7375 and gemcitabine nab-paclitaxel or GNP in patients with PDAC looking towards a frontline treatment regimen. Target-D 202 is our advanced non-small cell lung cancer study. This Phase 2 open-label study is designed to evaluate VS-7375 at the 900-milligram daily dose in patients who have received one or two prior lines of therapy, including a platinum-based chemotherapy and a PD-1 or PD-L1 blocker.

此外，我們目前也在 PDAC 患者中研究 VS-7375 與吉西他濱合併白蛋白結合型紫杉醇（gemcitabine nab-paclitaxel，GNP）的聯合治療，著眼於一線治療方案。Target-D 202 是我們的晚期非小細胞肺癌研究。這項第 2 期開放標籤研究旨在評估 VS-7375 每日 900 毫克劑量，用於已接受過一至兩線既往治療的患者，既往治療包含含鉑化療以及 PD-1 或 PD-L1 抑制劑。

We are currently evaluating VS-7375 at 600 milligrams daily in non-small cell lung cancer in our 101 trial, and this will provide information at this lower dose. But as in PDAC, we anticipate that the 900-milligram daily dose will be our go-forward monotherapy dose in previously treated non-small cell lung cancer as we look towards potential marketing authorization.

我們目前在 101 試驗中，於非小細胞肺癌評估 VS-7375 每日 600 毫克劑量，這將提供較低劑量下的資訊。但如同在 PDAC 中一樣，展望潛在的上市許可，我們預期每日 900 毫克將是我們在既往治療後非小細胞肺癌中的後續單藥推進劑量。

We are also evaluating VS-7375 monotherapy in patients with non-small cell lung cancer and asymptomatic brain metastases where there remains a significant unmet medical need and an opportunity to improve outcomes. And as previously noted, we are evaluating the combination of VS-7375 plus pembrolizumab without or with platinum pemetrexed chemotherapy in the 101 study looking towards a frontline treatment regimen.

我們也在具有無症狀腦轉移的非小細胞肺癌患者中評估 VS-7375 單藥治療；此領域仍存在顯著未被滿足的醫療需求，並有改善治療結果的機會。此外，如先前所述，我們在 101 研究中評估 VS-7375 合併 pembrolizumab，並可選擇不合併或合併含鉑 pemetrexed 化療，著眼於一線治療方案。

Lastly, we have our Target-D 203 metastatic colorectal cancer study. This Phase 2 open-label study is designed to evaluate VS-7375 at the 900-milligram daily dose as both monotherapy and in combination with EGFR inhibitors, including cetuximab or panitumumab in patients with previously treated colorectal cancer. While we do not expect to see meaningful responses for VS-7375 as a single agent, this will be critical to showing the contribution of PARs for potential combination therapy regulatory submission.

最後，我們有 Target-D 203 轉移性大腸直腸癌研究。這項第 2 期開放標籤研究旨在評估 VS-7375 每日 900 毫克劑量，包含單藥治療以及與 EGFR 抑制劑（包括 cetuximab 或 panitumumab）聯合治療，用於既往治療過的大腸直腸癌患者。雖然我們不預期 VS-7375 作為單一藥物會出現具意義的反應，但這對於在潛在的聯合治療法規申請中，證明 PARs 的貢獻將至關重要。

We're also going to evaluate VS-7375 in combination with anti-EGFR antibodies and the modified FOLFOX6 regimen in the first-line setting, again, to expand the opportunity and help us improve outcomes in patients with colorectal cancer with the goal to develop a frontline combination regimen. Importantly, across all three Phase 2 trials, the primary endpoint is overall response rate by blinded independent central radiological review or BICR, with BICR determined duration of response or DOR as the key secondary endpoint, supporting potential accelerated approvals in each of these three indications.

我們也將在一線治療情境中，評估 VS-7375 與抗 EGFR 抗體以及改良 FOLFOX6 方案的合併使用，再次擴大機會並協助我們改善結直腸癌患者的治療結果，目標是開發一個一線合併治療方案。重要的是，在所有三項第 2 期試驗中，主要終點為由盲態獨立中央影像學審查（BICR）評估的總反應率，而由 BICR 判定的反應持續時間（DOR）為關鍵次要終點，支持在這三個適應症中各自可能取得加速核准。

The protocols have been sent to clinical trial sites, and we anticipate the first patient in each of these studies to occur mid-year, if not sooner. We continue to enroll patients and evaluate the 1,200-milligram dose, which is the highest practical dose that we can administer to define the upper end of the dosing range. We now have updated PK data that show that the 900-milligram dose delivers serum levels of VS-7375 at or above our target level and provides clear separation from the 600-milligram dose.

試驗方案已送交臨床試驗中心，我們預期各研究的首位受試者將於年中入組，甚至可能更早。我們持續入組患者並評估 1,200 毫克劑量，這是我們可給予的最高可行劑量，用以界定給藥範圍的上限。我們目前已有更新的藥物動力學（PK）數據，顯示 900 毫克劑量可使 VS-7375 的血清濃度達到或高於我們的目標水平，並且與 600 毫克劑量呈現明顯區隔。

While we are seeing good responses at 600 milligrams, these data, along with good tolerability, support our enthusiasm for advancing the 900-milligram dose in our Phase 2 trials. As additional data emerge, we expect to finalize the go-forward dose across tumor types and combination settings. As we shared last quarter, our goal is to generate meaningful data sets in these tumor types, both as single agent as well as in combination with other treatments with the goal of potential accelerated approvals in previously treated cancer as well as developing combination strategies to position our regimens in the frontline setting across all three tumor types.

雖然我們在 600 毫克也看到良好反應，但這些數據加上良好的耐受性，支持我們對在第 2 期試驗中推進 900 毫克劑量的熱忱。隨著更多數據出現，我們預期將最終確定跨腫瘤類型及合併治療情境的後續推進劑量。如同我們在上一季分享的，我們的目標是在這些腫瘤類型中產出具意義的數據集，無論是單藥或與其他治療合併，目標是在既往治療過的癌症中爭取可能的加速核准，同時制定合併策略，以便在三種腫瘤類型的一線治療情境中定位我們的治療方案。

Now let me briefly set expectations for our first half update from the Target-D 101 trial. In terms of patient numbers, the safety data set will include a broad set of patients across Target-D 101. However, the number of patients evaluable for efficacy will still be relatively small. Recall that response evaluations require a minimum of two baseline scans, which are typically six to eight weeks apart and not all responses occur at the first scan. And of course, duration of response requires follow-up for months after the initial response determination.

現在我簡要說明我們對 Target-D 101 試驗上半年更新的預期。就患者人數而言，安全性數據集將涵蓋 Target-D 101 中廣泛的患者群。然而，可用於評估療效的患者數仍將相對較少。請記得，反應評估需要至少兩次基線掃描，通常間隔六到八週，而且並非所有反應都會在第一次掃描時出現。當然，反應持續時間則需要在初次判定反應後再追蹤數月。

We note again that meaningful response duration is typically about six months. As we've discussed previously, we believe that administering the highest well-tolerated dose of VS-7375 will maximize the chances for each patient to have a meaningful antitumor effect. And because the 900-milligram dose has been well tolerated to date in over 20 patients in the US, our results of this dose will require several additional months over what was originally projected for the 600-milligram dose. At this time, we can also add that the 400 and 600-milligram doses of VS-7375 in combination with cetuximab are well tolerated and that we are currently evaluating the 900-milligram dose in this combination.

我們再次指出，具意義的反應持續時間通常約為六個月。如我們先前討論過的，我們相信給予 VS-7375 的最高可耐受劑量，將最大化每位患者獲得具意義抗腫瘤效果的機會。且由於 900 毫克劑量迄今在美國超過 20 名患者中耐受性良好，因此該劑量的結果將比原先針對 600 毫克劑量的預估需要多出數個月。目前我們也可補充，VS-7375 的 400 與 600 毫克劑量與西妥昔單抗（cetuximab）合併使用耐受性良好，而我們正評估此合併中的 900 毫克劑量。

To reiterate, we will only be able to provide a preliminary view on activity overall because we've been able to utilize higher doses in our patients in the United States. That said, we see this first half update as an early checkpoint and believe the data set will be meaningful in terms of demonstrating our progress in enrollment, along with a more mature safety update and more PK data.

