Syndax Pharmaceuticals Inc (SNDX) 2025 Q2 法說會逐字稿

Good day, everyone, and welcome to the Syndax second quarter 2025 earnings conference call. Today's call is being recorded. (Operator Instructions).

大家好，歡迎參加 Syndax 2025 年第二季財報電話會議。今天的通話正在錄音。（操作員指令）。

At this time, I would like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.

現在，我想將電話轉給 Syndax Pharmaceuticals 投資者關係主管 Sharon Klahre。

Thank you, operator. Welcome, and thank you, all, for joining us today for a review of Syndax's second-quarter 2025 financial and operating Results. I'm Sharon Klahre, and with me today to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer; Steve Closter, Chief Commercial Officer; Dr. Nick Botwood, Head of R&D and Chief Medical Officer; Keith Goldan, Chief Financial Officer. Also joining us on the call today for question-and-answer session are Dr. Peter Ordentlich, Chief Scientific Officer; and Dr. Anjali Ganguli, Chief Strategy Officer.

謝謝您，接線生。歡迎並感謝大家今天加入我們，共同回顧 Syndax 2025 年第二季的財務與營運表現。我是 Sharon Klahre，今天與我一起介紹公司進展並討論財務結果的還有首席執行官 Michael Metzger、首席商務官 Steve Closter、研發主管兼首席醫療官 Nick Botwood 博士和首席財務官 Keith Goldan。今天參加電話會議問答環節的還有首席科學官 Peter Ordentlich 博士和首席策略官 Anjali Ganguli 博士。

This call is accompanied by a slide deck that has been posted on the Investor page of the company's website. You can now turn to our forward-looking statements on slide 2. Before we begin, I'd like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act 1995.

本次電話會議附有一份幻燈片，已發佈在公司網站的投資者頁面上。現在您可以翻到投影片 2 上的前瞻性聲明。在我們開始之前，我想提醒您，根據 1995 年《私人證券訴訟改革法案》的定義，本次電話會議中做出的任何非歷史性的陳述均被視為前瞻性陳述。

Actual results may differ materially from those indicated by the statements as a result of various important factors, including those discussed in the Risk Factors section in the company's most recent quarterly report on Form 10-Q as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, on August 4, 2025, only. A replay of this call will be available on the company's website, www.syndax.com, following its completion.

由於各種重要因素，包括公司最新的 10-Q 表季度報告以及向美國證券交易委員會提交的其他報告中「風險因素」部分所討論的因素，實際結果可能與聲明所示的結果存在重大差異。任何前瞻性陳述僅代表我們截至今天（2025 年 8 月 4 日）的觀點。在此次電話會議結束後，公司網站 www.syndax.com 上將提供此電話會議的重播。

And with that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

現在，我很高興將電話轉給 Syndax 執行長 Michael Metzger。

Thank you, Sharon, and good afternoon, and thank you, all, for joining us today. Starting with slide 3. First half of 2025 has been a transformational period for Syndax, marked by excellent commercial and pipeline execution. We are well positioned for rapid growth in the second half of 2025 and beyond with two first and best-in-class therapies with a combined market opportunity exceeding $10 billion.

謝謝你，莎倫，下午好，也謝謝大家今天加入我們。從投影片 3 開始。2025 年上半年是 Syndax 的轉型期，其特點是出色的商業和管道執行。我們擁有兩種首創且一流的療法，總市場機會超過 100 億美元，為 2025 年下半年及以後的快速成長做好了準備。

Revuforj and Niktimvo sales are growing with nearly $100 million in combined net product sales in the first half of the year, significantly exceeding expectations. Notably, Revuforj net revenue increased 43% quarter-over-quarter to $28.6 million, even with approximately 1/3 of patients pausing treatment to receive a stem cell transplant. Importantly, we are on the road to profitability with growing contributions from Revuforj and Niktimvo, a strong balance sheet, and an operating expense base that will remain stable for the next few years, while fully funding our strategic priorities.

Revuforj 和 Niktimvo 的銷售額不斷增長，今年上半年合計淨產品銷售額接近 1 億美元，大大超出預期。值得注意的是，儘管約有三分之一的患者暫停治療接受幹細胞移植，Revuforj 的淨收入仍較上季增加 43%，達到 2,860 萬美元。重要的是，我們正走在盈利的道路上，Revuforj 和 Niktimvo 的貢獻不斷增長，資產負債表強勁，營運費用基礎將在未來幾年保持穩定，同時為我們的策略重點提供充足的資金。

Looking to the future, our leadership in the menin space positions us to be first to the frontline and meaningfully expand the Revuforj franchise. We have a similarly compelling opportunity to bring Niktimvo into earlier lines of therapy and additional patient populations.

展望未來，我們在男性護理領域的領導地位使我們成為第一線的先驅，並顯著擴大 Revuforj 特許經營權。我們同樣擁有令人信服的機會，可以將 Niktimvo 引入早期治療領域並惠及更多患者群體。

Turning to slide 4. Let's dive into more detail on Revuforj, the first and only FDA-approved treatment for relapsed or refractory acute leukemia with a KMT2A translocation. The continued growth reflects strong uptake, the high unmet medical need and physicians' enthusiasm for Revuforj.

翻到幻燈片 4。讓我們更詳細地了解 Revuforj，這是 FDA 批准的第一個也是唯一一個用於治療 KMT2A 易位復發或難治性急性白血病的藥物。持續的成長反映了強勁的吸收量、巨大的未滿足醫療需求以及醫生對 Revuforj 的熱情。

It is clear following the recent presentations at ASCO and EHA that revumenib has a best-in-class profile with compelling activity across multiple genetic subtypes, including efficacy data in relapsed/refractory mutant NPM1 AML that surpassed any other results seen in the field. The breadth and strength of our clinical data will be the key to our success in acute leukemia, a market that is efficacy driven, given the severity of the disease.

從最近在 ASCO 和 EHA 上的報告可以清楚地看出，revumenib 具有同類最佳的特性，在多種基因亞型中均表現出令人信服的活性，包括復發/難治性突變 NPM1 AML 的療效數據，其療效超過了該領域的任何其他結果。我們的臨床數據的廣度和強度將是我們在急性白血病領域取得成功的關鍵，考慮到疾病的嚴重性，該市場是由療效驅動的。

As we look ahead, the outlook is very promising with multiple drivers that will further solidify our leading position and ensure sustained growth for many years to come. I will briefly highlight those drivers, and the team will provide additional details. First, patient identification and uptake has been strong. Since launch, we have already treated over 500 patients with Revuforj with approximately 90% of usage in KMT2A patients.

展望未來，前景十分光明，多重驅動因素將進一步鞏固我們的領先地位，確保未來多年的持續成長。我將簡要介紹這些驅動因素，團隊將提供更多詳細資訊。首先，患者識別和接受度很高。自推出以來，我們使用 Revuforj 治療了 500 多名患者，其中約 90% 用於治療 KMT2A 患者。

In just seven months, we have already reached 1/4 of the 2,000 patients diagnosed with relapsed/refractory KMT2A acute leukemia each year. Based on the robust activity we have seen in this population and physician excitement around the drug, we expect the total number of patients treated with Revuforj to grow materially in future quarters, particularly as it is the only approved therapy for these patients.

僅用七個月的時間，我們就已經為每年確診為復發/難治性 KMT2A 急性白血病的 2,000 名患者中的 1/4 提供了治療。根據我們在該族群中看到的強勁活動以及醫生對該藥物的興奮，我們預計未來幾個季度接受 Revuforj 治療的患者總數將大幅增長，特別是因為它是這些患者唯一獲批的治療方法。

Second, Revuforj is increasingly being used in earlier lines of therapy. Emerging claims data showed that the use in KMT2A as of this quarter is already being concentrated in the second line. This trend is especially important in oncology because as patients are treated earlier, they generally have a higher response rate, a longer duration of response, and a higher chance of proceeding to a potentially curative stem cell transplant.

其次，Revuforj 在早期治療的應用越來越廣泛。新興的索賠數據顯示，截至本季度，KMT2A 的使用已集中在第二線。這一趨勢在腫瘤學中尤其重要，因為患者接受治療越早，他們的反應率通常越高，反應持續時間越長，並且進行潛在治癒性幹細胞移植的機會也越高。

Thus, as Revuforj is used earlier, we expect to see an increase in the average time on drug for all patients. We also expect to see a high rate of patients proceeding to transplant a higher rate of patients treating -- proceeding to transplant than was observed in our pivotal trial, which on average enrolled a later-line patient population. In fact, early indicators suggest that we are already seeing a meaningfully higher transplant rate in the commercial setting.

