Day One Biopharmaceuticals Inc (DAWN) 2025 Q3 法說會逐字稿

Hello ladies and gentlemen and welcome to Day One Biopharmaceuticals third-quarter 2025 financial and operating results conference call. (Operator Instructions) Please be advised that this conference call is being recorded.

各位女士、先生，歡迎參加 Day One Biopharmaceuticals 2025 年第三季財務與營運業績電話會議。（操作員說明）請注意，本次電話會議正在錄音。

I would now like to turn the call over to your host, Joey Perrone, Senior Vice President of Finance and Investor relations. Thank you. You may begin.

現在，我謹將電話交給主持人，財務和投資者關係高級副總裁喬伊·佩羅內。謝謝。你可以開始了。

Thank you. Hello, everyone, and good afternoon. Welcome to Day One's third-quarter financial and operating results conference call. Earlier today, we issued a press release that outlines the topics we plan to discuss today. You can access the press release and the slides to accompany this conference call on the Investors and Media section of our website at www.dayonebio.com. An audio webcast with the corresponding slides is also available on the website.

謝謝。大家好，下午好。歡迎參加 Day One 第三季財務與營運績效電話會議。今天早些時候，我們發布了一份新聞稿，概述了我們今天計劃討論的主題。您可以在我們網站 www.dayonebio.com 的「投資者與媒體」版塊查看新聞稿和本次電話會議的幻燈片。網站上也提供包含相應幻燈片的音訊網路直播。

Before we get started, I'd like to remind everyone that some of the statements that we make on this call and information presented in the slide deck include forward-looking statements as outlined on Slide 2. Actual events and results could differ materially from those expressed or implied by any forward-looking statements. We encourage you to review the various risks, uncertainties and other factors included in our most recent filings with the SEC and any other future filings that we make with the SEC.

在正式開始之前，我想提醒大家，我們在本次電話會議中發表的一些聲明以及幻燈片中提供的一些資訊包含幻燈片 2 中概述的前瞻性聲明。實際事件和結果可能與任何前瞻性聲明中明示或暗示的內容有重大差異。我們建議您查看我們最近向美國證券交易委員會提交的文件以及我們未來向美國證券交易委員會提交的任何其他文件中所包含的各種風險、不確定性和其他因素。

These forward-looking statements are based on our current estimates and various assumptions and reflect management's intentions, beliefs and expectations about future events, strategies, competition, products and product candidates, operating plans and performance. You are cautioned not to place any undue reliance on these forward-looking statements, and except as required by law, Day One disclaims any obligation to update such statements.

這些前瞻性聲明是基於我們目前的估計和各種假設，反映了管理層對未來事件、策略、競爭、產品和候選產品、營運計劃和績效的意圖、信念和預期。請注意，不要過度依賴這些前瞻性陳述，除法律要求外，Day One 不承擔更新此類陳述的任何義務。

Today, I'm joined by Dr. Jeremy Bender, Chief Executive Officer; Lauren Merendino, Chief Commercial Officer; Charles York, Chief Operating and Financial Officer; and Michael Vasconcelles, Head of Research and Development.

今天，與我一同出席的有：執行長 Jeremy Bender 博士；商務長 Lauren Merendino；營運長兼財務長 Charles York；以及研發主管 Michael Vasconcelles。

I will now turn the call over to Jeremy.

現在我將把通話轉給傑里米。

Thank you, Joey. Good afternoon and thank you all for joining us. Q3 was an outstanding quarter for Day One. We accelerated growth across every key dimension of OJEMDA's performance, new patient starts, total prescriptions and net product revenue. Our early launch momentum and execution have led to steady and sustainable gains quarter-over-quarter, reflecting continued performance across the organization and growing confidence in OJEMDA's differentiated profile among the members of the pLGG prescribing community.

謝謝你，喬伊。下午好，感謝各位的到來。第三季對於Day One來說是一個卓越的季度。我們在OJEMDA的各項關鍵績效指標上都實現了加速成長，包括新患者開戶量、處方總量和產品淨收入。我們早期的上市動能和執行力帶來了季度間穩定且可持續的成長，這反映了整個組織的持續表現，以及pLGG處方群體成員對OJEMDA差異化形像日益增長的信心。

In Q3, we delivered $38.5 million in net product revenue, representing a 15% quarter-over-quarter increase, our strongest quarter for both total revenue and sequential growth so far in 2025. This performance reflects not only increased adoption but also significant and durable treatment persistence, which we'll elaborate on further in a moment.

第三季度，我們的淨產品收入達到 3,850 萬美元，季增 15%，是 2025 年迄今總營收和季增最強勁的一個季度。這一表現不僅反映了接受度的提高，也反映了治療的顯著和持久性，我們稍後將對此進行更詳細的闡述。

The two-year FIREFLY-1 data which are now included in the OJEMDA label, continue to demonstrate a manageable safety profile and durable clinical benefit. The two-year analysis demonstrated that growth velocity decreases resulting from OJEMDA treatment are reversible, with nearly all patients demonstrating catch-up growth post treatment. The median duration of response to OJEMDA in this 2-year analysis also increased from 13 to 18 months.

現已納入 OJEMDA 標籤的兩年 FIREFLY-1 數據繼續證明其具有可控的安全性和持久的臨床益處。為期兩年的分析表明，OJEMDA 治療導致的生長速度下降是可逆的，幾乎所有患者在治療後都表現出追趕性生長。在這項為期 2 年的分析中，OJEMDA 的中位反應持續時間也從 13 個月增加到 18 個月。

Three-year FIREFLY-1 data will be presented later this month at an oral presentation at the Society for Neuro-Oncology Annual Meeting, followed by a full manuscript we expect will be published in the first half of next year. With durable demand, expanding physician experience and disciplined execution, OJEMDA is well positioned to build on its strong trajectory.

FIREFLY-1 的三年數據將於本月晚些時候在神經腫瘤學會年會上以口頭報告的形式公佈，隨後我們將發表完整的論文，預計該論文將於明年上半年發表。憑藉持續的需求、不斷增長的醫生經驗和嚴謹的執行力，OJEMDA 已做好充分準備，並繼續保持強勁的發展勢頭。

With the strength we've seen across key performance drivers and improved visibility into year-end, we are raising the low end of our full year revenue guidance to a new range of $145 million to $150 million for 2025. This new guidance underscores our confidence in the trajectory of OJEMDA's launch and the durability of its growth story.

鑑於我們在關鍵績效驅動因素方面所看到的強勁表現以及對年底業績的更清晰的了解，我們將 2025 年全年收入預期下限上調至 1.45 億美元至 1.5 億美元的新區間。這項新指引凸顯了我們對 OJEMDA 啟動軌跡及其成長動能持久性的信心。

Our pipeline also continues to advance. Our partner, Ipsen, anticipates a mid-2026 EMA approval decision, marking a key step toward bringing OJEMDA to patients in Europe. FIREFLY-2, our global Phase III trial remains on track for full enrollment in the first half of 2026, positioning OJEMDA to potentially move into frontline pLGG in the US. And DAY301, our PTK7 directed ADC continues to advance with dose escalation ongoing in the Phase Ia trial.

我們的研發管線也在持續進行中。我們的合作夥伴 Ipsen 預計將在 2026 年年中獲得 EMA 的批准，這將標誌著 OJEMDA 為歐洲患者帶來治療的關鍵一步。FIREFLY-2 是我們的全球 III 期試驗，目前仍按計劃於 2026 年上半年完成全部入組，這將使 OJEMDA 有可能進入美國一線 pLGG 治療領域。DAY301，我們針對 PTK7 的 ADC，在 Ia 期試驗中繼續推進劑量遞增。

Separately, tovorafenib was added to the National Comprehensive Cancer Network adult glioma treatment guidelines as a Category 2A recommended treatment option for patients with recurrent or progressive BRAF altered disease. Altogether, these milestones highlight both depth and momentum across our portfolio and reinforce Day One's value creation trajectory.