重申一次，由於我們得以在美國患者中使用較高劑量，因此我們只能提供整體活性的一個初步觀察。即便如此，我們將這次上半年更新視為一個早期檢核點，並相信該數據集在展示我們入組進展、更成熟的安全性更新以及更多 PK 數據方面將具有意義。

We do plan to include some patient cases across tumor types and combinations in the update. Later this year, we expect to provide a more comprehensive data set, including tumor-specific breakdowns and more mature efficacy data as we enroll in our Phase 2 trials for potential marketing applications.

我們確實計畫在更新中納入跨腫瘤類型與合併治療的一些患者案例。今年稍晚，我們預期提供更全面的數據集，包括按腫瘤類型的細分，以及隨著我們在第 2 期試驗中入組以支持潛在上市申請而取得的更成熟療效數據。

Finally, switching gears for a minute to our avutometinib plus defactinib program. We remain on track to report an update on our RAMP-205 study in first-line PDAC before the end of the second quarter of this year.

最後，讓我們暫時轉換到 avutometinib 加 defactinib 計畫。我們仍按計畫在今年第二季結束前，報告我們在一線 PDAC 的 RAMP-205 研究更新。

Now, I'll turn the call over to Dan Calkins.

現在，我把電話會議交給 Dan Calkins。

Thank you, Michael. Our full financial results were included in our press release, so I'll focus on the highlights here.

謝謝你，Michael。我們的完整財務結果已包含在新聞稿中，因此我將在此聚焦重點摘要。

For the first quarter of 2026, we recorded $18.7 million in net product revenue and $2.8 million in product cost of sales. Cost of sales increased in the first quarter in line with the percent increase in net product revenue for the quarter.

2026 年第一季，我們認列 1,870 萬美元的產品淨營收，以及 280 萬美元的產品銷售成本。第一季銷售成本的增加，與當季產品淨營收的百分比增幅一致。

Research and development expenses were $38.2 million for the first quarter of 2026. R&D expenses continue to be driven by both the ongoing global confirmatory Phase 3 RAMP-301 clinical trial with the CO-PACK and the ongoing VS-7375 Target-D 101 Phase 1/2 clinical trial in the US as well as higher costs associated with clinical supply and drug production activities related to our expanded VS-7375 program.

2026 年第一季研發費用為 3,820 萬美元。研發費用持續由多項因素驅動，包括與 CO-PACK 相關、正在進行的全球確認性第 3 期 RAMP-301 臨床試驗，以及在美國進行中的 VS-7375 Target-D 101 第 1/2 期臨床試驗，另加上與我們擴大 VS-7375 計畫相關的臨床供應與藥品生產活動所帶來的較高成本。

SG&A expenses were $22.3 million for the first quarter of 2026. The expenses were driven by commercial activities and operations, including personnel-related costs to support the ongoing CO-PACK launch. I can reiterate that we expect SG&A expenses to remain roughly the same on a quarterly basis throughout 2026 as we remain disciplined in our expense management, making the right investments at the right time to support the ongoing commercial launch efforts.

2026 年第一季銷售、一般及行政（SG&A）費用為 2,230 萬美元。費用主要由商業活動與營運所驅動，包括支持 CO-PACK 持續上市推廣的人員相關成本。我再次重申，我們預期 2026 年 SG&A 費用將在各季大致維持相近水準；我們將在費用管理上保持紀律，在適當的時間進行適當投資，以支持持續的商業上市推廣工作。

For the first quarter of 2026, non-GAAP adjusted net loss was $42.7 million or $0.43 per share diluted compared to non-GAAP adjusted net loss of $42.9 million or $0.79 per share diluted for the first quarter of 2025. Please see our press release for a full reconciliation of GAAP to non-GAAP measures.

2026 年第一季，非 GAAP 調整後淨損為 4,270 萬美元，或稀釋後每股 0.43 美元；相較之下，2025 年第一季非 GAAP 調整後淨損為 4,290 萬美元，或稀釋後每股 0.79 美元。請參閱我們的新聞稿，以取得 GAAP 與非 GAAP 指標之間的完整調節表。

Moving to the balance sheet. We ended the first quarter with 2026 with cash, cash equivalents and investments of $181.7 million. We believe our current cash, combined with the future revenues from the AVMAPKI FAKZYNJA CO-PACK sales will provide cash runway into the first half of 2027. We remain encouraged by the initial launch and look forward to building on the CO-PACK's growth in 2026.

接著看資產負債表。我們在 2026 年第一季末的現金、約當現金及投資為 1.817 億美元。我們相信目前的現金，加上未來來自 AVMAPKI FAKZYNJA CO-PACK 銷售的收入，將可提供資金跑道延伸至 2027 年上半年。我們對初期上市表現仍感到鼓舞，並期待在 2026 年持續推動 CO-PACK 的成長。

Given our current trajectory, I'm pleased to reiterate that we believe the LGSOC franchise will be self-sustaining in the second half of the year with CO-PACK revenues funding both the commercial operations and our avutometinib plus defactinib clinical trials.

基於我們目前的發展軌跡，我很高興再次重申，我們相信 LGSOC 產品線將在今年下半年達到自給自足，由 CO-PACK 收入同時支應商業營運以及我們的 avutometinib 加 defactinib 臨床試驗。

With that, let me turn the call back over to Dan.

接下來，讓我把電話會議交回給 Dan。

Thanks, Dan.

謝謝你，Dan。

Before we open the call to Q&A, our focus for the remainder of 2026 is very clear, and that's to drive strong execution across our commercial launch, move our three Phase 2 trials expeditiously towards potential registrations, determine appropriate VS-7375 combinations for frontline strategies and maintain disciplined capital management while identifying non-dilutive financial opportunities to deliver for patients and our shareholders. Overall, we believe we're well positioned to deliver on our key milestones this year and continue building a leading oncology franchise in RAS/MAPK-driven cancers.

在我們開放問答之前，我們對 2026 年剩餘時間的重點非常明確：推動商業上市的強力執行、加速推進三項第 2 期試驗以邁向潛在註冊、確定適用於一線策略的 VS-7375 合併方案，並在辨識非稀釋性財務機會的同時維持嚴謹的資本管理，以為患者與股東創造價值。整體而言，我們相信我們已具備良好條件在今年達成關鍵里程碑，並持續在 RAS/MAPK 驅動的癌症領域打造領先的腫瘤產品線。

With that, we'll open up the call for questions. Operator?

那麼，我們現在開放提問。接線員？

(Operator Instructions) Eric Schmidt, Cantor.

(接線員指示) Eric Schmidt，Cantor。

Maybe one on each of the two programs. On 7375, what do you think potential partners need to see from either your Phase 1 or early Phase 2 data sets in order to be very interested in the asset? And then two for Dan in terms of the self-sustainability of the CO-PACK franchise. Can you be a little bit more granular in terms of the revenue that gets you to that sustainability?

也許針對兩個專案各問一題。關於7375，您認為潛在合作夥伴需要從你們的第一期或早期第二期資料集中看到什麼，才會對這個資產非常感興趣？另外兩題給Dan，關於CO-PACK業務的自我永續性。在能達到自我永續方面，能否更細緻地說明需要多少營收？

Sure. Eric, thanks for the question. Just to comment on potential partners, we have had a fair amount of interest. And what typically happens in situations like this, it tends to come down to the competitiveness. I think if there's one party interested, it can go on forever.