因此，隨著 Revuforj 的早期使用，我們預計所有患者的平均藥物時間都會增加。我們也預計，接受移植治療的患者比例將高於我們關鍵試驗中觀察到的比例，該試驗平均招募了後期患者群體。事實上，早期指標表明，我們已經看到商業環境中的移植率顯著提高。

Third is the group of patients receiving Revuforj post-transplant increases, it should substantially increase the overall duration of therapy. Notably, prescribing physicians tell us they plan to restart patients on Revuforj post-transplant for one to two years. Given the high risk of recurrence, both patients and physicians tell us they are eager to restart the therapy that induced remission, especially when the drug has an excellent tolerability profile.

第三，移植後接受 Revuforj 治療的患者群體增加，這應該會大幅增加治療的​​整體持續時間。值得注意的是，開處方的醫生告訴我們，他們計劃在移植後讓病人重新開始服用 Revuforj 一到兩年。鑑於復發風險高，患者和醫生都告訴我們，他們渴望重新開始誘導緩解的治療，特別是當藥物具有良好的耐受性時。

These three drivers position Revuforj to transform care for KMT2A patients from an acute treatment paradigm with survival measured in a few months to a more chronic disease with the potential to extend survival from months to years. Importantly, relapsed/refractory KMT2A acute leukemia is just the first opportunity for Revuforj.

這三個驅動因素使 Revuforj 能夠將 KMT2A 患者的治療從以幾個月為生存期的急性治療模式轉變為一種更慢性的疾病，有可能將生存期從數月延長至數年。重要的是，復發/難治性 KMT2A 急性白血病只是 Revuforj 的第一個機會。

In the near term, we anticipate both the inclusion of Revuforj in the clinical treatment guidelines and the approval of our supplemental new drug application, or sNDA, in relapsed/refractory mutant NPM1 AML. The anticipated approval of our sNDA, which was recently granted priority review and a signed a PDUFA action date of October 25, 2025, would expand our addressable population to over 6,000 patients across both genetic subtypes and increase the relapsed/refractory market opportunity for Revuforj in the US to $2 billion.

在短期內，我們預計 Revuforj 將被納入臨床治療指南，並且我們的補充新藥申請（sNDA）將獲得批准，用於治療復發/難治性突變型 NPM1 AML。我們的 sNDA 預計獲得批准，該申請最近獲得優先審查，並簽署了 PDUFA 行動日期為 2025 年 10 月 25 日，這將擴大我們的目標人群至兩種基因亞型的 6,000 多名患者，並將 Revuforj 在美國復發/難治性市場機會增加到 20 億美元。

Importantly, Revuforj is positioned to become the first and only menin inhibitor with a label that expands to mutant NPM1 and KMT2A translocated patients, both adults and children. Based on resounding KOL feedback, the expected breadth of our label will be a major competitive advantage. Looking to the future, we will further extend our leadership into the frontline setting, a US market opportunity exceeding $5 billion.

重要的是，Revuforj 將成為第一個也是唯一適用於突變型 NPM1 和 KMT2A 易位患者（包括成人和兒童）的 menin 抑制劑。根據 KOL 的強烈回饋，我們品牌的預期廣度將成為一大競爭優勢。展望未來，我們將進一步拓展我們的領導地位，進入前線市場，也就是價值超過 50 億美元的美國市場。

Enrollment is already ongoing in our frontline trial for patients unfit to receive intensive chemotherapy and start-up activities are well underway to initiate our trials in patients able to receive intensive chemotherapy. With Revuforj's best-in-class profile and a multiyear start into the market versus potential me-too competitors, we will maintain our dominant position in this multibillion-dollar market opportunity.

我們針對不適合接受強化化療的患​​者進行的第一線試驗的招募工作已在進行中，而針對能夠接受強化化療的患​​者開展試驗的啟動活動也正在順利進行中。憑藉 Revuforj 一流的產品形像以及多年來在市場上與潛在同類競爭對手的競爭優勢，我們將在這個價值數十億美元的市場機會中保持主導地位。

Shifting gears to slide 5 to Niktimvo, our first-in-class therapy for chronic graft-versus-host-disease, or GVHD. I am pleased to highlight a very successful first full quarter for sales with our partner, Incyte, reporting $36.2 million in net revenue. This is up significantly from $13.6 million in the first two months of the launch in Q1. The $50 million in net revenue generated in the first five months of the launch underscores the substantial opportunity in chronic GVHD.

切換到幻燈片 5，展示 Niktimvo，這是我們治療慢性移植物抗宿主疾病 (GVHD) 的首創療法。我很高興地強調，我們的合作夥伴 Incyte 的第一季銷售非常成功，淨收入達 3,620 萬美元。這一數字較第一季推出後的前兩個月的 1,360 萬美元大幅增長。該產品上市後的前五個月產生的 5,000 萬美元淨收入凸顯了慢性 GVHD 領域的巨大機會。

Importantly, Niktimvo is already profitable to Syndax with our 50% share of the Niktimvo product contribution amounting to $9.4 million for the second quarter. As sales continue to ramp, the cash flow contributions to Syndax from Niktimvo will only grow in significance.

重要的是，Niktimvo 已經為 Syndax 帶來了利潤，我們持有 Niktimvo 產品 50% 的份額，第二季貢獻金額達 940 萬美元。隨著銷售額的持續成長，Niktimvo 對 Syndax 的現金流貢獻將越來越大。

With initial Niktimvo sales tracking with the early benchmarks set by REZUROCK, another product approved in the third-line chronic GVHD setting now annualizing at more than $500 million in the US, within three years of its launch. We are confident that Niktimvo will be a critical component of our success for many years to come.

Niktimvo 的初始銷售額與 REZUROCK 設定的早期基準持平，REZUROCK 是另一種獲準用於治療慢性 GVHD 的三線產品，上市三年內，其年銷售額在美國已超過 5 億美元。我們相信，Niktimvo 將成為我們未來多年成功的關鍵因素。

Finally, before I hand the call over to the team, I would like to highlight that we also strengthened our leadership team this quarter with the addition of Dr. Nick Botwood as Head of R&D and Chief Medical Officer. Nick is a medical oncologist by training, with over 25 years of experience leading the development and global commercialization of novel oncology medicines, including blockbuster drugs such as Opdivo and Yervoy, during his time at BMS.

最後，在我將電話交給團隊之前，我想強調的是，本季我們也加強了領導團隊，新增了 Nick Botwood 博士擔任研發主管和首席醫療官。Nick 是一名受過訓練的腫瘤內科醫生，在 BMS 任職期間，擁有超過 25 年的領導新型腫瘤藥物開發和全球商業化經驗，包括 Opdivo 和 Yervoy 等重磅藥物。

I would also like to thank Bill Meury for his seven years of service on our Board and congratulate him on his new role as CEO of Incyte, our partner for Niktimvo. Bill has been an invaluable member of our Board as we developed and launched both drugs, and we look forward to working closely with him and the Incyte team as we continue to unlock Niktimvo's value.

我還要感謝 Bill Meury 在我們董事會任職七年，並祝賀他擔任我們 Niktimvo 合作夥伴 Incyte 的執行長。在我們開發和推出這兩種藥物的過程中，比爾一直是我們董事會中不可或缺的成員，我們期待與他和 Incyte 團隊密切合作，並繼續釋放 Niktimvo 的價值。

And with that, I will turn the call over to Steve to discuss our commercial progress in more detail. Steve?

說完這些，我將把電話轉給史蒂夫，讓他更詳細地討論我們的商業進展。史蒂夫？

Thank you, Michael. Let's dive right into our commercial updates on Revuforj and Niktimvo, starting with Revuforj on slide 6. As Michael said, the launch is going very well with net revenue for the second quarter increasing 43% quarter-over-quarter to nearly $29 million and $56 million generated over the first seven months of the launch.

謝謝你，麥可。讓我們直接了解 Revuforj 和 Niktimvo 的商業更新，從幻燈片 6 上的 Revuforj 開始。正如麥可所說，產品發布進展順利，第二季淨收入環比成長 43%，達到近 2,900 萬美元，發布後的前七個月淨收入達到 5,600 萬美元。

These impressive results are driven by multiple factors, including: a high unmet patient need; a robust stream of new patient starts over the quarter; expanding breadth and depth of prescribing; excellent formulary coverage; and a product in Revuforj that is delivering for patients.