此外，托沃拉非尼被添加到美國國家綜合癌症網絡成人膠質瘤治療指南中，作為 2A 類推薦治療方案，用於治療復發性或進展性 BRAF 改變的疾病患者。總而言之，這些里程碑凸顯了我們投資組合的深度和發展勢頭，並鞏固了 Day One 的價值創造軌跡。

As we look to the end of 2025, our priorities are clear. First, drive adoption of OJEMDA as standard of care in second-line pLGG. Second, continue to advance our pipeline. And third, maintain disciplined expense management to keep us firmly on the path to profitability. Our results this quarter strengthen our confidence in Day One's near-term and long-term financial and pipeline performance. The team remains energized by our progress and focused on continuing to deliver meaningful value for patients, providers and shareholders.

展望 2025 年底，我們的工作重點很明確。首先，推動 OJEMDA 作為二線 pLGG 治療的標準療法。第二，繼續推進我們的產品線。第三，要維持嚴格的費用管理，以確保我們始終走在獲利的道路上。本季的業績增強了我們對 Day One 近期和長期財務及業務發展前景的信心。團隊對我們的進展充滿熱情，並專注於繼續為患者、醫療服務提供者和股東創造有意義的價值。

With that, I'll now hand it over to Lauren, who will provide further insight into our commercial performance.

接下來，我將把發言權交給勞倫，她將進一步分析我們的商業表現。

Thanks, Jeremy, and good afternoon, everyone. Q3 was our strongest quarter since launch, with impressive double-digit acceleration across all key parameters of our business. Net product revenue rose 15% to $38.5 million for the quarter. Total prescriptions grew by 18%, with over 1,200 total prescriptions. And new patient starts accelerated by almost 20% quarter-over-quarter. These results underscore the continuing momentum with this brand.

謝謝你，傑里米，大家下午好。第三季度是我們自成立以來表現最好的一個季度，我們業務的所有關鍵指標都實現了令人矚目的兩位數成長。本季淨產品收入成長15%，達到3850萬美元。處方總數增加了 18%，超過 1200 張處方。新患者數量較上季增加近 20%。這些結果凸顯了品牌持續成長的勢頭。

Let's take a closer look at what drove our business this quarter. We've driven double-digit growth quarter-over-quarter for the 5 consecutive quarters since launch. In the first 3 quarters of this year, we delivered over $102 million in net product revenue, reflecting an 89% increase over full year 2024. This is driven by underlying patient demand reflected in our prescription trends, which you can see on the next slide.

讓我們仔細看看本季推動我們業務發展的因素。自推出以來，我們已連續 5 個季度實現了兩位數的環比增長。今年前三個季度，我們的淨產品收入超過 1.02 億美元，比 2024 年全年成長 89%。這是由潛在的患者需求驅動的，這反映在我們的處方趨勢中，您可以在下一張投影片中看到。

Since launch, we have continued to drive an increase in total prescriptions each quarter. In Q3, this accelerated to 18% with over 1,200 total prescriptions and was fueled by three main drivers. First, an acceleration in new patient starts. The release of the two-year follow-up data from FIREFLY-1 meaningfully enhanced physician confidence in OJEMDA's durable efficacy.

自推出以來，我們每季的處方總量都在持續成長。第三季度，這一比例加速上升至 18%，總處方數超過 1200 張，主要得益於三個因素。首先，新患者數量開始加速成長。FIREFLY-1 兩年追蹤資料的發布顯著增強了醫師對 OJEMDA 持久療效的信心。

We have also demonstrated that the large majority of growth velocity delays are reversible following treatment. Physician feedback on the data has been strongly positive, and we believe these data contributed to achieving our highest ever new patient starts this quarter. We've also seen increased adoption in the second-line, confirming the increasing confidence in our brand.

我們也證明，絕大多數生長速度延遲在治療後是可逆的。醫生們對這些數據給予了非常積極的回饋，我們相信這些數據有助於我們在本季度實現有史以來最高的新患者開診量。我們也看到二線市場的採用率提高，證實了消費者對我們品牌的信心不斷增強。

The second important driver is persistency. A high percentage of pLGG patients stay on therapy each month, building our active patient pool over time. The experience of our EAP patients is an important leading indicator here, and we have some learnings on their persistence that I'll share in a moment.

第二個重要驅動因素是堅持不懈。每個月都有很高比例的 pLGG 患者堅持接受治療，隨著時間的推移，我們的活躍患者群體不斷壯大。我們 EAP 患者的體驗是一個重要的先行指標，我們對他們的堅持性有一些經驗，我稍後會分享。

The third driver of our success has been OJEMDA's excellent payer access. About 90% of pLGG patients are receiving payer approval on their first request, enabling rapid initiation post prescription for most patients.

我們成功的第三個驅動因素是 OJEMDA 出色的支付方准入機制。約 90% 的 pLGG 患者在首次申請時即可獲得支付方批准，使大多數患者能夠在處方開立後迅速開始治療。

Let's look a little deeper at some of these dynamics. Over time, as physicians have gained experience with OJEMDA, we've seen increased adoption in the second-line. Second-line adoption grew more than 60% over the past 12 months based on physicians' self-reported prescribing behavior. Additionally, through our engagements, we are hearing more and more physicians reporting that OJEMDA is their treatment of choice in the second-line.

讓我們更深入地了解這些動態。隨著醫生在使用 OJEMDA 的過程中累積了更多經驗，我們看到二線治療方案的採用率有所提高。根據醫生自我報告的處方行為，過去 12 個月中，二線治療藥物的使用率增加了 60% 以上。此外，透過我們的交流，我們聽到越來越多的醫生表示，OJEMDA 是他們二線治​​療的首選藥物。

Here, you can see a couple of quotes from our physicians who attended a recent advisory board. One, stating that OJEMDA is their treatment of choice in the second-line. And the other, stating they recently changed their treatment paradigm to use OJEMDA in the second-line as the first targeted therapy after a patient fails chemotherapy. Though this is encouraging progress, considerable opportunity remains for continued adoption of OJEMDA as it becomes the standard of care in second-line.

在這裡，您可以看到我們幾位參加最近一次顧問委員會會議的醫生的引言。一、聲明 OJEMDA 是他們二線治​​療的首選藥物。另一家公司表示，他們最近改變了治療模式，將 OJEMDA 作為二線治療藥物，作為患者化療失敗後的首選標靶治療。儘管這是一個令人鼓舞的進展，但隨著 OJEMDA 逐漸成為二線治療的標準，其推廣應用仍有相當大的空間。

While the persistency data for our commercial new patient starts is still maturing, our EAP cohort is a helpful leading indicator as you can see on the right-hand side of this slide. These patients are further along in their treatment, offering a longer-term view. US EAP patients had a median duration of treatment of 20 months, which is consistent with what we expected based on our FIREFLY-1 trial results.

雖然我們商業新患者起始治療的持續性數據仍在完善中，但正如您在本投影片右側所看到的，我們的 EAP 隊列是一個有用的領先指標。這些患者的治療進展較為順利，可以提供更長遠的視角。美國 EAP 患者的治療持續時間中位數為 20 個月，這與我們根據 FIREFLY-1 試驗結果所預期的結果一致。

Additionally, we've seen that for those EAP patients who have completed 24 months on OJEMDA, three fourth of them received treatment beyond 24 months. While EAP patients have provided valuable insights, they currently represent a small fraction of our business today. In fact, commercial new patient starts now account for roughly 90% of our active patients at the end of Q3.