當然。Eric，謝謝你的問題。先談潛在合作夥伴，我們確實收到相當多的興趣。而在這類情況下通常會發生的是，最後往往取決於競爭態勢。我想如果只有一方有興趣，事情可能會拖很久。

I do think the fact that we've got significant data out of China that aligns well with the preclinical profile, it's really seeing enough data from the US where we show that we can give it in a tolerable way in a way that can be combined and that we start to recapitulate efficacy that puts us in the ballpark of still being potentially best-in-class. And Michael, I don't know if there's anything more you want to add there, but why don't you comment and then we can have Dan C talk about the expenses second half of the year and kind of what we're talking about being covered.

我確實認為，我們已經有來自中國、且與臨床前特徵高度一致的大量資料；接下來真正關鍵的是看到足夠的美國資料，證明我們能以可耐受的方式給藥、能夠合併用藥，並且開始重現療效，讓我們仍有機會落在「同類最佳」的範圍內。Michael，我不知道你是否還想補充什麼；不如你先評論一下，然後我們再請Dan C談談下半年費用，以及我們所說的哪些部分會被涵蓋。

I think you covered it real well, Dan. We need US data, and we need a lot of detail on the patients and their prior therapy, and we're quite optimistic that we'll be able to deliver on that.

Dan，我覺得你講得很到位。我們需要美國資料，而且需要非常詳細的病人資訊與其既往治療情況；我們相當樂觀能夠做到。

Yes. Eric, this is Dan C. So yes, just in terms of the self-sustaining question, obviously, we haven't given guidance in terms of the revenue for the remainder of the year. But just in terms of the expenses, if you look at SG&A expenses from -- on a quarterly basis from when we were pre-commercial to where we are now, that increase has typically been around $10 million to $15 million per quarter. And then from an R&D perspective, if you look specifically at the A+ related programs, that spend has typically been about $10 million to $15 million per quarter as well.

是的。Eric，我是Dan C。關於自我永續的問題，顯然我們尚未就今年剩餘期間的營收提供指引。但就費用而言，如果你看SG&A費用——以季度來看，從我們商業化前到現在，增加幅度通常約為每季1,000萬到1,500萬美元。而從研發角度來看，若特別聚焦於A+相關專案，該支出通常也約為每季1,000萬到1,500萬美元。

And the majority of that spend is really coming from the RAMP-301 trial, which we announced reached full accrual back in December of 2025. So that's now at full accrual. So I don't expect that, that will increase more likely be coming down. So that would give you a good sense of what it would take to be self-sustaining within that program.

而其中大部分支出其實來自RAMP-301試驗；我們在2025年12月宣布該試驗已完成全數收案。所以目前已是全數收案狀態。因此我不預期那部分支出會再增加，反而更可能會下降。這能讓你對在該專案內要達到自我永續所需的條件有一個不錯的概念。

Michael Schmidt, Guggenheim.

Michael Schmidt，Guggenheim。

I had a couple on 7375. Maybe one for Michael first. You talked about the Phase 1 update in the first half of this year. And maybe if you could just comment a little bit more about how the patients perhaps in the US study compared to the GenFleet Phase 1 study that we saw last year.

我有幾個關於7375的問題。也許先問Michael一題。你提到今年上半年會有第一期更新。能否再多評論一下，美國研究中的病人與我們去年看到的GenFleet第一期研究相比，可能有哪些差異？

And also, you mentioned different follow-up with -- depending on which dose was used. And so how comparable will the US update be perhaps to the GenFleet data from last year?

另外，你提到不同劑量會有不同的追蹤時間。那麼，美國的更新資料與去年GenFleet的資料相比，可比性會如何？

Michael, do you want to take that?

Michael，你要回答這題嗎？

Sure. Yes. Sure, Dan. So PDAC is generally treated the same way across the world. And frankly, these days, lung cancer, I mean, KEYTRUDA may or may not be the immunotherapy, but it's generally treated with a platinum agent, typically carbo and since these are adenocarcinomas of pemetrexed.

當然。是的。當然，Dan。PDAC在全球的治療方式大致相同。坦白說，現在肺癌也是如此；KEYTRUDA可能是也可能不是所用的免疫治療，但一般來說會搭配鉑類藥物，通常是carbo（卡鉑），而且由於這些是腺癌，會合併pemetrexed（培美曲塞）。

And again, colorectal cancer, it's pretty standard, whether they're getting FOLFOX or FOLFIRI and some people are getting FOLFIRINOX, it's all pretty similar. The patients are fairly similar. I think the most important difference and the reason we want to continue to study our drug is because the tolerability in the US has been substantially better than what was reported in China. We are not seeing any significant level at all of liver dysfunction.

同樣地，大腸直腸癌也相當標準化，不論是用FOLFOX或FOLFIRI，有些人用FOLFIRINOX，整體都很類似。病人族群相當相近。我認為最重要的差異、也是我們想持續研究我們藥物的原因，是在美國的耐受性明顯優於中國所報告的情況。我們完全沒有看到任何顯著程度的肝功能異常。

We haven't seen any significant hematologic issues at all. And we continue to see that even with patients now who are on for many months. Some who are on for more than six months. We're just not seeing that. We're also not seeing cumulative toxicities, which is really great for a drug that can be given chronically.

我們也完全沒有看到任何顯著的血液學問題。而且即使是目前已用藥多個月的病人，我們仍持續看到這樣的結果。有些病人已用藥超過六個月。我們就是沒有看到那些問題。我們也沒有看到累積性毒性，這對於可長期給藥的藥物來說非常好。

We have really not seen anything major with this drug to date, and it's -- the numbers are starting to climb. So the 600-milligram dose has been studied for a little bit of a while now, but across a whole bunch of different cancers. It was an open study. We'll have a little bit more specifics on it. But I think the points I made in the call were that it takes a while to get responses here.

截至目前，我們確實沒有在這個藥物上看到任何重大問題，而且——樣本數也開始增加。所以600毫克劑量已研究了一段時間，但涵蓋多種不同癌別。這是一項開放性研究。我們會提供更具體的細節。但我在電話會議中提到的重點是：在這裡要看到反應需要一些時間。

I mean you can't even assess the first response until six to eight weeks after initiation of dosing. And remember, when we open a trial, we don't accrue everybody at the beginning. So this is a staggered accrual, of course, with staggered dosing. We all wish this could happen immediately. But the first scan is six to eight weeks and then a confirmatory scan is another six to eight weeks.

我的意思是，開始給藥後要到6到8週才能評估第一次反應。而且請記得，當我們開啟一項試驗時，不會在一開始就把所有人都收進來。因此收案是分批進行的，當然給藥也會分批錯開。我們都希望能立刻發生，但做不到。第一次掃描在6到8週，接著確認性掃描再過6到8週。

And then if like in PDAC when many of your responses are going to occur in the second scan after the first scan because these are tough tumors and they have a lot of scar tissue. It's going to take a while, and that's okay, and that's very good. We absolutely have responses in the first scans after dosing starts, and we've seen responses at second, and we've seen patients who've done really well, have shrinkage of tumors and cross the important 30% threshold for a PR in scan three or four. I don't want to go into any detail, but we're quite pleased with what we're seeing, and we believe that 900 milligrams will be the go-forward dose. So that won't be -- the 900-milligram details will not come until the second half of the year, as we said.

然後像PDAC這樣，很多反應會出現在第二次掃描而不是第一次掃描，因為這些是很棘手的腫瘤，且有大量疤痕組織。這會需要時間，但沒關係，而且這其實是很好的。我們在開始給藥後的第一次掃描就確實看到反應，也在第二次看到反應；也看到一些表現非常好的病人，腫瘤縮小，並在第三或第四次掃描跨過達到PR所需的重要30%門檻。我不想深入細節，但我們對所見結果相當滿意，並且相信900毫克將會是後續推進的劑量。因此——如我們所說，900毫克的細節要到下半年才會公布。

And we'll be able to give a little bit of data on the 600 milligram. But we would far prefer to give you guys substantial data sets in the 20 to 30 patient range with reasonable durability so that we can make some -- you and we can make some intelligent decisions on how this drug is stacking up against others. All of that said, we remain very, very excited about the potential for this to be a best-in-class agent. And I would lastly point out that this drug does not carry rash with it at all nor does it carry stomatitis. And these are really important considerations for patients who could spend a year or more on these drugs.