這些令人印象深刻的成果是由多種因素推動的，包括：大量未滿足的患者需求；本季度新患者數量的強勁增長；處方廣度和深度的不斷擴大；出色的處方集覆蓋範圍；以及 Revuforj 中為患者提供服務的產品。

Physicians are observing excellent activity in clinical practice, Revuforj is rapidly becoming a standard of care in our indicated population. Over 1,300 prescriptions for Revuforj have been written for more than 500 patients from launch through the end of June. Just midway through the year, we have already penetrated 25% of the annual 2,000 patient incidents and are on track to penetrate 50% by year's end.

醫生在臨床實踐中觀察到了出色的活性，Revuforj 正在迅速成為我們針對的人群的護理標準。自 Revuforj 上市以來至 6 月底，已為 500 多名患者開出了 1,300 多張處方。光是今年年中，我們就已處理了每年 2,000 起病患事件中的 25%，並預計在年底前處理 50%。

Next, I'm excited to share some of the emerging data and customer feedback that provide important insights into the population of patients being treated with Revuforj, and bolster our confidence that the momentum we have seen since launch will continue well into the second half of the year and beyond.

接下來，我很高興與大家分享一些新興數據和客戶回饋，這些數據和回饋為了解接受 Revuforj 治療的患者群體提供了重要見解，並增強了我們的信心，即自推出以來看到的勢頭將持續到今年下半年及以後。

First, Revuforj is increasingly being used to treat patients earlier in their treatment journey. Early claims data show that 70% of Revuforj use has been concentrated in the second and third-line settings, with approximately 50% of use coming from that second line, which we can also call first relapse patients alone.

首先，Revuforj 越來越多地被用於在患者治療早期階段進行治療。早期索賠數據顯示，70% 的 Revuforj 使用集中在二線和三線環境中，其中約 50% 的使用來自第二線，我們也可以稱之為單獨的首次復發患者。

Second, we estimate that 1/3 of KMT2A patients treated with Revuforj have proceeded to transplant based on our analysis of medium to large academic institutions using Revuforj commercially. In contrast, one out of 4 KMT2A patients proceeded to transplant after treatment with Revuforj in AUGMENT-101, which enrolled a significant percentage of later line and heavily pretreated patients.

其次，根據我們對商業化使用 Revuforj 的大中型學術機構的分析，我們估計接受 Revuforj 治療的 KMT2A 患者中有 1/3 已經進行移植。相較之下，在 AUGMENT-101 研究中，四分之一的 KMT2A 患者在接受 Revuforj 治療後接受了移植手術，該研究招募了相當大比例的後期和接受過大量治療的患者。

It's important to understand that patients who ultimately proceed to transplant are typically treated with Revuforj for two to four months to ensure complete disease remission before pausing Revuforj for approximately three months to ensure engraftment of the transplant. Notably, physicians tell us they expect to put most, if not all, of their patients back on Revuforj post-transplant for one to two years.

重要的是要了解，最終進行移植的患者通常需要接受 Revuforj 治療兩到四個月，以確保病情完全緩解，然後暫停使用 Revuforj 約三個月，以確保移植的植入。值得注意的是，醫生告訴我們，他們預計大多數（如果不是全部）患者在移植後一到兩年內會重新服用 Revuforj。

In fact, in our clinical trial experience and compassionate-use program, we have already seen transplant patients who have been on Revuforj for one to two years and we were still on drug at the time of the data cutoff. Encouragingly, in the commercial setting we have started to see the first cohort of patients restart Revuforj. Based on a sampling of our accounts, we estimate that at least 1/3 of transplant patients have already restarted Revuforj, with that percentage expected to grow over time as more patients clear the engraftment period.

事實上，在我們的臨床試驗經驗和同情用藥計劃中，我們已經看到使用 Revuforj 一到兩年的移植患者，並且在數據截止時我們仍在使用藥物。令人鼓舞的是，在商業環境中，我們已經開始看到第一批患者重新開始使用 Revuforj。根據我們對帳戶的抽樣調查，我們估計至少有 1/3 的移植患者已經重新開始使用 Revuforj，隨著越來越多的患者完成植入期，這一比例預計會隨著時間的推移而增長。

As Revuforj continues to move earlier in the treatment paradigm, we expect this will translate to a significant increase in the average duration of therapy over time. Specifically, we expect the average treatment duration to build to four to six months in the first year of launch.

隨著 Revuforj 在治療模式中繼續向前發展，我們預計這將轉化為平均治療持續時間的顯著增加。具體來說，我們預計推出的第一年平均治療時間將增加到四到六個月。

According to our assessment of patients who started Revuforj shortly after launch, the average time on therapy is already well within the projected four to six-month range, and we expect this duration to expand to an average of six to 12 months as treatment patterns mature in the second year of launch.

根據我們對 Revuforj 上市後不久開始治療的患者的評估，平均治療時間已經遠遠在預計的四到六個月範圍內，並且我們預計，隨著上市第二年治療模式的成熟，這一持續時間將延長至平均六到十二個月。

I'd now like to briefly review some other metrics that underscore the strong position we're in for continued growth in KMT2A, and our anticipated launch into relapsed/refractory mutant NPM1 AML. First, we have a broad and growing prescriber base. From launch through the end of June, we've penetrated 65% of our higher priority Tier 1 and Tier 2 accounts, up from 44% of accounts at the end of last quarter and continuing to grow into the third quarter.

現在，我想簡要回顧一下其他一些指標，這些指標強調了我們在 KMT2A 領域持續成長的強勢地位，以及我們預期在復發/難治性突變 NPM1 AML 領域的投入。首先，我們擁有廣泛且不斷增長的處方者基礎。從推出到六月底，我們已經滲透了 65% 的高優先級第 1 層和第 2 層帳戶，高於上一季末的 44% 帳戶，並且持續增長到第三季。

These Tier 1 and Tier 2 accounts are the centers of excellence in the medium to large academic institutions, which represent 2/3 of the patient opportunity. Adoption is also increasing across all other tiers too, including in the community setting. Among all accounts that have ordered, the vast majority have ordered multiple times.

這些一級和二級帳戶是中大型學術機構的卓越中心，代表了 2/3 的患者機會。所有其他層面的採用率也在增加，包括社區環境。在所有下單的帳戶中，絕大多數都是多次下單。

Second, we have established excellent market access. Formulary coverage is now complete with more than 97% of all lives covered, including commercial, Medicare and Medicaid patients. Nearly all prescriptions are reimbursed with very few patients requiring our patient assistance program. The average time from prescription to first fill is less than four days, significantly faster than typical industry benchmarks.

第二，我們建立了良好的市場准入。藥方覆蓋範圍現已完整，涵蓋人數超過 97%，包括商業、醫療保險和醫療補助患者。幾乎所有處方都可報銷，只有極少數患者需要我們的患者援助計畫。從處方到首次配藥的平均時間不到四天，明顯快於典型的產業基準。

The best-in-class customer service we are delivering, will be a key factor for our long-term competitive immunity and brand loyalty. Notably, Revuforj performance is outperforming the early launch benchmarks set by other targeted AML therapies on key metrics, including revenue and prescriptions, patients treated activation accounts, as well as formulary coverage.

我們提供的一流客戶服務將成為我們長期競爭優勢和品牌忠誠度的關鍵因素。值得注意的是，Revuforj 在關鍵指標（包括收入和處方、患者治療激活帳戶以及處方集覆蓋範圍）上的表現優於其他靶向 AML 療法設定的早期發布基準。

Further, all indicators give us confidence that Revuforj is delivering for patients, and that we are well positioned to develop this medicine into an industry-leading franchise with a market opportunity exceeding $5 billion across the relapsed/refractory and frontline setting, as outlined on slide 7.

此外，所有指標都讓我們相信 Revuforj 能夠為患者帶來益處，並且我們有能力將這種藥物發展成為行業領先的特許經營產品，其在復發/難治性和一線治療領域的市場機會超過 50 億美元，如幻燈片 7 所示。

Now turning to key Niktimvo metrics on slide 8. Since the beginning of the launch, over 4,000 infusions have been administered to an estimated 700 patients, representing approximately 10% of the third-line plus chronic GVHD total market. Of all the patients that had started Niktimvo, approximately 80% to 90% remain on therapy today.