此外，我們發現，在接受 OJEMDA 治療 24 個月的 EAP 患者中，有四分之三的人在 24 個月後繼續接受治療。雖然 EAP 患者提供了寶貴的見解，但他們目前只占我們業務的一小部分。事實上，截至第三季末，商業新患者數量約占我們活躍患者的 90%。

Another pillar of our growth has been expanding both breadth and depth of our prescribing base. The graph on this slide demonstrates the increase we've seen in both breadth and depth over time based on commercial new patient starts only, excluding EAP patients. The upper line of the graph represents breadth and shows a continuing growth trajectory in the number of accounts prescribing OJEMDA. While all of our Priority 1 accounts and the large majority of our Priority 2 accounts have already prescribed, we continue to drive breadth by gaining new prescribing accounts in our Priority 3 group.

我們成長的另一個支柱是擴大了處方基礎的廣度和深度。此投影片上的圖表顯示了隨著時間的推移，我們在廣度和深度方面所看到的增長，該增長僅基於商業新患者開始治療的數據，不包括 EAP 患者。圖表的上半部代表廣度，顯示使用 OJEMDA 處方的帳戶數量持續成長。雖然我們所有的一級優先客戶和絕大多數二級優先客戶都已經開立了處方，但我們仍在透過獲得三級優先客戶群中的新處方客戶來擴大業務範圍。

The layers of the graph show depth. Over 60% of prescribing accounts have treated multiple patients with OJEMDA. Notably, the number of accounts treating four or more patients grew 28% quarter-over-quarter, and over 80% of our Priority 1 accounts have now treated four or more patients. You'll also notice that we've added a new layer since last quarter to represent those accounts with nine or more patients. This, combined with the other insights from this graph, continue to show the progress we're making in the depth of prescribing and establishing OJEMDA as a trusted treatment for relapsed/refractory pLGG patients.

圖表的層次結構顯示了深度。超過 60% 的處方帳戶使用 OJEMDA 治療過多名患者。值得注意的是，治療四名或以上患者的帳戶數量環比增長了 28%，超過 80% 的一級優先帳戶現在已治療了四名或以上患者。您還會注意到，自上個季度以來，我們增加了一個新的圖層，用於表示擁有九名或更多患者的帳戶。結合該圖表中的其他見解，這繼續表明我們在處方深度和將 OJEMDA 確立為復發/難治性 pLGG 患者的可靠治療方法方面取得了進展。

We are excited about the substantial opportunity which remains for OJEMDA. Our commercial team continues to focus on two principal levers: driving new patient starts and optimizing persistence. Through disciplined execution against these priorities, we are confident that we will continue to yield double-digit growth over time. I'm incredibly proud of what the commercial team has delivered since launch and especially this quarter. It shows that we execute with excellence across all facets of commercial and continue to deliver for our customers, and most importantly, for pLGG patients.

我們對 OJEMDA 仍然擁有的巨大發展機會感到興奮。我們的商業團隊繼續專注於兩個主要方面：推動新患者註冊和優化患者留存率。透過嚴格執行這些優先事項，我們有信心隨著時間的推移，我們將繼續實現兩位數的成長。我為商業團隊自產品上市以來，特別是本季所取得的成就感到無比自豪。這表明我們在商業的各個方面都表現出色，並繼續為我們的客戶，尤其是 pLGG 患者提供服務。

To better reflect this momentum, we are raising our guidance range to $145 million to $150 million for 2025. Our clinical and medical teams continue to deliver compelling data and analyses that enhance the OJEMDA product profile, providing new insights to physicians on what to expect with OJEMDA. This quarter, the FIREFLY-1 two-year follow-up data was an accelerator for our brand, leading to increases in confidence from prescribers with a meaningful step-up in new patient starts and overall growth for the quarter. This is an important step forward in building our product profile with long-term data.

為了更能反映這一發展勢頭，我們將 2025 年的業績預期範圍上調至 1.45 億美元至 1.5 億美元。我們的臨床和醫療團隊不斷提供令人信服的數據和分析，以增強 OJEMDA 的產品概況，為醫生提供關於 OJEMDA 預期效果的新見解。本季度，FIREFLY-1 兩年追蹤數據加速了我們品牌的發展，提高了處方醫生的信心，顯著提升了新患者的開藥量，並實現了本季度的整體成長。這是利用長期資料建構產品概況的重要步驟。

Later this month, the three-year follow-up data for FIREFLY-1 will be an oral presentation at the Society for Neuro-Oncology Annual Meeting with a peer-reviewed journal publication plan for next year. These data will provide a longer-term view of safety and efficacy with OJEMDA and also highlight patients' journeys after completing their initial course of therapy. Data reporting time to next treatment and treatment-free interval will be important potential differentiators for physicians in the care of their patients.

本月晚些時候，FIREFLY-1 的三年隨訪數據將在神經腫瘤學會年會上進行口頭報告，並計劃於明年在同行評審期刊上發表。這些數據將提供 OJEMDA 的長期安全性和有效性數據，並突顯患者完成初始療程後的治療歷程。數據報告顯示，下次治療時間和無治療間隔時間將成為醫生在照護患者時的重要潛在區分因素。

Through continuing to build OJEMDA's clinical profile and excellence in commercial execution, we are confident that we will establish OJEMDA as the new standard of care in second-line BRAF-altered pLGG.

透過不斷提升 OJEMDA 的臨床療效和卓越的商業執行力，我們有信心將 OJEMDA 確立為 BRAF 突變型 pLGG 二線治療的新標準。

I'll now hand it over to Charles to provide an update on our financial performance.

現在我將把發言權交給查爾斯，讓他報告一下我們的財務表現。

Earlier today, we reported our Q3 2025 financial results. For today's call, I'll highlight a few key takeaways that demonstrate the strong commercial execution and durable growth trajectory of OJEMDA, along with our continued focus on financial discipline and operational excellence. We're very pleased with the progress we've made this year.

今天早些時候，我們公佈了 2025 年第三季財務業績。在今天的電話會議上，我將重點介紹一些關鍵要點，這些要點體現了 OJEMDA 強大的商業執行力和可持續的成長軌跡，以及我們對財務紀律和卓越營運的持續關注。我們對今年的進展感到非常滿意。

Following OJEMDA's April 2024 approval, momentum continues to build, fueled by growing physician confidence and compelling longer-term follow-up data from our FIREFLY-1 study. These results are translating directly into performance, with double-digit growth across revenue, prescriptions and new patient starts this quarter. These are all great indicators for continued momentum ahead.

繼 OJEMDA 於 2024 年 4 月批准後，勢頭持續增強，這得益於醫生信心的增強以及我們 FIREFLY-1 研究提供的令人信服的長期隨訪數據。這些成果直接轉化為業績，本季收入、處方量和新患者數量均實現了兩位數成長。這些都是未來發展動能持續的良好指標。

For Q3, US OJEMDA net product revenue was $38.5 million, which grew 15% compared to the second quarter. Our Q3 results bring our year-to-date net product revenue to $102.6 million. Additionally, revenue from OJEMDA exceeded the combined cost of sales and SG&A for the first time this quarter, highlighting both its growing contribution to the enterprise and the scalability of our operating model.

第三季度，美國 OJEMDA 淨產品收入為 3,850 萬美元，比第二季度成長 15%。第三季業績使我們今年迄今的淨產品收入達到 1.026 億美元。此外，本季 OJEMDA 的營收首次超過了銷售成本和 SG&A 的總和，這凸顯了其對企業日益增長的貢獻以及我們營運模式的可擴展性。

Based on the continued strength of underlying demand and improved visibility into Q4, we are raising our full year 2025 revenue guidance to a new range of $145 million to $150 million. This revised range reflects our confidence in the trajectory of the launch and assumes continued double-digit sequential growth in the fourth quarter.