我們將能提供一些600毫克的資料。但我們更希望能給各位的是更具規模的資料集，大約20到30位病人，且具有合理的持續性，這樣你們以及我們才能就這個藥物與其他藥物的相對表現做出一些——做出更明智的判斷。總而言之，我們仍然對它成為同類最佳藥物的潛力感到非常、非常興奮。最後我還要指出，這個藥物完全不會帶來皮疹，也不會引起口腔炎。對於可能需要使用這類藥物一年或更久的病人而言，這些都是非常重要的考量。

Okay. Understood. And maybe a question on your Phase 2 program. Specifically the 201 study on Slide 12 is schematic and just wanted to ask, so you have Part A and Part B. And I'm just curious what the decision process is for either selecting one of the two cohorts, monotherapy or combination and then whether the Part A and B patients will be pooled at the respectively selected cohort.

好的。了解。另外可能想問一下你們的第二期（Phase 2）計畫。具體來說，第12張投影片上的201研究是示意圖，我只是想確認一下：你們有A部分和B部分。我很好奇在選擇兩個隊列之一（單藥或聯合治療）時的決策流程是什麼？以及A、B兩部分的病人是否會在各自被選定的隊列中合併（pool）分析。

Will this be a 100-patient type -- actually 80 patient type registration cohort? Or how should we think about the decision path as you have sort of multiple steps in these Phase 2 studies?

這會是一個100名病人的——其實是80名病人的——註冊性隊列嗎？或者，考量到你們這些第二期研究似乎有多個步驟，我們應該如何理解你們的決策路徑？

Right. Well, beautiful way to put it, and you correctly figured out what we're really doing here, which is to expect that based on what's going on right now at the 900-milligram dose currently in our Phase 1, we do think 900 milligrams will be good as both a monotherapy and in combination. We think both of these cohorts are going to be important. And we do intend to pull Parts A and B. This is sort of a two-step.

對。你表述得非常好，而且你也正確看出我們真正要做的是什麼：基於我們目前在第一期（Phase 1）900毫克劑量所看到的進展，我們確實認為900毫克無論作為單藥或聯合治療都會是好的選擇。我們認為這兩個隊列都會很重要。而且我們確實打算把A、B兩部分合併（pool）。這有點像兩步走。

It's almost sort of a baby and two-step trial, but we're just putting it in here this way so that we can review this in case there's some unexpected findings here, which frankly, would be different from what we're finding already in the 101 study. We don't believe that's going to happen, but this was -- we discussed it with our statisticians, and we thought this was the most appropriate way to do this. It doesn't really affect our time lines at all because we think both cohorts are going to go through, and we'll have both a monotherapy and a combination. I'll just add one more thing, and that is that these are important cohorts, assuming cetuximab can add efficacy, but it also remember, cetuximab brings about an 80% burden of it. It's a different kind of a rash than you see with some of the pan-RAS inhibitors.

這幾乎像是一個「小型、兩步走」的試驗，但我們用這種方式呈現，是為了在出現一些意外發現時可以回頭檢視；坦白說，那將會與我們在101研究中已經看到的結果不同。我們不認為那會發生，但我們——我們和統計學家討論過，認為這是最合適的做法。這其實不會影響我們的時程，因為我們認為兩個隊列都會推進，我們會同時有單藥與聯合治療。我再補充一點：這些隊列很重要，前提是西妥昔單抗（cetuximab）能增加療效；但也要記得，西妥昔單抗大約有80%的負擔（不良反應負擔）。它造成的皮疹類型不同於一些泛RAS抑制劑（pan-RAS inhibitors）所見的皮疹。

The cetuximab rash is so-called acneiform, and it's actually really well controlled with, frankly, standard acne medicines plus steroids. So a lot of the patients will go on prophylactic minocycline or doxycycline, and that can really mitigate these rashes. But it still comes with a rash. And there are patients even with pancreatic cancer who don't want that. So we think both of these options will be important, and we think we can deliver very significant response rates, which will be correlated with durability with this kind of a drug because it doesn't have cumulative toxicities for both of these cohorts, and we'll have two different options for patients.

西妥昔單抗的皮疹是所謂的痤瘡樣（acneiform），而且其實用標準的痤瘡藥物加上類固醇就能控制得很好。因此很多病人會預防性使用米諾環素（minocycline）或多西環素（doxycycline），這能大幅減輕這些皮疹。但它仍然會伴隨皮疹。而且即使是胰臟癌病人，也有人不想承受這個。所以我們認為這兩種選項都很重要；我們也認為我們能帶來非常顯著的反應率，且在這類藥物上，反應率會與持久性（durability）相關，因為對這兩個隊列而言它沒有累積性毒性，我們將為病人提供兩種不同的選擇。

Okay. And then cetuximab is clearly an interesting choice, I think, in PDAC, but any plans to potentially evaluate combination of 7375 with an investigational pan-RAS inhibitor?

好的。另外，西妥昔單抗在PDAC（胰臟導管腺癌）中顯然是個有趣的選擇；那麼你們是否有計畫評估7375與一個研究用的泛RAS抑制劑（pan-RAS inhibitor）的聯合治療？

We're absolutely considering that, and we're in discussions with folks. We have generated and continue to generate some interesting data in that regard. So we're absolutely looking into that. That said, frankly, there's a lot of different pathways that deserve study in now that we seem to have made a dent in pancreatic cancer, and we're considering multiple other options as well.

我們絕對在考慮，而且也正在和一些夥伴討論。我們已經產生、並且仍在持續產生一些在這方面很有意思的數據。所以我們確實在研究這件事。不過坦白說，既然我們似乎已經在胰臟癌上取得一些突破，現在有很多不同的路徑值得研究，我們也在考慮多個其他選項。

Faisal Khurshid, Jefferies.

Faisal Khurshid，Jefferies。

I wanted to ask about the GenFleet partnership. So when you guys did the partnership, I think you had three RAS programs that you were eligible to in-license. And if you look at the GenFleet pipeline, they have the G12D, the G12C and the multi-RAS. Can you confirm if you guys are able to license the multi-RAS and what the considerations around that could be?

我想問一下GenFleet的合作夥伴關係。所以你們當初做這個合作時，我記得你們有三個RAS項目具備引進授權（in-license）的資格。如果看GenFleet的產品線，他們有G12D、G12C以及multi-RAS。你們能否確認在授權上是否可以取得multi-RAS？以及圍繞這件事的考量可能有哪些？

Yes. This is Dan. So those three molecules were not -- well, except for the G12D, which we developed together with them and chose the lead. The other two programs were not officially part of the original collaboration. We continue to have discussions for us to jump into the pan-RAS space right now.

可以。我是Dan。所以那三個分子——嗯，除了G12D之外；G12D是我們與他們共同開發並選定先導化合物（lead）的。另外兩個項目並未正式納入最初的合作範圍。我們仍在持續討論，是否要在此刻切入泛RAS（pan-RAS）領域。

We'd have to be convinced that it was a differentiated molecule and that, frankly, that combining G12D and pan-RAS is actually the preferred path we might want to go down. And we think we have so many other options. We're still considering it, but there are a lot of other options to look at for combination.

我們必須確信那是一個具差異化的分子，而且坦白說，將G12D與pan-RAS聯合是否真的是我們想走的優先路徑。我們認為我們還有很多其他選項。我們仍在考慮，但在聯合治療方面還有許多其他選項值得評估。

Got it. But you do have two more molecules that you can get from GenFleet under the current deal?