現在轉到幻燈片 8 上的關鍵 Niktimvo 指標。自上市以來，已為約 700 名患者進行了超過 4,000 次輸液，約佔三線及慢性 GVHD 總市場的 10%。在所有開始使用 Niktimvo 的患者中，約有 80% 至 90% 至今仍在接受治療。

More than 80% of all bone marrow transplant centers in the US are using Niktimvo, reflecting solid execution and the strong commercial synergies Niktimvo has with both companies' product portfolios. Importantly, Niktimvo is poised for further growth given the high unmet need in the chronic GVHD space and the positive experience physicians and patients are having with the drug.

美國超過 80% 的骨髓移植中心都在使用 Niktimvo，這反映了 Niktimvo 的穩健執行以及與兩家公司產品組合之間強大的商業協同效應。重要的是，鑑於慢性 GVHD 領域未滿足的需求以及醫生和患者對該藥物的積極體驗，Niktimvo 有望實現進一步成長。

Physicians are reporting rapid and durable improvements across organ systems, including some of the most difficult-to-treat organs like the lungs and skin. These observations align with the results we demonstrated in our pivotal trial and highlight Niktimvo's unique ability to address both fibrosis and inflammation, hallmarks of the condition.

醫生報告稱，器官系統得到了快速且持久的改善，包括一些最難治療的器官，如肺和皮膚。這些觀察結果與我們在關鍵試驗中證明的結果一致，並凸顯了 Niktimvo 治療纖維化和發炎（該疾病的標誌）的獨特能力。

As shown on slide 9, Niktimvo has a multibillion-dollar market opportunity. Our current indication allows us to target the 6,500 chronic GVHD patients in the US who require three or more lines of therapy. This represents a $2 billion total addressable market, assuming an average treatment duration of 12 months, which could be conservative given the chronic nature of the disease and the tolerability of Niktimvo.

如投影片 9 所示，Niktimvo 擁有數十億美元的市場機會。我們目前的適應症使我們能夠針對美國需要三種或更多種療法的 6,500 名慢性 GVHD 患者。假設平均治療時間為 12 個月，這意味著總潛在市場規模為 20 億美元，但考慮到疾病的慢性性質和 Niktimvo 的耐受性，這個數字可能比較保守。

Notably, in our clinical trial experience, we have seen some patients stay on therapy for more than three years. To summarize, we are very pleased with the progress we've made with both Revuforj and Niktimvo. Early indicators for both launches drive our confidence in continued growth and expansion with both products.

值得注意的是，在我們的臨床試驗經驗中，我們發現有些患者接受治療的時間超過三年。總而言之，我們對 Revuforj 和 Niktimvo 所取得的進展感到非常滿意。這兩款產品的早期發布指標增強了我們對持續成長和擴張的信心。

With that, I'll hand the call over to Nick.

說完這些，我就把電話交給尼克。

It's a pleasure to be on the call today, and to have the opportunity to build upon the exceptional work that Syndax has done pioneering two new therapeutic approaches. Starting on slide 10 with Revuforj or revumenib, an asset which has the potential to become the menin inhibitor of choice across the breadth of menin-driven acute leukemias. In the second quarter, we advanced our leadership position with a strong presence at EHA and ASCO, including two important publications.

我很高興今天能參加電話會議，並有機會在 Syndax 開創兩種新療法的基礎上繼續努力。從幻燈片 10 開始，Revuforj 或 revumenib 是一種有潛力成為治療由 menin 驅動的急性白血病的首選 menin 抑制劑的藥物。在第二季度，我們憑藉在 EHA 和 ASCO 上的強勢表現（包括兩份重要出版物）提升了我們的領導地位。

At EHA, we and our collaborators presented the latest data from AUGMENT-101 and the BEAT AML trial. I'd like to highlight two key takeaways from these. First, the AUGMENT-101 data demonstrate the breadth of revumenib activity across relapsed/refractory mutant NPM1, KM2TA and NUP98r acute leukemias.

在 EHA，我們和我們的合作夥伴展示了 AUGMENT-101 和 BEAT AML 試驗的最新數據。我想強調其中的兩個關鍵要點。首先，AUGMENT-101 數據證明了 revumenib 對復發/難治性突變 NPM1、KM2TA 和 NUP98r 急性白血病的活性廣度。

Notably, in the pivotal NPM1 population, nearly half of the patients achieved an overall response. And in a subgroup analysis, a median overall survival of 23 months was observed among these responders. These data, along with the rate of CR/CRh and duration of CR/CRh, are encouraging results that really stand out in this population.

值得注意的是，在關鍵的 NPM1 族群中，近一半的患者獲得了整體反應。在亞組分析中，這些反應者的中位總存活期為 23 個月。這些數據以及 CR/CRh 率和 CR/CRh 持續時間都是令人鼓舞的結果，在這一人群中確實很突出。

The compelling results are particularly relevant as efficacy is paramount in patients with acute leukemia given the severity of disease and the need for improved outcomes. Data from the pivotal NPM1 population were recently published in Blood, an important milestone that makes these landmark results available to the clinical community.

這一令人信服的結果尤其具有現實意義，因為考慮到病情的嚴重程度和改善預後的需要，療效對於急性白血病患者來說至關重要。關鍵 NPM1 群體的數據最近發表在《Blood》雜誌上，這是一個重要的里程碑，使這些具有里程碑意義的成果可供臨床使用。

Turning now to NUP98r. Phase I data from the AUGMENT-101 trial show an overall response rate of 60% among five patients with relapsed/refractory NUP98r AML, which is an aggressive difficult-to-treat form of acute leukemia. While the sample size is small, physicians are encouraged by these data and further trials are underway that will evaluate revumenib in NUP98r as well as other acute leukemias associated with HOX upregulation.

現在轉向 NUP98r。AUGMENT-101 試驗的第一階段數據顯示，五名復發/難治性 NUP98r AML 患者的總體反應率為 60%，這是一種侵襲性強、難以治療的急性白血病。雖然樣本量很小，但這些數據讓醫生們感到鼓舞，目前正在進行進一步的試驗，以評估 revumenib 在 NUP98r 以及與 HOX 上調相關的其他急性白血病中的作用。

The compelling and consistent results observed with revumenib across these genetic subtypes highlights the potential for revumenib to transform the standard of care for potentially 50% or more of all patients with AML. Moving now to the second key takeaway. The BEAT AML data presented at EHA and simultaneously published in the Journal of Clinical Oncology, are encouraging.

在這些基因亞型中觀察到的令人信服且一致的結果凸顯了 revumenib 有可能改變 50% 或更多 AML 患者的治療標準。現在轉到第二個關鍵要點。在 EHA 上展示並同時在《臨床腫瘤學雜誌》上發表的 BEAT AML 數據令人鼓舞。

As a reminder, this is a Phase Ib trial evaluating revumenib in combination with venetoclax and azacitidine in newly diagnosed older patients with mutant NPM1 or KMT2A rearranged AML. The data support the combinability of revumenib with ven/aza in the frontline setting and the potential for the triplet to provide high rates of complete remission and MRD negativity, two treatment goals associated with improved clinical outcomes.

提醒一下，這是一項 Ib 期試驗，評估瑞伐他汀合併維奈克拉和阿扎胞苷治療新診斷的 NPM1 突變或 KMT2A 重排 AML 老年患者的療效。數據支持在一線治療中將 revumenib 與 ven/aza 結合使用，且三聯療法有可能提供較高的完全緩解率和 MRD 陰性率，這兩個治療目標與改善臨床結果相關。

The overall response rate was 88% and the complete remission rate was 67% in the 43-patient intent-to-treat population. Importantly, MRD negativity was 100% by centralized flow cytometry testing. Both the CR and MRD negativity compare very favorably to the historical rates reported in the VIALE-A trial of ven/aza.

在 43 名意圖治療患者中，整體反應率為 88%，完全緩解率為 67%。重要的是，透過集中流式細胞儀檢測，MRD 陰性率為 100%。CR 和 MRD 陰性結果與 ven/aza 的 VIALE-A 試驗中報告的歷史比率相比非常有利。

Looking ahead, we have revumenib publications and presentations planned at major upcoming medical congresses, including the anticipated presentation of the first real-world evidence before the end of the year. Given the strong clinical interest in real-world evidence, we are thrilled to be working with leading cancer centers and physicians to present outcomes for this new therapeutic class.