基於持續強勁的潛在需求和第四季前景的改善，我們將 2025 年全年營收預期上調至 1.45 億美元至 1.5 億美元的新區間。這項修訂後的範圍反映了我們對產品上市前景的信心，並假設第四季將繼續保持兩位數的環比成長。

Turning now to expenses. We continue to manage operating costs effectively with total operating expenses of $59.6 million, which includes $9.6 million of noncash stock-based compensation. This is the second consecutive quarter with declining expenses, approximately 9% compared to Q2. This continued trend reflects our data-driven approach to capital allocation.

接下來談談費用。我們繼續有效控制營運成本，總營運支出為 5,960 萬美元，其中包括 960 萬美元的非現金股票補償。這是連續第二季支出下降，與第二季相比下降了約 9%。這一持續趨勢反映了我們以數據為導向的資本配置方法。

We prioritized investment in the areas with the highest potential return and intentionally scaled back where we don't see a clear path to value creation. That said, we do expect Q4 expenses to increase modestly, reflecting the timing of planned commercial and clinical activities. We believe these are the right investments to support sustained growth in 2026 and beyond.

我們優先投資於最具潛在回報的領域，並有意縮減在那些我們看不到明確價值創造路徑的領域的投資。儘管如此，我們預計第四季度支出將略有增加，這反映了計劃中的商業和臨床活動的開展時間。我們相信這些投資是正確的，能夠支持公司在 2026 年及以後的持續成長。

We also continue to closely manage channel stock levels to align with demand. Historically, we've guided to maintaining approximately two to four weeks of product on hand. In this quarter, we finished at the lower end of the range. This reflects timing of orders and growing demand for OJEMDA rather than any supply constraints, and we'll continue to actively monitor channel stock to ensure unconstrained product availability for our patients.

我們也會繼續密切管理通路庫存水平，以適應市場需求。從歷史上看，我們一直建議保持大約兩到四周的產品庫存。本季度，我們的業績處於預期範圍的下限。這反映的是訂單的時機和對 OJEMDA 日益增長的需求，而不是任何供應限制，我們將繼續積極監控通路庫存，以確保我們的患者能夠不受限制地獲得產品。

On gross to net, we continue to guide to a range of 12% to 15% for the year. Due to the price increase we implemented in July, we're at the high end of that range for this quarter, which reflects short-term increases in Medicaid rebates that occur after a price change. We ended the quarter with $451.6 million in cash and no debt, reflecting only a slight decrease from the prior quarter as we continue to invest in advancing our commercial and pipeline priorities.

就毛利與淨利潤的比率而言，我們繼續預期全年成長率在 12% 至 15% 之間。由於我們在 7 月實施了漲價，本季我們處於該區間的高端，這反映了價格變化後醫療補助回扣的短期增長。本季末，我們擁有 4.516 億美元的現金，且無任何債務，與上一季相比僅略有下降，因為我們將繼續投資推進我們的商業和研發管線重點項目。

With strong revenue growth translating into higher cash flows and expenses holding relatively steady, we are seeing continued improvement in quarterly net cash burn. While we are not guiding to profitability, maintaining financial discipline and advancing long-term value creation remain top priorities for the organization.

由於強勁的收入成長轉化為更高的現金流，而支出保持相對穩定，我們看到季度淨現金消耗持續改善。雖然我們並未追求獲利，但保持財務紀律和推進長期價值創造仍然是本組織的首要任務。

Finally, business development remains a key strategic priority for future growth. We continue to actively evaluate opportunities that complement our commercial capabilities and our long-term strategy. Our approach remains focused on identifying assets where we can create meaningful value through development or commercialization expertise.

最後，業務發展仍是未來成長的關鍵策略重點。我們將繼續積極評估能夠補充我們商業能力和長期策略的機會。我們的方法仍然專注於尋找能夠透過開發或商業化專業知識創造有意義價值的資產。

Overall, Q3 represents another strong step forward, both commercially and operationally with accelerating demand, expanding prescriber depth and important upcoming data disclosures, we believe the foundation we've built positions us well for advancing our long-term objectives.

總體而言，第三季在商業和營運方面都代表著又向前邁出了堅實的一步，隨著需求的加速增長、處方醫生數量的增加以及即將公佈的重要數據，我們相信我們所建立的基礎將使我們為推進長期目標做好充分準備。

I'll now hand it back to the operator for Q&A.

現在我將把電話交還給接線員進行問答。

Thank you. At this time, we'll be conducting a question-and-answer session. (Operator Instructions)

謝謝。屆時我們將進行問答環節。（操作說明）

Tara Bancroft with TD Cowan. Please proceed with your question.

塔拉·班克羅夫特與TD·考恩。請繼續提問。

So I guess I'm curious to what extent you could possibly describe even qualitatively what impact you're seeing on both the rate of discontinuations and duration of therapy, especially in non-EAP patients now that physicians have had a good amount of exposure this year to various data sets.

所以我很好奇，您能否定性地描述一下，您觀察到的停藥率和治療持續時間受到的影響，尤其是在非 EAP 患者中，因為今年醫生們已經接觸到了相當多的各種數據集。

I know previously, you had mentioned that some proportion of discontinuations were driven by off-label use in settings with lower duration and also improper treatment of rash. So just curious to get an update here considering that you saw a really great level of increased demand this quarter that was driven mostly by that data.

我知道您之前提到過，部分停藥是由於在療程較短的情況下進行超適應症用藥以及皮疹治療不當造成的。鑑於本季需求大幅成長，而這主要也是由這些數據驅動的，所以我很好奇這方面的最新情況。

Hi Tara, thanks for the question. This is Jeremy. So first off, it was a great quarter. I think you captured it appropriately. And that was really on both the new patient start dimension, but also the persistence as noted. So let me ask Lauren to comment on the sort of non-EAP commercial use group.

嗨，塔拉，謝謝你的提問。這是傑里米。首先，這個季度業績很棒。我覺得你描述得很到位。如同前面所提到的，這確實體現在新患者的治療啟動方面，以及治療的持續性方面。那麼，請 Lauren 對非 EAP 商業用途群體發表一下看法。

Yes. Thanks, Tara, for the question. At this point, the data is still maturing on our commercial patients. So what I can say is it's consistent with our expectations. But I really can't give any details beyond that. But I do think that the median duration of therapy in the EAP patients of 20 months is significant and is a leading indicator for us. That data is not final. There still are a number of patients who remain on therapy who have not yet reached the point of receiving OJEMDA for 24 months yet. So that number may evolve. But the median will likely stay the same, but the additional duration beyond 24 months is an evolving data point.

是的。謝謝塔拉的提問。目前，我們商業患者的數據仍在不斷改進中。所以可以說，這符合我們的預期。但我真的不能透露更多細節了。但我認為 EAP 患者的治療持續時間中位數為 20 個月，這具有重要意義，並且是我們的一個重要指標。該數據並非最終版本。還有一些患者仍在接受治療，但尚未達到接受 OJEMDA 治療 24 個月的階段。所以這個數字可能會改變。但中位數可能會保持不變，但超過 24 個月的額外持續時間是一個不斷變化的數據點。

Yes. And Tara, I would really emphasize that latter point because it's very much what we expected and hoped we would see for patients, and that is that for those patients that have tumors where small changes in the growth can impact function, it makes sense to keep them on therapy. And we're seeing that in the real world through the EAP program to date. For the non-EAP commercial group, it's really just too early to say at this stage.

是的。塔拉，我真的要強調後一點，因為這正是我們期望和希望看到的，那就是對於那些腫瘤生長微小變化就會影響功能的患者來說，讓他們繼續接受治療是有意義的。到目前為止，我們已經透過員工協助方案 (EAP) 在現實世界中看到了這一點。對於非 EAP 商業集團而言，現在下結論還為時過早。

Okay, that makes so much sense. Very helpful. Thanks so much.