了解。但在目前的協議下，你們確實還能從GenFleet再取得另外兩個分子，對嗎？

We do, and we've not disclosed those targets yet.

是的，我們可以，但我們尚未披露那些標的（targets）。

Leonid Timashev, RBC.

Leonid Timashev，RBC。

I wanted to pivot maybe to the commercial side of A+F. Really appreciate the color on sort of how you see the commercial strategy evolving. But I guess I'm curious if you could provide more details on how you'll actually affect those changes. I mean is there a different way the sales force is going to message? Are the promotional materials going to be different? Are the regions going to shift? I guess how do you actually drive towards those goals that you laid out?

我想把話題轉到A+F的商業端。非常感謝你們分享你們如何看待商業策略的演進。但我想更具體了解，你們實際上會如何推動這些改變？我的意思是，銷售團隊的溝通話術會不同嗎？宣傳材料會不同嗎？區域會重新調整嗎？也就是說，你們要如何實際推動你們剛才提出的那些目標？

No, that's a great question. And the short answer is I'll accept the last one. So we did add two additional sales positions, and that was really driven by the fact that two of the regions were just too big. And so we said all along we were going to right-size the launch. We were in the process of doing a deep dive.

不，這是個很好的問題。簡短回答是：我接受你最後那個問題。所以我們確實新增了兩個額外的銷售職位，主要是因為其中兩個區域實在太大了。因此我們一直說要把上市推進（launch）調整到合適規模（right-size）。我們當時正在進行深入檢視（deep dive）。

We're about six months in when we got to the end of the year. We had that seasonal issue, which frankly, impacted refills more than initial scripts, and it was reauthorizations and things like that, that would push things from January into February We actually had some patients we had to put on free drug for a month until things got sorted out. And so when I -- when we talk about the focus for 2026, some of it was just additional training. Some of it is making sure that we're putting the right amount of effort into the visits after the first prescription and not putting all our effort into getting a prescription. And then implemented a number of different steps with information flow between the specialty pharmacy and really our integrated force, which is both the sales team and the med affairs team to make sure that when there's a delay, and we increased the number of calls to patients so that we are in touch with what's going on with the patient.

到年底時我們大概推進了六個月。我們遇到季節性因素，坦白說，它對續方（refills）的影響大於初次處方（initial scripts）；而且是再授權（reauthorizations）之類的事情，會把一些進度從1月推到2月。我們其實有些病人必須先提供一個月的免費用藥，直到事情理順為止。所以當我——當我們談到2026年的重點時，其中一部分只是加強額外訓練。另一部分是確保在第一次開立處方之後的回訪上投入足夠的精力，而不是把所有力氣都放在拿到一張處方上。此外，我們也在專科藥局與我們整合團隊（包含銷售團隊與醫藥事務團隊）之間，導入了多項資訊流動的措施，以確保一旦出現延遲，我們能掌握狀況；同時我們也增加了對病人的致電次數，讓我們能與病人保持聯繫，了解病人端正在發生什麼。

But also a very deliberate link where if there's a dose delay, somebody is calling on the practice, whether it's med affairs or the sales rep to both find out what's going on and then reinforce the messaging that came out of the SGO meeting recently. We had two big events at the SGO meeting, which that and IGCS tend to be our two big meetings of the year. We had the long-term update to RAMP-201, which showed durability and no increase in side effects with cumulative use over a long period of time. But also, we had a poster on the importance of dose intensity. And one of the things that you're able to do in a clinical trial when you're interacting in a very regular basis is make sure you're reinforcing the protocol rules, which is if there's a side effect, you delay the dose and you restart at full dose.

但同時也建立了一個非常刻意的連結：如果出現劑量延遲，就會有人聯絡診所——不論是醫藥事務（Med Affairs）或業務代表——一方面了解發生了什麼事，另一方面也再次強化近期 SGO 會議所傳達的訊息。我們在 SGO 會議上有兩個重大事件；SGO 與 IGCS 往往是我們一年中兩個最重要的會議。我們公布了 RAMP-201 的長期更新，顯示療效具持久性，且長期累積使用並未增加副作用。此外，我們也展示了一張關於劑量強度重要性的海報。而在臨床試驗中，由於互動非常頻繁，你能做到的一件事就是確保不斷強化試驗方案規則：若出現副作用，就延後給藥，之後再以全劑量重新開始。

That works really well with this drug. I think we were finding with MedOncs in particular, who are used to the dynamics for chemotherapy are a little different where you may get a response earlier and side effects are cumulative, where with this treatment, you tend to get early side effects, and they tend to be predictable things and things that the patient knows they're coming can be dealt with and then the response becomes later. And so really reinforcing the messaging and really the sharing of data on how important it is to get the patient through that first three months or so, so they get the benefit of the treatment. And then we talked about the new campaign that we rolled out. That's something that had been in the works for a little over six months.

這在這個藥物上運作得非常好。我認為我們特別在腫瘤內科醫師（MedOncs）身上觀察到：他們習慣化療的動態略有不同——可能較早出現反應，且副作用會累積；但在這個治療上，通常是早期就出現副作用，而且多半是可預期、病人也知道會發生的狀況，因此可以處理，之後反應才會較晚出現。因此，真正要做的是持續強化訊息並分享數據，說明讓病人撐過前約三個月有多重要，這樣他們才能獲得治療效益。接著我們也談到我們推出的新宣傳活動。這項活動已籌備了六個多月。

When you launch with accelerated approval, you're limited in what you can talk about in the early days. And so this was really our next wave of the promotional campaign that had been planned from the beginning and really reinforces the importance of getting on this treatment early. I think there's another dynamic going on is also at SGO, there was an early report of a frontline LGSOC study that compared platinum-containing chemotherapy followed by as part of the same regimen, an AI versus an AI only. And the combination won out. And I think you're going to start seeing patients as standard of care based on the data that just came out that will get the platinum-based chemotherapy followed by AI as frontline therapy.

當你以加速核准（accelerated approval）上市時，初期能談的內容會受到限制。因此，這其實是我們從一開始就規劃好的下一波推廣活動，並且再次強調及早開始此治療的重要性。我認為還有另一個動態：同樣在 SGO 上，有一項前線（frontline）LGSOC 研究的早期報告，比較含鉑化療，並在同一療程中接續使用芳香化酶抑制劑（AI），對比僅使用 AI。結果是合併治療勝出。我想你將開始看到，根據剛公布的數據，病人會以標準治療（standard of care）接受含鉑化療，之後以前線治療接續 AI。

And I think that really sets us up very nicely to be the next therapy that patients get after that.

而我認為這讓我們非常有利地成為病人在那之後會接受的下一個治療選項。

Graig Suvannavejh, Mizuho.

Graig Suvannavejh，Mizuho。

This is Sam on for Graig. Congrats on the quarter. Maybe one on 7375. So how should we be thinking about the cadence in terms of the timing of readouts? Is there a specific program or indication that you see as, I guess, the most likely path for successful registration-enabled readout and data?

我是 Sam，代 Graig 提問。恭喜本季表現。想問一題關於 7375。我們應該如何看待讀出（readout）時點的節奏與時間安排？是否有某個特定計畫或適應症，你們認為最可能成為成功的、可支持註冊（registration-enabled）的讀出與數據路徑？

Sam, thanks for the question. I'll start, and then I'll turn it over to Julissa to give more specifics on what we'll have when. We believe all three of those indications are important for patients and places where our drug, we believe, will work quite well based on preclinical data. So they're all moving forward in parallel. Our goal is to have those Phase 2 studies largely accrued by the end of this year and then move forward as quickly as possible.