展望未來，我們計劃在即將舉行的大型醫學大會上發表有關 Revumenib 的出版物和演講，包括預計在年底前展示第一份真實世界證據。鑑於臨床對真實世界證據的強烈興趣，我們很高興能與領先的癌症中心和醫生合作，展示這個新治療類別的成果。

Turning now to slide 11, and our further work developing Revuforj and Niktimvo into industry-leading franchises, I want to highlight three key points. First, we are laser-focused on extending our leadership position in menin inhibition into the frontline setting. Enrollment is well underway in the pivotal EVOLVE-2 trial of revumenib in combination with ven/aza in newly diagnosed patients with mutant NPM1 or KMT2A rearranged AML, who are ineligible or unfit to receive intensive chemotherapy.

現在翻到第 11 張投影片，我們進一步將 R​​evuforj 和 Niktimvo 發展成為業界領先的特許經營權，我想強調三個關鍵點。首先，我們專注於將我們在男性抑制方面的領導地位擴展到前線環境。關鍵的 EVOLVE-2 試驗正在順利進行中，該試驗將 revumenib 與 ven/aza 聯合用於治療新診斷的 NPM1 突變或 KMT2A 重排 AML 患者，這些患者不符合或不適合接受強化化療。

EVOLVE-2 is a Phase III randomized, double-blind, placebo-controlled trial. This trial will have dual primary endpoints of complete remission and overall survival to support potential accelerated approval and full approval, respectively. While the trial is open to both NPM1 and KMT2A patients for enrollment, the primary efficacy analysis will be based on the NPM1 population.

EVOLVE-2 是一項 III 期隨機、雙盲、安慰劑對照試驗。該試驗將具有完全緩解和總體生存這兩個主要終點，分別支持潛在的加速批准和完全批准。雖然該試驗對 NPM1 和 KMT2A 患者開放，但主要療效分析將基於 NPM1 族群。

This is the population that is more commonly ineligible for intensive chemotherapy due to advanced age or other comorbidities, unlike the KMT2A population which tends to be younger and fit enough for intensive chemotherapy. We are conducting this trial in partnership with the HOVON Group, a leading clinical trial cooperative known for executing clinical trials that deliver practice-changing data in hematology.

由於高齡或其他合併症，這類族群通常不適合接受強化化療，而 KMT2A 族群則往往較年輕，身體狀況足以接受強化化療。我們正在與 HOVON 集團合作進行這項試驗，HOVON 集團是一家領先的臨床試驗合作社，以執行提供血液學實踐改變數據的臨床試驗而聞名。

Second, in the newly diagnosed fit population, study start-up activities are well underway for two randomized placebo-controlled (Inaudible) studies of revumenib in combination with intensive chemotherapy followed by maintenance. We have named these the REVEAL trials.

其次，在新診斷的健康族群中，兩個隨機安慰劑對照（聽不清楚）研究的啟動活動正在順利進行，研究對象為 revumenib 合併強化化療及維持治療。我們將這些試驗命名為 REVEAL 試驗。

One trial is designed for patients with an NPM1 mutation and one for patients with [KMT2A] rearrangements. We expect to initiate in the fourth quarter of 2025. In the NPM1 population, the study will have dual primary endpoints of MRD negative CR and event-free survival, as these are important clinical endpoints in this population, and could have the potential to support accelerated approval and full approval, respectively.

一項試驗針對患有 NPM1 突變的患者，另一項試驗針對患有 [KMT2A] 重排的患者。我們預計將於 2025 年第四季啟動。在 NPM1 族群中，該研究將具有 MRD 陰性 CR 和無事件存活期雙重主要終點，因為這些是該族群中重要的臨床終點，並且可能分別支持加速批准和完全批准。

We expect that high awareness of Revuforj and positive experience in the clinic will drive rapid enrollment across our frontline programs. In support of our trials in the fit population, we are also looking forward to reporting Phase I data in newly diagnosed patients treated with revumenib and intensive chemotherapy in the fourth quarter of the year.

我們預計，Revuforj 的高認知度和臨床的積極體驗將推動我們一線計畫的快速招生。為了支持我們在健康人群中的試驗，我們也期待在今年第四季報告接受 revumenib 和強化化療治療的新診斷患者的第一階段數據。

Lastly, I want to highlight the work underway to develop Niktimvo, or axatilimab, for additional patient populations. In partnership with Incyte, several important trials are well underway, including a Phase II trial studying axatilimab in combination with ruxolitinib and a Phase III placebo-controlled registration-directed trial investigating axatilimab in combination with steroids. Beyond chronic graft-versus-host disease, we have an ongoing Phase II placebo-controlled trial called MAXPIRe, which is studying axatilimab in idiopathic pulmonary fibrosis, or IPF.

最後，我想強調目前正在進行的為更多患者群體開發 Niktimvo（或稱為 axatilimab）的工作。與 Incyte 合作，幾項重要試驗正在順利進行，包括研究阿沙替利單抗與蘆可替尼聯合使用的 II 期試驗，以及研究阿沙替利單抗與類固醇聯合使用的 III 期安慰劑對照註冊指導試驗。除了慢性移植物抗宿主疾病之外，我們還在進行一項名為 MAXPIRe 的 II 期安慰劑對照試驗，該試驗正在研究阿沙替利單抗在特發性肺纖維化（IPF）的療效。

Enrollment is proceeding very well, and we are on track to complete enrollment in the fourth quarter of this year, with top line data anticipated in the second half of 2026. We are optimistic about the potential for axatilimab in IPF and beyond, given the strong mechanistic rationale and preclinical evidence, along with the remarkable lung response observed in the AGAVE-201 trial.

招生工作進展順利，我們預計在今年第四季完成招生，預計在 2026 年下半年獲得頂線數據。鑑於強有力的機制原理和臨床前證據，以及在 AGAVE-201 試驗中觀察到的顯著肺部反應，我們對阿沙替利單抗在 IPF 及其他疾病中的潛力持樂觀態度。

Thank you, Nick. Earlier this afternoon, we reported detailed second quarter 2025 financial results, and I'll touch on a few of these key points on slide 12. For the second quarter of 2025, we reported Revuforj net revenue of $28.6 million. Quarter-over-quarter sales growth was driven by demand, as inventory levels remained stable to the first quarter at two to three weeks. We expect quarterly growth to meaningfully accelerate over the next year with the potential approval in NPM1, as well as the benefit of a longer duration of treatment in KMT2Ar acute leukemia.

謝謝你，尼克。今天下午早些時候，我們報告了 2025 年第二季的詳細財務業績，我將在第 12 張投影片上談論及其中的一些要點。2025 年第二季度，Revuforj 淨收入為 2,860 萬美元。季比銷售成長是由需求推動的，因為庫存水準與第一季相比保持穩定，為兩到三週。我們預計，隨著 NPM1 的潛在批准以及 KMT2Ar 急性白血病治療時間延長的好處，明年季度增長將顯著加速。

Also in the second quarter, Incyte reported Niktimvo net revenue of $36.2 million with inventory accounting for less than 5% of sales. Syndax reported $9.4 million in Niktimvo collaboration revenue after deducting the cost of sales and commercial expenses. Importantly, Niktimvo is already a positive cash flow contributor to Syndax in just its first full quarter of sales.

此外，在第二季度，Incyte 報告 Niktimvo 的淨收入為 3,620 萬美元，庫存佔銷售額的不到 5%。Syndax 報告稱，扣除銷售成本和商業費用後，Niktimvo 合作收入為 940 萬美元。重要的是，Niktimvo 在 Syndax 第一個完整銷售季度就已成為其正現金流貢獻者。

We expect the Niktimvo margin contribution, defined as collaboration revenue recorded by Syndax, as a percentage of Niktimvo net sales to be in the 20% to 30% range in the near term, and we anticipate this will improve longer term as sales grow and the partnership leverages a largely fixed expense base.

我們預計 Niktimvo 的利潤貢獻（定義為 Syndax 記錄的合作收入）佔 Niktimvo 淨銷售額的百分比在短期內將在 20% 到 30% 之間，並且我們預計，隨著銷售額的增長和合作夥伴關係利用基本固定的費用基礎，這一比例將在長期內得到改善。

We expect continued sales growth given GVHD remains a chronic disease, where there is a high response rate to Niktimvo and the average patient will likely remain on therapy for years. R&D expense was $62.2 million in 2Q with the increase versus the comparable prior year, driven by costs related to ongoing trials and increased activities to support commercialization.