哦，這很有道理。很有幫助。非常感謝。

Thank you.

謝謝。

Anupam Rama, JP Morgan.

Anupam Rama，摩根大通。

Hey guys, thanks so much for taking the question. I just wanted to focus a little bit on the 3-year data for pivotal FIREFLY-1 study that's coming out at SNO later this month. Can you just expand a little bit more on what you're looking for in that data that could inform how we think about treatment duration or other commercial levers for OJEMDA moving forward? Thanks so much.

各位，非常感謝你們回答這個問題。我只想重點介紹一下本月稍後在SNO會議上公佈的關鍵性FIREFLY-1研究的3年數據。您能否再詳細說明一下，您希望從這些數據中發現什麼，以便我們思考治療持續時間或 OJEMDA 未來其他商業槓桿？非常感謝。

Thanks for the question, Anupam. Mike will answer that one for you. Mike?

謝謝你的提問，Anupam。麥克會為你解答這個問題。麥克風？

Thanks, Jeremy. Anupam, Mike Vasconcelles here. Yes, we're really excited about these data coming up at SNO. I think given the nature of the disease, the long-term follow-up data in our clinical development program is going to be important for a variety of reasons for the foreseeable future. So of course, in addition to update on safety and duration of response, I think what's going to be important to keep an eye out for are the time-to-event analysis that will be shared specifically around the time to next treatment and a treatment-free interval as well as progression.

謝謝你，傑瑞米。我是 Anupam，我是 Mike Vasconcelles。是的，我們對SNO即將公佈的這些數據感到非常興奮。我認為，鑑於這種疾病的性質，在可預見的未來，我們臨床開發計畫中的長期追蹤數據對於各種原因都將非常重要。當然，除了安全性和反應持續時間的更新之外，我認為需要密切關注的是事件發生時間分析，特別是關於下次治療時間、無治療間隔以及病情進展情況的分析。

The reason that's important is because it will be important in second and subsequent lines of therapy to really understand that in the context of other available therapies where we know there may be some biologic sort of events that occur when patients come off therapy that we want to see if are going to be distinguishable for OJEMDA. I think we'll also get a sense of perhaps early retreatment information that could be meaningful for clinicians and patients.

之所以重要，是因為在第二線及後續治療中，真正理解這一點至關重要，尤其是在與其他可用療法進行比較時。我們知道，當患者停止治療時，可能會發生一些生物學事件，我們想看看這些事件是否能透過 OJEMDA 區分。我認為我們或許還能獲得一些早期再治療訊息，這對臨床醫生和患者來說可能很有意義。

Thanks. And what I would focus on within the category of events that happen off treatment for other therapies is really that there is, to kind of add to Mike's answer, some rebound growth that physicians observe with use of MEK inhibitors in particular, when patients come off therapy. That's rebound tumor growth. So we'll be looking at that as part of the 3-year analysis as well as those time to event points that Mike mentioned.

謝謝。而我想重點關注的是，在其他療法停止治療後發生的事件中，正如 Mike 的回答所補充的，醫生們觀察到，特別是當患者停止使用 MEK 抑制劑時，會出現一些反彈增長。這是腫瘤反彈生長。因此，我們將把這一點以及麥克提到的那些事件發生時間點納入三年分析中。

Thanks so much for taking the question.

非常感謝您回答這個問題。

Andrea Newkirk with Goldman Sachs. Please proceed with your question.

安德里亞·紐柯克，高盛集團。請繼續提問。

Hi, this is Morgan on for Andrea Newkirk. Thank you for taking our question. Can you speak how the addition of the FIREFLY data to the label has impacted rates of off-label MEK inhibitor usage? And then on the payer side, you noted 90% plus rates of coverage approval on first submission. Is there a reason to think that favorable coverage could impact the rates of off-label MEK inhibitor usage as well? Thank you.

大家好，我是摩根，代安德里亞紐柯克為您報道。感謝您回答我們的問題。您能否談談將 FIREFLY 數據添加到標籤中對 MEK 抑制劑的超適應症使用率產生了哪些影響？而在付款方方面，您注意到首次提交申請後，承保批准率超過 90%。是否有理由認為有利的健保覆蓋範圍也會影響MEK抑制劑的非適應症使用率？謝謝。

So let me -- I'm going to ask Lauren to answer the second portion of your question. On the first, I want to clarify and make sure I understand. Was your question related to the NCCN listing that we received for OJEMDA in adult gliomas, and off-label uses?

那麼，讓我——我將請勞倫來回答你問題的第二部分。首先，我想澄清一下，確保我理解正確。您的問題是否與我們收到的 OJEMDA 在成人膠質瘤中的 NCCN 清單以及超適應症用藥有關？

Yes.

是的。

Okay. Yes, I'd say, first off, we weren't aware that, that was a listing that was going to occur. And of course, we're interested. We think there's potential utility there based on data that we've seen in the past for OJEMDA. It's a little early to say whether or not it will have any material impact on off-label use, but it certainly could, given that in particular, in adult settings, those NCCN listings can be influential as far as physicians electing to try treatments that are not necessarily approved for a specific tumor. So I think it's a stay tuned story.

好的。是的，首先，我們事先並不知道會有這樣的掛牌出售。當然，我們很有興趣。根據我們過去從 OJEMDA 獲得的數據，我們認為這方面具有潛在的實用價值。現在斷言它是否會對標籤外使用產生任何實質影響還為時過早，但肯定會有影響，因為尤其是在成人領域，NCCN 的這些清單可能會影響醫生選擇嘗試那些不一定被批准用於特定腫瘤的治療方法。所以我覺得這將會是一個值得期待的故事。

And Lauren can comment on your question around reimbursement.

勞倫可以就您提出的報銷問題發表意見。

Yes. So just remember that NCCN is an independent organization. And so although they've made their recommendation, that is not reflected in our label in any way. And so the commercial team must remain strictly within our label. So we have no ability to engage with physicians on that topic at all. But I will say that payers do sometimes leverage NCCN guidelines to inform their policies. But again, this is nothing that we can participate in, and that would be completely up to those payers.

是的。所以請記住，NCCN是一個獨立的組織。因此，儘管他們提出了建議，但這並沒有以任何方式反映在我們的標籤上。因此，商業團隊必須嚴格遵守我們的品牌規則。因此，我們完全沒有辦法就此話題與醫師進行交流。但我必須指出，支付方有時確實會利用 NCCN 指南來制定政策。但再次強調，這並非我們能夠參與的事情，完全取決於那些付款方。

Yes. And I would add that our rates of reimbursement for both on-label and off-label have been so high already that I'm not sure that reimbursement has been a barrier to use. So it's probably more likely to be a circumstance where that recommendation itself could lead to use based on physician decision-making that's really outside of our control.

是的。我還要補充一點，我們對藥品說明書內使用和說明書外使用的報銷率已經非常高了，所以我不確定報銷是否是使用藥品的障礙。因此，更有可能的情況是，該建議本身可能會導致醫生根據我們無法控制的決策來決定是否使用該藥物。

Okay, that's helpful. Thank you.

好的，這很有幫助。謝謝。

Thank you, Morgan.

謝謝你，摩根。

Alex Stranahan, Bank of America.

Alex Stranahan，美國銀行。

Hey guys, thanks for taking our questions and congrats on the strong quarter. Two from us. Curious if you saw any gross to net changes in 3Q? Just trying to pair the different growth rates that you mentioned, both on revenues and scripts.