Sam，謝謝你的問題。我先回答，接著請 Julissa 補充更具體的時間點與我們何時會有什麼資料。我們相信這三個適應症對病人都很重要，而且根據臨床前數據，我們認為我們的藥物在這些領域都會有相當好的效果。因此它們都在平行推進。我們的目標是在今年年底前，基本完成這些第二期研究的收案，然後盡可能快速往前推進。

Obviously, there's a lot of movement in PDAC. We're going to have to monitor. We are in an enviable position as a company of our size that we have multiple programs in PDAC, and we're going to have to see how both of those develop to make some decisions on how best to prioritize things while staying right on top of what's going on in the competitive space because obviously, there's a lot going on in PDAC. And then for CRC and lung cancer, again, the preclinical data is really exciting. If you look at the GenFleet data in second-line lung cancer, 50 -- or 69% response rate we're seeing unprecedented response rates as a single agent.

顯然，PDAC（胰臟導管腺癌）領域變化很大。我們必須持續觀察。以我們這樣規模的公司而言，我們在 PDAC 有多個計畫，這是相當有利的位置；我們需要看這兩個計畫各自如何發展，才能做出如何最佳排序優先順序的決策，同時也要緊盯競爭態勢，因為 PDAC 的確有很多進展。至於 CRC（大腸直腸癌）與肺癌，臨床前數據同樣非常令人振奮。如果你看 GenFleet 在二線肺癌的數據，我們看到 50——或 69% 的反應率；作為單藥，我們看到前所未見的反應率。

We're starting to see that we can combine nicely with other agents. And so we've got a lot of choices to make around the frontline path in a very short period of time. But while we do that, and we will be doing frontline Phase 3 studies, we will continue to push forward very aggressively on those potential accelerated approval paths.

我們也開始看到它能與其他藥物很好地合併使用。因此在非常短的時間內，我們在前線（frontline）路徑上有很多選擇需要做決策。但在我們做這些事、並且將進行前線第三期研究的同時，我們也會持續非常積極地推進那些可能走加速核准路徑的機會。

I'll just add just with that. Yes. I think just to reiterate what we said on the call about the timing, again, the update in the first half will show progress on enrollment. We'll share some more mature safety profile data since the one that we provided back in March. And we'll provide some patient cases so that you can get a sense of the efficacy that we're seeing.

我再補充一下。是的。我想再次重申我們在電話會議中提到的時間安排：上半年更新將會展示收案進度。我們也會分享比三月提供的資料更成熟的安全性概況數據。並且會提供一些病人案例，讓大家對我們看到的療效有更直觀的感受。

And then in the latter half of the year, again, the goal is more comprehensive data set, double-digit patient numbers across the tumor types, ideally at the go-forward dose, looking both at mono and combo data sets. So we can make some decisions at that point, looking at all of the variables that were just mentioned.

而在下半年，我們的目標同樣是提供更全面的資料集：在各腫瘤類型中都有雙位數的病人數，理想情況下是在後續要推進的劑量（go-forward dose）下，同時觀察單藥與合併治療的資料集。如此一來，我們就能在那個時間點，綜合剛才提到的所有變數來做一些決策。

Yes. In the first half data release, we'll have much -- we'll have more data on PK. And as Michael mentioned during his prepared remarks, this is the first time we've disclosed that in the US, we are seeing better PK at 900 than 600. And that's both AUC, which is kind of, I guess, the standard measure folks would normally use. But because of the residence time or time on target, being about 24 hours, we actually think Cmax matters a lot.

是的。在上半年的資料發布中，我們會有更多藥物動力學（PK）數據。而如 Michael 在事先準備的發言中提到，這是我們首次揭露：在美國，我們看到 900（mg）的 PK 表現優於 600（mg）。這包含 AUC（曲線下面積），也就是一般大家常用的標準衡量指標。但由於停留時間（residence time）或靶點作用時間（time on target）約為 24 小時，我們其實認為 Cmax（最高濃度）也非常重要。

So it can come out of the blood and still be actively blocking the target, and Jon Pachter presented some really elegant work at AACR last meeting recently. And so we think by seeing that PK going up with the dose, we think it just further strengthens the case for pushing that 900-milligram dose, especially since we are seeing that it's tolerable.

因此它可以從血液中移除，但仍能持續有效阻斷靶點；Jon Pachter 最近在上一場 AACR 會議上展示了一些非常精緻的研究工作。因此，我們認為看到 PK 隨劑量上升而提高，會進一步強化我們推進 900 毫克劑量的理由，特別是因為我們也看到其耐受性良好。

Andres Maldonado, H.C. Wainwright.

Andres Maldonado，H.C. Wainwright。

Congrats on the progress. Two for me for 7375. First, so in the non-small cell lung cancer, you're including an asymptomatic untreated brain metastases cohort. So curious there, is the goal mainly to show systemic activity in a difficult subgroup? Or is there potential to -- do you guys think you have enough CNS exposure to support a differentiated intracranial profile that extends beyond that tissue type?

恭喜進展。我有兩題關於 7375。第一，在非小細胞肺癌中，你們納入了一個無症狀、未治療的腦轉移隊列。想請教其目標主要是要在這個困難亞族群中證明全身性（systemic）活性嗎？或者你們是否認為有足夠的中樞神經系統（CNS）暴露量，能支持一個具差異化的顱內（intracranial）療效特徵，並且可延伸到不只這個組織類型？

And then second question, kind of a macro question. So earlier this quarter, we saw a pan-RAS program report a Grade 5 pneumonitis given the historical trends also seen with approved G12C, how should we be thinking about these events through the lens of an on-off G12D or other strategies targeting G12D?

第二題是比較宏觀的問題。本季稍早，我們看到一個 pan-RAS 計畫通報了 5 級（Grade 5）肺炎（pneumonitis）；考量到已核准的 G12C 也有歷史趨勢，你們認為我們應該如何從 on-off 型 G12D 或其他鎖定 G12D 的策略角度來看待這類事件？

Michael, do you want to take those?

Michael，你想回答那些問題嗎？

Sure. So first on the question of the brain mets. The systemic activity of the drug will be in lung cancer generally is being evaluated now at 600 in the ongoing Phase 1, and we will be doing the 900 in the Phase 2, as you see, as you saw from the deck that we had along with the prepared remarks. There is a separate cohort because, obviously, when you're trying to ascertain the value of the drug, systemically, you tend not to pick patients with metastatic brain disease. That said, lung cancer frequently goes to the brain, unlike colorectal and unlike pancreatic cancer.

當然。首先談到腦轉移（brain mets）這個問題。該藥物在肺癌中的全身性活性目前正在進行中的第1期試驗以600的劑量評估，而我們將在第2期試驗中使用900，如同你們從我們隨同事先準備的發言所提供的簡報中看到的。另外有一個獨立的隊列，因為很明顯地，當你試圖判定藥物的全身性價值時，通常不會選擇有腦部轉移性疾病的病人。話雖如此，肺癌相較於大腸直腸癌與胰臟癌，更常轉移到腦部。

And so in lung, it's especially important to try to see if there's substantial brain activity. The drug does penetrate the brain. I believe GenFleet reported that two out of the five patients that they had who had asymptomatic brain mets had systemic responses to the drug. We haven't been able to ascertain exactly how much the brain mets may have shrunk, but the brain mets clearly did not progress because they wouldn't have been responsive if they had. So this cohort of about 25 patients will be treated at 900, which is a higher dose than GenFleet is able to obtain to see if we can control the brain mets.

因此在肺癌中，特別重要的是嘗試看看是否有顯著的腦部活性。該藥物確實能穿透腦部。我相信GenFleet曾報告，他們收治的5位無症狀腦轉移病人中，有2位對該藥物出現全身性反應。我們尚無法精確判定腦轉移灶縮小了多少，但腦轉移灶顯然沒有進展，因為若有進展就不可能出現反應。因此，這個約25位病人的隊列將以900的劑量治療，這比GenFleet能取得的劑量更高，用以觀察我們是否能控制腦轉移。

And you all know about avutometinib and some of the other amazing therapies that also cross the blood-brain barrier and really can help these patients do very well over time by preventing or treating brain mets. So that's a starting point for potential for this drug that may differentiate it from others. And to reemphasize what Dan said, the fact that we're able to deliver such good systemic levels that are very tolerable so far with the 900 gives us a good shot at being able to drive enough of the drug into the brain and do something about this.