鑑於 GVHD 仍然是一種慢性疾病，我們預計銷售額將持續成長，而 Niktimvo 的反應率很高，並且普通患者可能會繼續接受多年的治療。第二季研發費用為 6,220 萬美元，較去年同期有所增加，主要原因是正在進行的試驗相關成本以及支持商業化活動的增加。

SG&A expense was $43.8 million, with the increase versus the comparable prior year driven by costs related to the US commercial launch of Revuforj. With regard to expenses, you can find our guidance for the third quarter of 2025 and full year in the press release we issued today. Notably, we announced today that we expect our operating expenses to remain stable over the next few years.

銷售、一般及行政費用為 4,380 萬美元，與去年同期相比有所增加，原因是與 Revuforj 在美國商業發布相關的成本。關於費用，您可以在我們今天發布的新聞稿中找到我們對 2025 年第三季和全年的指導。值得注意的是，我們今天宣布，我們預計未來幾年我們的營運費用將保持穩定。

Turning to the balance sheet. We continue to maintain a strong financial position with $518 million in cash, equivalents and short and long-term investments as of June 30th. As I've said in the past, and I reiterate today, we expect Syndax will reach profitability with current funds on hand. In fact, my confidence is higher today given both drugs are outperforming our original forecasts.

轉向資產負債表。截至 6 月 30 日，我們繼續保持強勁的財務狀況，擁有 5.18 億美元的現金、等價物以及短期和長期投資。正如我過去所說的，今天我再次重申，我們預計 Syndax 將利用現有資金獲利。事實上，鑑於這兩種藥物的表現都超出了我們最初的預測，我今天的信心更高了。

We are confident we can execute commercially and also deliver on our integrated clinical development plans for both drugs while keeping operating expenses at today's levels. Our combined cash with increasing Revuforj and Niktimvo cash flow contributions alongside a fixed expense base, will drive our path to profitability.

我們有信心，我們可以在保持營運費用在當前水平的同時，實現這兩種藥物的商業化和綜合臨床開發計劃。我們的現金加上不斷增加的 Revuforj 和 Niktimvo 現金流貢獻以及固定的支出基礎，將推動我們走向獲利。

Turning the call back over to Michael.

將電話轉回給邁克爾。

Thank you, Keith. Before we move to Q&A, I want to take a moment on slide 13 to reiterate how well positioned Syndax is as a company. Revuforj and Niktimvo are outperforming expectations as strong physician enthusiasm drives robust adoption. We have a very sizable cash balance that will allow us to control our destiny and achieve sustained profitability with what we know are two dominant products in multibillion-dollar markets.

謝謝你，基斯。在我們進入問答環節之前，我想花點時間在第 13 張投影片上重申 Syndax 作為一家公司的良好定位。Revuforj 和 Niktimvo 的表現超乎預期，因為醫生的熱情推動了其大力採用。我們擁有非常可觀的現金餘額，這將使我們能夠掌控自己的命運，並憑藉我們所知的數十億美元市場中的兩種主導產品實現持續盈利。

A few key points to recap on Revuforj. Revuforj is the only FDA-approved therapy for KMT2A patients, and we have already identified and treated over 500 patients since launch, with 90% of those being on label. Physicians are treating earlier relapsed/refractory patients, which portends more favorable outcomes.

回顧 Revuforj 的幾個關鍵點。Revuforj 是唯一獲得 FDA 批准的針對 KMT2A 患者的療法，自推出以來我們已經識別並治療了 500 多名患者，其中 90% 符合標籤要求。醫生正在治療早期復發/難治性患者，這預示著更有利的結果。

Revuforj is getting patients to transplant at an even higher rate than what was observed in our clinical trials. Physicians are eager to put their patients back on Revuforj post-transplant, and we have begun to see evidence this is happening.

Revuforj 讓患者接受移植的比例甚至比我們在臨床試驗中觀察到的比例還要高。醫生們渴望讓病人在移植後重新使用 Revuforj，我們已經開始看到這種情況正在發生的證據。

Further, all key indicators of demand remained strong in July, which gives us confidence in the continued momentum of this launch. Ultimately, in the future, KMT2A patients on Revuforj and with the aid of transplant, will likely remain on drug for one year or more, with the best hope of improved survival. In the near term, we are poised to expand into relapsed/refractory mutant NPM1 AML, pending the FDA's anticipated approval of our sNDA.

此外，7月所有關鍵需求指標依然強勁，這使我們對此次發布的持續勢頭充滿信心。最終，在未來，接受 Revuforj 治療並在移植的幫助下，KMT2A 患者可能會繼續服藥一年或更長時間，並有望提高存活率。短期內，我們準備擴展到復發/難治性突變 NPM1 AML，等待 FDA 對我們的 sNDA 的預期批准。

Additionally, we are extending our leadership position to the front line with enrollment already under -- well underway in our first pivotal frontline trial. It is important to keep in mind that acute leukemia is an efficacy-driven market, and it is clear that Revuforj is a highly effective therapy with a favorable safety and tolerability profile.

此外，我們正在將我們的領導地位延伸到前線，我們的第一個關鍵前線試驗的招募工作已經在順利進行中。重要的是要記住，急性白血病是一個療效驅動的市場，很明顯，Revuforj 是一種具有良好安全性和耐受性的高效療法。

Finally, I will also note that we've retained worldwide rights to Revuforj and patent protection continues through at least the late 2030s. Turning to a few key points on Niktimvo. In collaboration with our partners at Incyte, the leaders in GVHD, the Niktimvo launch is off to an exceptional start. It is well positioned for growth in the $2 billion market for third-line chronic GVHD treatments with patent protection extending to the late 2030s.

最後，我還要指出的是，我們保留了 Revuforj 的全球權利，專利保護至少將持續到 2030 年代末。談談 Niktimvo 的幾個關鍵點。透過與 GVHD 領域的領導者 Incyte 的合作，Niktimvo 的推出取得了非凡的開端。該公司在價值 20 億美元的三線慢性 GVHD 治療市場中佔據有利地位，其專利保護期將延長至 2030 年代末。

Niktimvo provides a novel option in a market that needs new mechanisms of action. Patients initiating therapy may continue drug for years. We and Incyte continue to advance development programs designed to bring this drug into earlier lines of chronic GVHD therapy and other diseases, starting with IPF.

Niktimvo 為需要新作用機制的市場提供了一種新穎的選擇。開始治療的患者可能會繼續服藥數年。我們和 Incyte 繼續推進開發計劃，旨在將這種藥物應用於慢性 GVHD 治療和其他疾病的早期治療，首先是 IPF。

Niktimvo's financial contribution to Syndax is already profitable in its first full quarter. This will grow materially as sales ramp and operating margins continue to expand. Syndax has never been in a stronger position than we are today, and I look forward to sharing additional progress with you in the months ahead.

Niktimvo 對 Syndax 的財務貢獻在其第一個完整季度就已經實現盈利。隨著銷售額的成長和營業利潤率的不斷擴大，這一數字將大幅成長。Syndax 的地位從未像今天這樣強大，我期待在未來幾個月與大家分享更多進展。

As always, I want to close by thanking everyone who has supported us on this journey, including most importantly, the patients and families who have placed their trust in us, as well as our dedicated Syndax employees and long-term investors.

像往常一樣，最後我要感謝所有在這段旅程中支持我們的人，其中最重要的是信任我們的患者和家屬，以及我們敬業的 Syndax 員工和長期投資者。

And with that, I would like to open the call for questions. Operator?

現在，我想開始提問。操作員？

(Operator Instructions).

（操作員指令）。

Anupam Rama, JPMorgan.

摩根大通的 Anupam Rama。

Hey guys, thanks so much for taking the question. Just wanted to ask a question about this path to profitability. Keith, I know you mentioned operating expenses staying stable over the next couple of years. But what are you assuming in terms of the top line, in terms of treatment settings for Revuforj and Niktimvo?

嘿夥計們，非常感謝你們回答這個問題。只是想問一個有關獲利之路的問題。基思，我知道您提到未來幾年營運費用將保持穩定。但是，就 Revuforj 和 Niktimvo 的治療設定而言，您對頂線有何假設？

Can you get to profitability on sort of the refractory settings alone? Is there some sort of assumptions on frontline expansion baked into getting to profitability? How should we be thinking about that?

僅憑耐火材料設定就能獲利嗎？在實現獲利的過程中是否存在一些關於第一線擴張的假設？我們該如何思考這個問題？

Anupam, thanks for the question. We have been pretty consistent since November that we expect to get to profitability with the existing resources that we have today. And I would say the only thing that's changed since then is that we have two launches that are both outperforming our expectations.