各位，謝謝你們回答我們的問題，也恭喜你們本季業績優異。我們兩人都同意。想問您第三季毛利和淨利有沒有變化？我只是想把您提到的不同增長率進行匹配，包括收入和劇本的增長率。

And then second, on DAY301, I guess how has enrollment been going? Is it sort of proceeding as you would have expected? And any updated thoughts on PTK7 as a target given the shifting development landscape for ADCs against the target? Thank you.

其次，在第 301 天，我想問招生狀況如何？事情的進展是否基本上符合你的預期？鑑於針對PTK7標靶的抗體藥物偶聯物（ADC）研發格局的變化，您對PTK7作為標靶有何最新看法？謝謝。

Alec, thanks for the question and comment. Let me ask Charles to comment on gross to nets and then Mike regarding 301 and PTK7.

Alec，謝謝你的提問和評論。我請查爾斯評論一下總桿數和淨桿數，然後請麥克評論一下 301 和 PTK7。

Alec, this is Charles. So on the gross to net, you should hear from us that we were definitely at the high end of our 12% to 15% range that we've guided on. That's consistent with what we expected going into the quarter. As you recall from previous conversations, we did take a price increase as of July 1, and the result of that is CPIU penalty, which does drive up our gross to net rates. We would expect in Q4 to get some relief on that CPIU. That's pretty consistent with what we've seen in previous quarters, but we were definitely at the high end for this quarter.

亞歷克，這位是查爾斯。所以，就毛利到淨利的比率而言，我們應該告訴大家，我們絕對達到了我們之前給出的 12% 到 15% 區間的上限。這與我們本季初的預期一致。正如您從先前的談話中了解到的，我們從 7 月 1 日起提高了價格，由此產生了 CPIU 罰款，這確實推高了我們的毛利率和淨利率。我們預期第四季CPIU方面會有所緩解。這與我們前幾季看到的情況基本一致，但本季我們絕對處於較高水準。

And again, this is Mike. With respect to the DAY301 program, we have a great group of investigators and the DAY301 program continues to move along nicely through -- not just dose escalation, but also the beginning of dose optimization and backfill cohort. So really no issues whatsoever there.

再次介紹一下，我是麥克。關於 DAY301 項目，我們擁有一支優秀的科研團隊，DAY301 項目也繼續順利推進——不僅推進了劑量遞增，還開始了劑量優化和補充隊列研究。所以真的沒有任何問題。

With respect to your broader question, I think I'd reframe it just a bit. I'm not so certain there's an issue at all with the target. In fact, I think the target is a really sound target for oncology development. There are distinctions between some of the other therapeutics against the target, especially with respect to payload. But we're focused, obviously, on our own program, which continues to progress nicely through its paces in early development.

關於你提出的更廣泛的問題，我想我會稍微換個方式表達。我不太確定目標是否有任何問題。事實上，我認為這個標靶對於腫瘤學開發來說是一個非常合理的標靶。針對該標靶的其他一些療法與其它療法存在區別，尤其是在有效載荷方面。但很顯然，我們專注於我們自己的項目，該項目在早期開發階段進展順利。

Okay, thank you very much.

好的，非常感謝。

Alec, one more statement, too, as I was reflecting on the greater portion of your question. One of the key things to remember too, in addition to the gross to net and trying to get to where I believe you're getting in your calculation is where we are with channel stock on hand during the quarter as well. And for this quarter, we were at the low end of our channel stock range. That was really a resulting -- that was really a result of the timing of when shipments occur and where the calendar fell, to be fair.

Alec，還有一點補充，因為我正在思考你問題的大部分內容。除了毛利到淨利的轉換，以及努力達到你計算出的結果之外，還需要記住的關鍵一點是，本季通路庫存情況也很重要。本季度，我們的通路庫存處於較低水準。公平地說，這實際上是發貨時間和日曆安排所導致的結果。

But it was really driven by a high level of demand this quarter given the high level of NPS, and the strong duration that we have. But when you're thinking through your calculation, definitely consider the low end of that range being there. We'll continue that 2 to 4 weeks of days on hand going forward, we are continuing with the guidance to internally working on that. But note that we are at the low end.

但本季強勁的需求確實是主要驅動因素，因為 NPS 水平很高，而且我們的產品持續時間也很長。但在進行計算時，一定要考慮到該範圍的下限。接下來我們將繼續保持 2 到 4 週的人員儲備，我們將繼續按照內部指導方針進行相關工作。但請注意，我們目前處於較低水平。

Okay. Very helpful color. Thank you.

好的。非常實用的顏色。謝謝。

Thanks, Alec.

謝謝你，亞歷克。

Kelsey Goodwin, Piper Sandler.

凱爾西·古德溫，派珀·桑德勒。

Oh hey, thanks for taking our question and Congrats on the quarter. Two from me. First, maybe just any commentary that you could provide in terms of how the patient population breaks down in terms of line of therapy? I know you had some commentary on increases in second-line specifically, but any color there?

嗨，謝謝你回答我們的問題，也恭喜你本季取得好成績。我投兩票。首先，您能否就患者群體在治療方案方面的組成提供一些評論？我知道你對第二線的成長有一些評論，但有什麼具體細節嗎？

And then second question. In terms of gaining uptake with a particular physician, how impactful do you think having the longer-term data is, for example, the ASCO data set versus the prescriber just gaining that firsthand experience? Thanks so much.

然後是第二個問題。就獲得特定醫生的認可而言，您認為擁有長期數據（例如 ASCO 數據集）與處方醫生獲得第一手經驗相比，哪種方式更有影響力？非常感謝。

Thanks for the questions, Kelsey. Good ones, and I'll ask Lauren to respond to.

謝謝你的提問，凱爾西。很好，我會請勞倫回覆。

Yes. Thank you for the questions. So from a line of therapy perspective, first, let me just say that from a primary data perspective, our view is limited. So we don't have a comprehensive data set to look at line of therapy. It's just the nature of our data. So we have to get it from other -- in other angles. And the way that we do that is through market research with physicians.

是的。謝謝大家的提問。所以從治療的角度來看，首先，我想說的是，從原始數據的角度來看，我們的視野是有限的。因此，我們沒有全面的數據集來研究治療方案。這就是我們數據的特性。所以我們必須從其他角度來看這個問題。我們實現這一目標的方式是透過對醫生進行市場調查。

So the data that I reported today was from self-reported physician prescribing behavior. And we have seen this over time. So over the past 12 months, increased significantly in what they are reporting as far as using OJEMDA in the second-line. So we've seen about 60% growth in their reporting of that. But that's the best data that we have at this point. And so that's the lens that we look at line of therapy through.

因此，我今天報告的數據來自醫生自我報告的處方行為。隨著時間的推移，我們已經看到了這一點。因此，在過去的 12 個月裡，他們報告的在二線治療中使用 OJEMDA 的情況顯著增加。因此，我們看到他們在相關報告方面成長了約 60%。但這是我們目前掌握的最佳數據。所以，這就是我們看待治療方案的視角。

To your question about uptake, it's very hard to split kind of physician behavior into the why they did that. So you were asking what's long-term data versus first-hand experience. I think it's always a combination of both. But when we're talking about the latest data that came out, the one that I wanted to mention not to underestimate is the ASCO data that was reported on growth velocity. So I do think that some physicians, although they may have believed in the efficacy, and I don't think that most of them were surprised by our efficacy update, it was consistent with what they expected.

關於您提出的接受度問題，很難將醫生的行為分解為他們這樣做的原因。所以你是在問，什麼是長期數據，什麼是第一手經驗。我認為總是兩者兼具。但說到最新公佈的數據，我想特別提一下，不要低估ASCO報告的生長速度數據。所以我認為，雖然有些醫生可能相信療效，而且我認為他們中的大多數人對我們的療效更新並不感到驚訝，這與他們的預期一致。

I do think that some of them may have been more cautious in using OJEMDA than even they would admit, because they had unanswered questions about growth velocity. That ASCO data set answered those questions. So it showed reversibility in the large majority of patients. And many of the physicians who saw that data reported to us that, that was meaningful to them. And then that really made them more confident in using OJEMDA in their patients. Did that answer your question?