各位也都知道avutometinib以及其他一些同樣能穿越血腦屏障、並且確實能幫助這些病人在長期表現得很好的驚人療法，透過預防或治療腦轉移。因此，這是該藥物潛在差異化的一個起點。並再次強調Dan所說的：我們目前能以900達到相當好的全身性暴露量且耐受性非常好，這讓我們有很好的機會把足夠的藥物推進腦部，並在這方面產生作用。

As far as pneumonitis is concerned, we have not seen any cases of pneumonitis that were believed to be caused by the drug. I believe that they -- that we may have a treatment unrelated pneumonitis case in a patient who already received radiation and it was thought to be a radiation associated, but it was grade 1, and it had zero impact at all on anything we've seen.

至於肺炎（pneumonitis），我們尚未看到任何被認為是由該藥物引起的肺炎病例。我相信他們——我們可能有一例與治療無關的肺炎，發生在一位先前接受過放射治療的病人身上，當時認為與放射線相關；但那是第1級，且對我們所觀察到的任何事情都完全沒有影響。

We've certainly not seen any kind of pulmonary symptoms with our drug that give us any pause. That said, we'll be treating a large number of patients with previously treated lung cancer, many of whom have received chest field radiation, many of whom have had one or more infections, all of which predispose you to downstream lung events. We're obviously hopeful we're not going to see that.

我們當然沒有看到任何與我們藥物相關、會讓我們有所顧慮的肺部症狀。話雖如此，我們將治療大量既往接受治療的肺癌病人，其中許多人接受過胸部照射，許多人曾有一次或多次感染，這些都會使你更容易在後續出現肺部事件。我們當然希望不會看到那種情況。

And lastly, we do not believe, based on our tox studies, there's any drug-related risk of pneumonitis, but that remains to be seen, but nothing important so far.

最後，根據我們的毒理研究，我們不認為存在任何與藥物相關的肺炎風險；但仍有待觀察，不過到目前為止沒有任何重要訊號。

And just to amplify Michael's comments about pneumonitis, we do have access to the entire PV database at GenFleet. And when we heard these events with some of the other drugs, we did a deep dive. And so his comments are informed by that work that's been done.

再補充一下Michael關於肺炎的評論，我們可以取得GenFleet完整的PV（藥物安全監測）資料庫。當我們聽到其他一些藥物出現這些事件時，我們做了深入分析。因此，他的評論是基於已完成的這些工作。

Yuan Zhi, B. Riley.

Yuan Zhi，B. Riley。

Maybe one question on the combination of 7375 plus EGFR inhibitors in the PDAC indication. So with this incremental addition of EGFR inhibitor, which normally patients cannot get because of baseline KRAS mutation, what kind of incremental efficacy you guys are looking to justify the addition of this agent considering the safety liability with this EGFR inhibitor?

我想問一個關於在PDAC適應症中，7375加上EGFR抑制劑的聯合治療問題。因此，隨著額外加入EGFR抑制劑——病人通常因為基線KRAS突變而無法使用——考量到EGFR抑制劑的安全性負擔，你們希望看到怎樣的額外療效增量，才能合理化加入這個藥物？

Michael, do you want to take that one?

Michael，你想回答這題嗎？

Sure. There's two components to this. One is the overall response rate, of course. And the second very important one is durability. It is -- we do believe, and we have some early data that could support that hypothesis that we could deliver a higher response rate.

當然。這裡有兩個面向。第一當然是整體反應率（ORR）。第二個非常重要的是反應的持久性。我們確實相信——而且我們有一些早期數據可能支持這個假設——我們可以帶來更高的反應率。

We -- it's too early yet to say whether we would have an increased durability of response. That said, the mechanism of action of cetuximab is to block -- specifically block not only a growth pathway. It's an accessory growth pathway for sure, for RAS-driven cancers. It's not the primary one.

至於反應持久性是否會提高，現在下結論還太早。話雖如此，cetuximab的作用機制是阻斷——特別是阻斷的不僅是一條生長路徑。對於RAS驅動的癌症而言，它確實是一條輔助性的生長路徑。它不是主要路徑。

But when you block RAS in these cancers, including pancreatic and colorectal and probably some of the other gastrointestinal tumors, the EGFR pathway becomes much more important and blockade of that can be helpful, again, upfront, but also to prevent the development of resistance and running growth pathways through the EGFR pathway. So this could have impact on both sides of this. We will know fairly soon what kind of incremental we'll have. I can't give you a real number. I think what we'd like to do is say that if there are probably patients who would benefit from cetuximab from the get-go. We don't know who they are.

但當你在這些癌症中阻斷RAS（包括胰臟癌與大腸直腸癌，可能還有一些其他腸胃道腫瘤）時，EGFR路徑會變得更重要，而阻斷它可能有幫助——不僅在一開始（upfront），也能用來預防抗藥性的產生，避免生長訊號改走EGFR路徑。因此，這可能在兩方面都產生影響。我們很快就會知道能帶來多大的增量效益。我無法給出一個確切數字。我想我們希望能說的是：可能有些病人從一開始就會受益於cetuximab。但我們不知道他們是誰。

And there'll be other patients who might benefit from down the road after, say, 8 or 9 or 12 months on our drug, if they started to develop resistance, one could imagine adding cetuximab. We think that this development plan that we expect could support accelerated approvals could lead to availability of this combination regimen, maybe not upfront in everybody, but certainly as an option for patients if they start to see progression of their tumor as well as for some patients upfront.

另外也會有一些病人，可能在使用我們的藥物8、9或12個月之後，如果開始出現抗藥性，便可以想像再加入cetuximab而受益。我們認為，這個我們預期可支持加速核准的開發計畫，可能使這個聯合療法得以使用——也許不是每個人都在一開始就用，但至少可作為病人一旦看到腫瘤進展時的選項，同時也可供部分病人一開始就使用。

So I think this provides a lot of flexibility. This is not an option for most of the pan-RAS inhibitors because the strong concerns about added rash here. And I think for the 40% of patients who have PDAC that's G12D and the 20% of patients that have colorectal cancer that's G12D that this could be a really important addition either upfront or down the road.

所以我認為這提供了很大的彈性。對多數pan-RAS抑制劑而言，這不是一個選項，因為對於額外皮疹風險有很強的疑慮。而我認為，對於40%帶有G12D的PDAC病人，以及20%帶有G12D的大腸直腸癌病人而言，這可能是一個非常重要的加成，無論是一開始就用或是在後續加入。

Jeet Mukherjee, BTIG.

Jeet Mukherjee，BTIG。

Two for me. You certainly mentioned that 900 mg is looking like a very suitable go-forward dose. But I was just wondering if you could elaborate a bit further on why this hits the sweet spot. It looks like 1,200 mg is certainly still under evaluation. Was there some limiting factor with that dose perhaps?

我有兩個問題。你們確實提到900 mg看起來是非常合適的後續推進劑量。但我想請你們再多說一點，為什麼這個劑量剛好落在甜蜜點（sweet spot）。看起來1,200 mg仍在評估中。那個劑量是否有某些限制因素？

And then the second question was just related to the target studies. I think you've definitely mentioned that these are designed to be supportive of approval. Have you reached some degree of alignment with the agency on what the bar for approval is? It looks like ORR is a primary endpoint across several of the studies. Is there some threshold you need to exceed? Any details there would be helpful.

第二個問題與目標性研究（target studies）有關。我想你們已經明確提到，這些研究的設計是為了支持核准。你們是否已在某種程度上與主管機關就核准門檻達成一致？看起來多項研究都以ORR作為主要終點。是否需要超過某個門檻值？任何相關細節都會很有幫助。

Michael, do you want to take those?