Anupam，謝謝你的提問。自 11 月以來，我們一直堅信，我們有望利用現有資源來實現盈利。我想說，自那時以來唯一改變的是，我們推出的兩款產品都超出了我們的預期。

So the new disclosure that we provided today, stable operating expenses for the foreseeable future, say, the next two to three years, we're doing that because we want to give the buy-side and sell-side, we want to give the street the appropriate data for them to model our business better, so you guys can get to the same answer that we're getting to.

因此，我們今天提供的新披露是，在可預見的未來（例如未來兩到三年）保持穩定的營運費用，我們這樣做是因為我們希望為買方和賣方提供適當的數據，以便他們更好地模擬我們的業務，這樣你們就可以獲得與我們相同的答案。

We're not giving revenue guidance per se, Anupam, but I will say that given the timelines to get to approval in the frontline setting, you can definitely assume that we are getting to profitability on the relapsed/refractory indications alone. And I think, I just want to add, the guidance that we are giving, stable operating expenses, is not to be taken as we are taking our foot off the gas pedal, because we're not.

我們本身並沒有提供收入指導，Anupam，但我要說的是，考慮到在前線環境中獲得批准的時間表，你絕對可以假設我們僅憑復發/難治性適應症就能實現盈利。我想補充一點，我們給予的指導，即穩定的營運費用，不應該被理解為我們在放鬆油門，因為我們並沒有這樣做。

The modeling that we've done allow us to fully invest in the continuing successful launches of two products, executing commercially, but additionally, executing our integrated clinical development plan, as Nick talked about, both for Revuforj and Niktimvo.

我們所做的建模使我們能夠充分投資於兩種產品的持續成功推出，進行商業執行，此外，還執行我們的綜合臨床開發計劃，正如 Nick 談到的，針對 Revuforj 和 Niktimvo。

So, I think we're in a pretty unique position to control our own destiny. We have two launches that are both outperforming and a stable expense base. And the team has worked extremely hard to put ourselves in this position to specifically reward our shareholders for their investment. So, thanks for the question.

所以，我認為我們處於一個非常獨特的位置，可以掌控自己的命運。我們推出的兩款產品均表現出色，且費用基礎穩定。我們的團隊付出了極大的努力，才讓我們處於這樣的位置，以特別獎勵股東的投資。謝謝你的提問。

Thanks so much for taking the question.

非常感謝您回答這個問題。

Corinne Johnson, Goldman Sachs

高盛的科琳·約翰遜

This is Kevin Strang on for Corinne. I had a quick question on the patients moving on to transplant. After how many cycles is that typically occurring? And for patients that are going back on drug, you said that it was about 1/3 of patients so far. What are your expectations for the ultimate proportion of patients that will move on to maintenance therapy? And is this something you'll report quarterly?

我是 Kevin Strang，為 Corinne 報道。我有一個關於接受移植手術的病人的簡短問題。通常經過多少週期才會發生這種情況？至於重新服用藥物的患者，您說到目前為止大約佔總患者的 1/3。您對最終進入維持治療的患者比例有何預期？這是你們每季都會報告的事情嗎？

Kevin, thanks for your questions. So, look, I think we're very encouraged by what we're seeing with patients going to transplant. As we had noted early on when we first started developing this drug, patients do respond very quickly to revumenib, and that's usually within the first few cycles.

凱文，謝謝你的提問。所以，我認為，看到患者接受移植的情況，我們感到非常鼓舞。正如我們在開始開發這種藥物時就注意到的那樣，患者對 revumenib 的反應確實非常快，通常是在最初的幾個週期內。

That generally is preceded by a transplant thereafter. And that transplant can happen very quickly. It can happen within a couple of weeks. That's usually for KMT2A patients, a goal to get them to transplant as quickly as possible. So, a few cycles, certainly two to three, getting into remission, moving to transplant. That's how it generally works.

這通常先於移植。而且移植可以很快完成。這可能在幾週內發生。這通常針對的是 KMT2A 患者，目標是讓他們盡快接受移植。因此，經過幾個週期，肯定是兩到三個週期，病情就會緩解，然後進行移植。它通常就是這樣運作的。

We do see in our trial in our commercial experience, rather, about 1/3 of patients getting to transplant. We expect that number to accelerate. And the reason for that is we are treating patients earlier and earlier in the treatment paradigm. Physicians had told us they would put patients on Revuforj in sort of second line or first relapse.

在我們的商業經驗試驗中，我們確實看到大約 1/3 的患者接受了移植。我們預計這個數字還會加速成長。原因在於我們在治療模式中越來越早地對患者進行治療。醫生告訴我們，他們會讓病人在二線治療或第一次復發時使用 Revuforj。

We see the vast majority of our patients being treated now in second and third line, which is a great outcome for them, generally means patients do stay on drug longer, do better and have a better chance of going to transplant. So we do think that, that 1/3 number could go up from here, and we expect it too. And ultimately, we will continue to track this over time. It's early days in the launch, and we do expect to report on that metric at some point going forward.

我們看到絕大多數患者現在都在接受二線和三線治療，這對他們來說是一個很好的結果，通常意味著患者可以服用藥物更長時間，情況更好，並且有更好的機會進行移植。因此，我們確實認為，1/3 的數字可能會從現在開始上升，我們也期待這一點。最終，我們將繼續追蹤這一情況。目前還處於發布的早期階段，我們確實希望在未來的某個時候報告該指標。

And then in terms of maintenance, I think your last question, patients are coming back on maintenance. We know that and we reported that based on the earliest patients, earliest cohort of patients that we've seen. About 1/3 of the patients have already come back. Again, early days of launch, that's a very good indicator.

然後就維護而言，我想你的最後一個問題是，病人正在重新接受維護。我們知道這一點，並且我們根據我們見過的最早的患者、最早的患者群體報告了這一點。約有三分之一的患者已經復發。再次強調，在發布的早期階段，這是一個非常好的指標。

And physicians have told us repeatedly that they expect to put the vast majority of their patients back on maintenance, and that could range anywhere 70%, 80%, 90% of the patients, assuming that they're eligible for maintenance. And so that's, I think, a goal for us, and we'll see that play out over time.

醫生們一再告訴我們，他們希望讓絕大多數患者重新接受維持治療，假設患者有資格接受維持治療，那麼這個比例可能在 70%、80% 甚至 90% 之間。所以，我認為這是我們的目標，我們會隨著時間的推移看到它的發展。

Kelly Shi, Jeffrey.

凱莉·施，傑弗裡。

So, after the second full quarter of launch, could you comment on the latest observation of treatment duration for Revuforj in real-world practice? And also, how do you expect the treatment duration to evolve over time, especially now when you have more earlier second lines of patients on the treatment?

那麼，在推出後的第二個完整季度之後，您能否評論 Revuforj 在現實世界實踐中治療持續時間的最新觀察結果？此外，您預計治療持續時間會如何隨時間變化，尤其是現在有更多早期二線患者接受治療？

Kelly, thank you for the question. So first question, duration in the real world, what are we seeing? I'm going to hand that to Steve to answer that.

凱利，謝謝你的提問。那麼第一個問題，現實世界中的持續時間，我們看到了什麼？我將把這個問題交給史蒂夫來回答。

Yes. Thanks, Kelly, for the question. And we'd always predicted this first year would be roughly in the 4 to 6-month range for average duration. Based on data that we've been able to see, we're very confident that's the case. We take a look at the earliest cohort of patients, and they're certainly within that range.

是的。謝謝凱利提出這個問題。我們一直預測第一年的平均持續時間約為 4 到 6 個月。根據我們所看到的數據，我們非常確信情況確實如此。我們觀察了最早一批患者，他們肯定處於這個範圍內。

That will improve over time. I appreciate the mention of the earlier line patients, which were also in our prepared remarks. And that's a real phenomenon. And this happened very, very quickly. The first patients at launch were not these patients. They were likely more third, fourth line patients, but it moved earlier very, very quickly, and that portends well on terms of treatment duration.

隨著時間的推移，這種情況將會改善。我很感謝你提到之前的排隊病人，我們也在準備好的發言中提到了他們。這是一個真實存在的現象。這一切發生得非常非常快。發射時的第一批病人並不是這些病人。他們很可能是第三、四線患者，但進展非常非常快，這預示著治療持續時間良好。

So a better chance of success of getting to a transplant and more likely, as Michael just described on the previous question, the concept of returning to drug. So that will build over the course of this year. We would expect in 2026 that, that average treatment duration will be six to 12 months and could skew towards the latter end of that as the launch matures and we're able to move patients earlier and physicians gain more experience.