我認為，他們中的一些人在使用 OJEMDA 時可能比他們自己承認的要謹慎得多，因為他們對增長速度還有一些未解之謎。ASCO 的資料集解答了這些問題。因此，在絕大多數患者中，病情都具有可逆性。許多看過這些數據的醫生告訴我們，這些數據對他們來說很有意義。這讓他們更有信心在患者身上使用 OJEMDA。這樣回答了你的問題嗎？

Yeah, that's perfect. Thank you so much.

對，那就太好了。太感謝了。

Ami Fadia, Needham & Company.

Ami Fadia，Needham & Company。

Hi, good afternoon. Thanks for taking my question and congrats on the nice quarter. My question is about the 3-year update that's coming up. And I heard sort of your remarks about at least in the EAP patients, you're seeing sort of a median of about 20 months of duration of use. With the three-year update coming up, do you think -- are you expecting to see some patients sort of -- or sort of that median go up in that study? Or is it more meant to inform when to restart treatment and inform growth velocity while the patient is sort of off treatment? So help us understand sort of what we should be focusing on when we see that data. And then separately, if I may -- I can stop and ask the second question later.

您好，下午好。感謝您回答我的問題，並祝賀您本季業績出色。我的問題是關於即將到來的三年一次的更新。我聽您提到，至少在 EAP 患者中，使用持續時間的中位數約為 20 個月。隨著三年更新即將到來，您認為——您是否預期會看到一些患者——或者說，該研究中的中位數會上升？或者，它的主要目的是告知何時重新開始治療，以及在患者停止治療期間的生長速度？所以請幫助我們理解，當我們看到這些數據時，我們應該專注於哪些方面。然後，如果可以的話——我可以稍後再問第二個問題。

No problem, Ami. Thanks for the question. So let me walk you through what we know today already from the FIREFLY-1 study and then what we're expecting from the 3-year data. And I'll ask Mike to add anything to my comments.

沒問題，阿米。謝謝你的提問。那麼，讓我帶您了解我們目前從 FIREFLY-1 研究中已經了解到的情況，以及我們對 3 年數據的預期。我會請麥克補充我的觀點。

So in the trial of FIREFLY-1, we know already that the median duration of treatment was just under 24 months. And we've known that for some time. And that's an important data point. That actually informed our expectation around what we may see as a median in the commercial setting. We're not there yet in the commercial setting, but we are for that EAP component, and that's why we reported out that 20-month median for the EAP cohort. And that's highly consistent with our expectations and benchmarks. So really encouraging.

因此，在 FIREFLY-1 的試驗中，我們已經知道治療的中位持續時間略低於 24 個月。我們早就知道這一點了。這是一個重要的數據點。這實際上影響了我們對商業環境中中位數的預期。在商業領域，我們還沒有達到目標，但在員工協助方案 (EAP) 方面，我們已經達到了目標，這就是為什麼我們報告了 EAP 隊列的 20 個月中位數。這與我們的預期和標準高度吻合。真是令人鼓舞。

For the 3-year data set, we're really focused on what happens as you follow patients out for longer periods of time. In particular, what we're focused on, as Mike noted earlier, are these time-to-event kind of end points. But to make it really simple, what we're really laser pointed on is what physicians have been asking us, which is what happens after you give patients 24 months of therapy of OJEMDA once they come off treatment. And they can come off for a bunch of reasons.

對於這 3 年的數據集，我們真正關注的是隨著對患者的長期追蹤觀察會發生什麼。正如麥克之前提到的，我們尤其關注的是這些事件發生的時間終點。但簡單來說，我們真正關注的是醫生一直在問我們的問題，那就是在病人接受 24 個月的 OJEMDA 治療後，停止治療後會發生什麼事。它們脫落的原因有很多。

It can be they simply want a break. It could be some focus on releasing that growth velocity delay. But regardless, in this physician community and in this patient population, there's always a desire to limit treatment if it's at all possible. And their specific question for us, there really are two, has been, one, do you see tumor rebound growth?

他們可能只是想休息一下。這可能是為了緩解成長速度延遲的問題。但無論如何，在這個醫生群體和這個患者群體中，總是希望盡可能地限制治療。他們向我們提出的具體問題，實際上有兩個，一是，你們是否觀察到腫瘤反彈增長？

Meaning short-term increases in the tumor growth right after you stop that therapy after 24 months. And the reason they're focused on that question is because of their observations reported to us, this is not published, but their own observations around what happens with MEK inhibitor treatment when you stop MEK inhibitor treatments. That's the first question they're interested in.

這意味著在 24 個月治療結束後停止治療，腫瘤生長會在短期內加速。他們之所以關注這個問題，是因為他們向我們報告了一些觀察結果，這些結果尚未發表，但他們觀察到，當停止 MEK 抑制劑治療時，MEK 抑制劑治療會發生什麼。這是他們最感興趣的第一個問題。

The second is independent of that growth rebound, do you also see stability of the tumor for a significant period of time after that 24-month treatment period. And the way they think about that is what do you see 1 year after you stop treatment. So patient is treated for 24 months and then followed for another year, what portion of those patients that have that three-year time horizon have required another therapy, and what patients have not required another therapy?

第二個問題與這種增長反彈無關，在 24 個月的治療期結束後，您是否也觀察到腫瘤在相當長的時間內保持穩定。他們的想法是，停止治療一年後你會看到什麼。如果患者接受 24 個月的治療，然後進行一年的隨訪，那麼在三年時間範圍內，有多少患者需要再次治療，又有多少患者不需要再次治療？

And what they report to us is that any percentage greater than about 50% not requiring therapy in that 1-year period is very encouraging. So that's what we're really focused on, Ami, at the 3-year data cut -- that you'll see at SNO. And I think that frames the two big things that we're looking at. I don't want to minimize the substance of what Mike also mentioned, which is the more detailed assessments of time to next therapy as well as treatment-free interval. Let me pause there. I know that's a lot.

他們向我們報告說，一年內不需要治療的比例超過 50% 左右，這非常令人鼓舞。所以，Ami，這就是我們在三年資料剪輯中真正關注的重點——你將在SNO上看到。我認為這概括了我們正在關注的兩件大事。我不想輕視麥克也提到的實質內容，那就是對下次治療時間以及無治療間隔進行更詳細的評估。我先停一下。我知道這很多。

Mike, anything you want to add?

麥克，你還有什麼要補充的嗎？

Thanks, Jeremy. Now the only thing I'd add is just please keep in mind that any measure of rebound growth of tumor or progression is really a sort of an early clinical surrogate for needing to intervene in some way in a disease where, as Jeremy mentioned, the balance of intervening with therapy versus managing the chronicity of the disease is very important. And so that's why this rebound question is clinically important, but really in the context of what's even more important, which is how long are patients off therapy and what's the interval before their next therapy.

謝謝你，傑瑞米。現在我唯一要補充的是，請記住，任何腫瘤反彈生長或進展的指標實際上都是需要對疾病進行某種幹預的早期臨床替代指標，正如傑里米提到的那樣，通過治療進行幹預與控制疾病的慢性化之間的平衡非常重要。所以，反彈問題在臨床上很重要，但更重要的是，患者停止治療的時間有多長，以及下一次治療的間隔時間有多長。

That was very helpful. My second question is just sort of around the commercial landscape and that Slide number 11 is quite helpful with understanding kind of the depth of prescribing. Can you give us a sense of what is sort of the concentration of patients in physician offices, when you're at, say, 9 plus patients, does that mean that you've sort of exhausted a big percentage of the number of patients that, that physician might be treating? Or is that still -- does it still mean that there's sort of a long way to go in terms of deepening that prescribing at that particular physician? Thank you.