Michael，你想回答那些問題嗎？

Sure. So just to be really -- it's a simple answer for 1,200. The capsules that we have right now -- I'm sorry, the pills that we have right now are 100-milligram pills. Asking patients to take nine of these to give you 900 mg is the upper limit of what they can really handle in one swallow, if you will, or one session, if you will. For the 1,200, we're going to a split session of six and six split by about 30 minutes because we ask people to take it with food and plenty of water and so on to make sure it gets down there and everything.

當然。所以要講得很清楚——對於1,200（毫克）來說答案很簡單。我們目前有的膠囊——抱歉，我是說我們目前的藥錠是100毫克錠。要病人一次吞下九顆來達到900毫克，基本上已經是他們在一次吞嚥（或一次服用時段）所能承受的上限。至於1,200，我們會分兩次服用，每次六顆，間隔大約30分鐘，因為我們會要求大家隨餐並搭配大量飲水等，以確保能順利吞服並讓藥物到位。

So it's just impractical to go much above 1,200 with the current pill size. That said, we are certainly in the midst of constructing larger pills, which we'll update you guys on when we have that to a point where we think it's real. And hopefully, we won't be -- we don't expect to be marketing this as 100-milligram pills. We expect to be marketing it with higher pill sizes so that we don't have to give people that much. So it's pretty simple and straightforward.

所以以目前的藥錠尺寸來說，要再高於1,200其實不太可行。不過，我們確實正在製作更大劑量的藥錠，等進展到我們認為已經成熟可行時，會再向各位更新。而且希望我們未來不會——我們也不預期會以100毫克錠來上市行銷。我們預期會以更高單錠劑量來上市，這樣就不需要讓病人一次吃那麼多顆。所以這點相當簡單明瞭。

Once we have the larger pills, depending on what we see with 1,200, we may consider going higher. But right now, 1,200 is it. As far as FDA's threshold, I mean, we have not had any discussions with them specifically about what this is. But thankfully, and I think the oncology division of the FDA has been superb about this, particularly for molecularly defined subsets of cancers. They have routinely approved drugs as low as 25%.

等我們有了更大劑量的藥錠後，視1,200的結果而定，我們可能會考慮再往更高劑量走。但目前就是1,200。至於FDA的門檻，我的意思是，我們尚未就這件事與他們特別討論過具體標準。但值得慶幸的是，我認為FDA腫瘤科在這方面表現非常出色，特別是針對以分子特徵界定的癌症亞群。他們一向也會核准低至25%的藥物。

Typically, the 25% to 30% ORR range is what's approvable as a single-arm study, provided there is sufficient durability. If you go to ASCO, most experts will tell you they want to see at least six months duration of response. You all keep in mind that, that's six months plus the 1.5 months minimum, it takes to get to a response. So you're talking 7.5 to 8 months at least on the drug, which for these kinds of tumors is pretty impressive, particularly in heavily pretreated patients. I think those are kind of the thresholds you should be thinking about 30% on the ORR number and six months durability, but those are general numbers, and it's always a review issue with the FDA.

一般而言，單臂試驗若有足夠的反應持久性，25%到30%的ORR區間是有機會獲准的。如果你去ASCO，多數專家會告訴你，他們希望看到至少六個月的反應持續時間。各位也要記得，那是六個月再加上達到反應所需的最低1.5個月。所以等於至少要在藥物上治療7.5到8個月；對這類腫瘤而言相當亮眼，尤其是在重度既往治療的病人。我認為你們可以把門檻大致想成：ORR約30%以及六個月的持久性；但這些都是一般性的數字，最終仍取決於FDA的審查。

James Molloy, Alliance Global Partners.

James Molloy，Alliance Global Partners。

This is Matt on for Jim today. Just two from us. In terms of the launch for A&F, the reimbursement for KRAS undefined and KRAS wild type, is that continuing at similar rates from previous quarters?

今天由Matt代替Jim發問。我們這邊兩個問題。就A&F的上市推廣而言，針對KRAS未定義與KRAS野生型的給付/報銷，是否仍以與前幾季相近的比率持續進行？

Yes, we've seen no change.

是的，我們沒有看到任何變化。

Okay. Excellent. And then do you guys have any anecdotes from treating doctors whose patients have been on treatment for over eight or nine months at this point? And if you could share, that would be very helpful.

好的。很好。另外，你們是否有任何來自治療醫師的軼事分享：目前有病人已經治療超過八或九個月？如果可以分享，會非常有幫助。

Sure. I mean it's anecdotal at this point, given the fact we've only been out for just a year now. But there are patients that have done quite well that are both wild-type and mutant. And we also continue to interact with the sites on RAMP-201. And I recently spent some time with a patient that's been -- never achieved a PR with stable disease, but had a really transformational change in her ability to do things.

當然。我的意思是，以目前來說這些都還是軼事，畢竟我們上市也才剛滿一年。但確實有一些病人表現相當不錯，包含野生型與突變型。我們也持續與RAMP-201的試驗中心互動。我最近也花了一些時間與一位病人交流，她雖然從未達到PR、僅維持疾病穩定，但她的生活能力出現了非常具轉變性的改善。

She went from not being able to vacuum or living room to running a 5k and has been on our drug for, I believe, three to almost four years now. And so we do have a lot of anecdotal information, even going back to the FRAME study, we had a number of patients staying on for a long time. So we do think when it's the right patient that we'll recapitulate what we saw in the clinical trial. As you may recall, in RAMP-201, we had patients from anywhere from one prior therapy to 10 prior therapies. And it tends to be less, I think -- of course, the more prior therapies you have, the more challenged the patient has.

她從連吸塵或打掃客廳都做不到，進步到可以跑5公里；而且我相信她使用我們的藥物已經三年到將近四年了。因此我們確實有很多軼事資訊；甚至回到FRAME研究，我們也有不少病人能夠長期持續用藥。所以我們認為，只要是合適的病人，我們就能在真實世界重現臨床試驗中看到的效果。如各位所記得，在RAMP-201中，病人的既往治療從1線到10線都有。而且我認為通常——當然，既往治療越多，病人的狀況就越具挑戰。

But I think the big difference in the real world versus the clinical trial will be performance status. In most clinical trials, you're limited to performance status 01. And obviously, in the commercial setting, you take anybody who wants to come on the drug. And even though we did hear instances of patients going on cycle and coming off and then you can say, well, they probably shouldn't have gone on the therapy. We've also heard anecdotal stories of patients that were pulled out of hospice put on the drug and did well for a number of months and got a number of months with good quality of life they wouldn't otherwise wouldn't have had.

但我認為真實世界與臨床試驗最大的差異會在體能狀態（performance status）。多數臨床試驗會限制在體能狀態0-1。而在商業用藥情境下，只要有人想用藥，你基本上都會收治。即便我們也聽過一些案例：病人用了幾個療程又停藥，然後你會覺得，嗯，他們可能本來就不該開始這個治療。但我們也聽過一些軼事：有病人原本已進入安寧療護，後來被拉出來改用我們的藥，結果表現良好好幾個月，並且多獲得了好幾個月的良好生活品質，否則是不會有的。

And so those are great stories to hear, and we continue to monitor those. And we're very excited about the franchise. I think we've uncovered some things from seasonality, plus you learn as you go through the launch, and I think we've made some course corrections that it may take a couple of months to see the full benefit of. But I will say with confidence, we already are sure that we will see an increase from Q1 to Q2 that was bigger than the Q4 to Q1.

所以聽到這些故事很令人振奮，我們也會持續追蹤。我們對這個產品線/適應症布局非常興奮。我想我們也從季節性等因素中發現了一些事情；而且在上市推進過程中你會邊做邊學，我們也做了一些策略修正，可能需要幾個月才能看到完整效益。但我可以有信心地說，我們已經確定Q1到Q2的成長幅度會大於Q4到Q1。

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

謝謝。今天的電話會議到此結束。感謝各位參與。您現在可以掛線。