那很有幫助。我的第二個問題是關於商業領域的，第 11 張投影片對於理解處方的深度非常有幫助。您能否為我們描述一下醫師診間病人的集中程度？比如說，當診間裡有 9 位以上的病人時，這是否意味著這位醫師已經接診了很大一部分病人？或者說，這是否仍然意味著，對於這位醫生來說，在深化處方方面還有很長的路要走？謝謝。

Sure. Ami, I'll let Lauren answer. But the short answer from my perspective is no, we're just scratching the surface, and this greater depth is fabulous, but there's a long way to go. But Lauren, maybe you can talk in more detail.

當然。阿米，我請勞倫來回答。但從我的角度來看，簡短的回答是：不，我們只是觸及了皮毛，這種更深層的探索固然很棒，但還有很長的路要走。但是勞倫，或許你可以說得更詳細。

Yes, I absolutely agree. So remember, there is variability as in any market with how many patients are at each account. That's why we have different priorities of accounts. You've heard us, in past calls, we didn't really talk about it much in this one, but in past calls that we have Priority 1, 2 and 3 accounts. A significant number of those 9 patient accounts are our Priority 1 accounts. They have a considerable volume of patients and have a lot more potential to prescribe. So we're not worried at all at this point of kind of capping out, the physicians report to us many more patients. And so we consider -- we continue to see opportunity.

是的，我完全同意。所以請記住，任何市場都會有差異，每個帳戶的患者數量也不例外。這就是為什麼我們對不同帳戶有不同的優先順序。你們在之前的電話會議中已經聽我們說過，雖然這次我們沒有過多提及，但我們之前說過我們有優先級 1、2 和 3 的帳戶。這 9 個患者帳戶中有相當一部分是我們的一級優先帳戶。他們擁有相當數量的患者，並且有更大的處方潛力。所以目前我們一點也不擔心會達到極限，醫生告訴我們還有很多病人。因此我們認為——我們仍然看到機會。

Thank you.

謝謝。

Andres Maldonado, HC Wainwright.

安德烈斯·馬爾多納多，HC·溫賴特。

Hi guys, thanks for taking my question and congrats on all the progress thus far. Two quick ones from us. I want to dig into a little bit the new patient starts as a key revenue driver. Obviously, the question is, do you guys view new patient -- all new patient starts as equal? And are you seeing differences in persistence or dose modification needs based on particularly the reason for switching, elective switch toxicity or progression?

大家好，感謝你們回答我的問題，也恭喜你們迄今為止的所有進展。我們先簡單介紹兩點。我想深入探討新患者是如何成為關鍵的收入驅動因素的。顯然，問題是，你們是否將所有新患者視為同等重要？您是否觀察到，根據轉換原因（例如選擇性轉換毒性或疾病進展）的不同，治療的持續性或劑量調整需求是否有差異？

And then the second question. On the FIREFLY-2 study, given that it includes rechallenge and crossover, curious how you're framing expectations on efficacy, if the crossover leads to a potential compression of the perceived delta versus standard of care for that study? Thank you very much for taking my questions.

然後是第二個問題。關於 FIREFLY-2 研究，鑑於它包括再次挑戰和交叉試驗，我很好奇您是如何設定療效預期的，如果交叉試驗可能導致該研究中感知到的與標準治療相比的差異被壓縮？非常感謝您回答我的問題。

Thanks, Andres. Let me ask Mike to start with your FIREFLY-2 question, and then we'll come back to the question about the commercial setting and Lauren can address.

謝謝你，安德烈斯。我先請 Mike 回答你關於《螢火蟲2》的問題，然後再回到關於商業環境的問題，讓 Lauren 來解答。

Thanks, Jeremy. Yes. Just a couple of key points to keep in mind with FIREFLY-2. The primary initial efficacy endpoint is objective response rate between the 2 study arms. And the primary time to event endpoint is a measure of progression. And so -- and the third point I'd make is that the opportunity to cross over, to receive tovorafenib is very tightly managed within both the study design and the operationalization of the study.

謝謝你，傑瑞米。是的。關於《螢火蟲2》，有幾點要注意。主要初始療效終點是兩個研究組之間的客觀緩解率。而事件終點的主要時間是衡量進展的指標。因此——我要提出的第三點是，交叉接受託沃拉非尼治療的機會在研究設計和研究實施過程中都得到了非常嚴格的控制。

So it's our expectation that, that component of the study -- first of all, it will be really helpful and meaningful data, clinical data that we'll generate with respect to the subset of patients that do receive tovorafinib after first-line treatment in that construct. But for the primary endpoints of the study, we don't really see any concern given the way that we've designed the study and operationalized its oversight.

因此，我們期望研究的這一部分——首先，它將產生真正有幫助且有意義的數據，即我們將針對在該結構中接受一線治療後接受託沃非尼治療的患者子集生成的臨床數據。但就研究的主要終點而言，鑑於我們設計研究的方式以及實施監督的方式，我們並不認為有任何擔憂。

Thanks, Mike.

謝謝你，麥克。

And then back to your NPS question. So first of all, NPS is a key revenue driver for us beyond the quarter, right? Because obviously, these patients stay on for long periods of time. So although they may start in this quarter, they actually have a greater impact in future quarters because they'll get 3 refills in a quarter as opposed to -- if they came on in the later half of the quarter, they don't get 3 this quarter, right? So NPS is important for our long-term trajectory.

然後再回到你關於NPS的問題。首先，NPS 是我們季度之外的關鍵收入驅動因素，對吧？因為很顯然，這些病人需要長時間住院。所以，雖然他們可能在本季度開始，但實際上他們在未來的幾個季度會產生更大的影響，因為他們在一個季度內可以獲得 3 次補貨，而如果他們是在本季度的後半段加入的，那麼他們在這個季度就無法獲得 3 次補貨，對吧？因此，NPS 對我們的長期發展軌跡至關重要。

Your question about whether they're all equal and dose modification, I would say, we look at patients by line. And so we do think that second-line is a more desirable place to be, number one, because the patient is likely less complicated from a health perspective. But secondly, because it's a larger pool of patients than the later lines, right? And so I would say that's how we're looking at patients. We're not really categorizing them in other ways. But to your point about dose modification, I just want to point out that our price is the same regardless of dose.

關於他們是否都一樣以及劑量調整的問題，我想說，我們按類別來考慮患者。因此，我們認為二線治療是一個更理想的選擇，首先是因為患者的健康狀況可能相對簡單。其次，因為這方面的患者群體比後續幾線患者群體更大，對吧？所以我覺得這就是我們看待病人的方式。我們並沒有用其他方式將它們分類。關於您提到的劑量調整問題，我想指出的是，無論劑量如何，我們的價格都是一樣的。

So actually, dose modification is an important part of AE management, and we see that patients that get dose modification actually do better. So we think that's an important thing for physicians to be comfortable doing and it doesn't, in any way, impact our bottom line -- our top line.

所以實際上，劑量調整是 AE 管理的重要組成部分，我們看到接受劑量調整的患者實際上效果更好。所以我們認為，醫生能夠輕鬆地做到這一點很重要，而且這絕對不會以任何方式影響我們的利潤——我們的收入。

Thank you very much. Great.

非常感謝。偉大的。

Thanks, Andres.

謝謝你，安德烈斯。

We have reached the end of the question-and-answer session, and this concludes today's conference. You may disconnect your lines at this time, and we thank you for your participation.

問答環節到此結束，今天的會議也到此結束。現在您可以斷開線路了，感謝您的配合。