因此，獲得移植成功的機會更大，而且正如邁克爾剛才在上一個問題中所描述的那樣，更有可能恢復用藥的概念。因此，這將在今年內逐步實現。我們預計，到 2026 年，平均治療持續時間將為 6 至 12 個月，並且隨著產品的推出、我們能夠更早地轉移患者以及醫生獲得更多經驗，治療持續時間可能會偏向後期。

Just one more question, if I may. So on the cost side, how could we expect the change quarter-over-quarter for the rest of the year?

如果可以的話，我還有一個問題。那麼在成本方面，我們如何預期今年剩餘時間的環比變化？

Thanks, Kelly. I'm going to ask Keith.

謝謝，凱利。我要去問基斯。

The cost side?

成本方面？

The cost, just change over quarter-to-quarter.

成本只是逐季度變動。

Yes. Yes. Kelly, thanks for the question. So we gave guidance today that we expect -- We changed the way we gave guidance actually. We used to give guidance with respect to OpEx inclusive of noncash stock comp, but we heard from investors that they are more focused on our cash consumption.

是的。是的。凱利，謝謝你的提問。因此，我們今天給出了我們期望的指導——我們實際上改變了給予指導的方式。我們過去常常針對包括非現金股票補償在內的營運支出提供指導，但我們從投資者那裡聽說，他們更關注我們的現金消耗。

So today, we changed the way we gave guidance to focus on our operating expenses less noncash stock comp. We said that for the third quarter, we expected that to be $95 million to $100 million and reiterated our full year guidance that we expect that to be now $370 million to $390 million.

因此，今天我們改變了指導方式，將重點放在營運費用減去非現金股票補償。我們表示，我們預計第三季的營收將達到 9,500 萬至 1 億美元，並重申了全年預期，預計營收將達到 3.7 億至 3.9 億美元。

We implicitly gave fourth quarter guidance because we have three quarters of -- two quarters of expenses, gave third quarter guidance. So the fourth quarter guidance that is implicit through the math is almost exactly even with our third quarter guidance for our research and development plus selling, general and administrative expenses less noncash stock comp.

我們隱性地給出了第四季度的指導，因為我們有三個季度——兩個季度的支出，給出了第三季度的指導。因此，透過數學隱含的第四季指引幾乎與我們第三季研發加上銷售、一般和行政費用減去非現金股票補償的指引完全一致。

Thanks very much. Congrats on the quarter, great quarter.

非常感謝。恭喜本季度，這是一個很棒的季度。

Thanks, Kelly.

謝謝，凱利。

Philip Nadeau, TD Cowen.

菲利普·納多 (Philip Nadeau)，TD Cowen。

Good afternoon. Congrats on the two successful launches. A couple of questions from us. First, on the KMT2A launch for Revuforj. You suggested, I think that 25% of patients with KMT2A for one year have initiated therapy in the second quarter, which suggests in the incident population the penetration is probably quite high.

午安.祝賀兩次發射成功。我們有幾個問題。首先，關於 Revuforj 的 KMT2A 發射。您說，我認為患有 KMT2A 一年的患者中有 25% 在第二季度開始接受治療，這表明在發病人群中滲透率可能相當高。

Can you give us a sense of where you think the penetration is in the incident KMT2A population here today in Q2 of 2025? And kind of where could that go at peak? I guess we're trying to understand how much growth could be left over the next couple of quarters before the label expansion? And then second, on the NPM1 label expansion, any update on inclusion of NPM1 in the NCCN guidelines?

您能否告訴我們，您認為 2025 年第二季 KMT2A 事件人口的滲透率是多少？那麼在巔峰時期它會去哪裡呢？我想我們想了解在標籤擴展之前接下來的幾個季度還能剩下多少成長？其次，關於 NPM1 標籤擴展，是否有關於將 NPM1 納入 NCCN 指南的最新消息？

Yes, Phil, thanks for the questions. The first question related to KMT2A and penetration in '25. I think we're going to clarify that. I'm going to ask Steve to clarify that a little bit.

是的，菲爾，謝謝你的提問。第一個問題與 KMT2A 和 25 年的滲透有關。我想我們要澄清這一點。我要請史蒂夫稍微澄清一下這一點。

Yes. Phil, thanks for the question. And, yes, I mean, so we've treated over 500 patients since launch. We often measure ourselves versus that overall available market of 2,000 KMT2A relapsed/refractory AML and ALL patients. So since launch, we estimated we've covered about 25% of that population.

是的。菲爾，謝謝你的提問。是的，自推出以來我們已經治療了 500 多名患者。我們經常將自己與 2,000 名 KMT2A 復發/難治性 AML 和 ALL 患者的整體可用市場進行比較。自推出以來，我們估計已經涵蓋了約 25% 的人口。

I think one thing to think about, it's 2,000 patients over the course of the year, not at any one point in time. There's going to be some variability as those patients are identified and diagnosed. We feel great about finding patients. Rev is very early to become the standard of care. Physicians are -- diagnostic testing is prevalent, so they're finding patients.

我認為有一件事需要考慮，那就是一年中有 2,000 名患者，而不是在任何一個時間點。在對這些患者進行識別和診斷時，會出現一些變化。我們很高興找到了病人。Rev 很早就成為了護理的標準。醫生－診斷測試很普遍，所以他們正在尋找病人。

And the -- over the course of the quarter, the number of new patients coming in has been strong and robust. So we expect that to continue for the rest of this year. We'd expect to finish the year roughly at 50% of the identified population. We think that would be a great launch, doing a lot of good for patients, but also really filling the funnel for Revuforj in our initial indication.

並且，在本季度，新入院患者的數量一直強勁增長。因此我們預計這種情況將在今年剩餘時間內持續下去。我們預計今年年底的人口數量將達到已確定人口數量的 50% 左右。我們認為這將是一次偉大的發布，不僅能為患者帶來許多好處，還能真正填補 Revuforj 在我們最初適應症中的空缺。

And then in terms of your second question, Phil, about label expansion NPM1, you had asked about the guidelines. Comment is, we've submitted to the guidelines. We published in Blood. The data is available, very helpful to our medical team to help educate in advance of launch.

然後關於你的第二個問題，Phil，關於標籤擴展 NPM1，你詢問了指導方針。評論是，我們已經提交了指南。我們在《Blood》發表過文章。這些數據是可用的，這對我們的醫療團隊在發射前進行教育非常有幫助。

Guidelines, we don't have perfect information about when the guidelines will be updated. It could be any day. We do expect it before we get approval in NPM1, and that will help aid our launch even more by having guidelines. I think that's important for payers as well as physicians. So looking forward to that, but everything is all set up and ready for launch. We're just -- we're eager to continue to make progress.

指南，我們並沒有關於何時更新指南的完整資訊。任何一天都有可能。我們確實希望在獲得 NPM1 批准之前做到這一點，並且透過提供指導方針，這將為我們的發布提供更多幫助。我認為這對付款人和醫生都很重要。所以我非常期待這一點，但一切都已準備就緒，可以發布了。我們只是──我們渴望繼續進步。

Great. Can I just follow up on the first one? So with the 2,000 patients in the year, it's reasonable to assume 1,000 patients in six months. It's been six months since launch; 500 patients have started therapy. So that's 50%. You're suggesting 50% of the identified population by the end of the year.

偉大的。我可以跟進第一個嗎？因此，如果一年中有 2,000 名患者，那麼可以合理地假設六個月內會有 1,000 名患者。該療法推出至今已有六個月，500名患者開始接受治療。所以是 50%。您建議在今年年底將確定的人口比例提高到 50%。

Obviously, more and more patients will go on over time, but this is a very sick population, so some are going to fall off. So are you kind of at peak penetration now and therefore, revenue growth over -- in the KMT2A population specifically, revenue growth over the next six to 12 months will be basically dependent on patients living longer and the duration of therapy increasing?

顯然，隨著時間的推移，會有越來越多的病人住院，但這是一個病情非常嚴重的群體，所以有些人會離開。那麼，您現在是否處於滲透率的峰值？因此，收入成長－特別是在 KMT2A 族群中，未來 6 到 12 個月的收入成長將主要取決於患者壽命的延長和治療時間的增加？

No, Phil, there's a lot of upside. So what we're seeing is over the first year, there's 2,000 eligible patients, we're going to get to 1,000 of them over the year, right, through the end of '25. We can go higher than that. So there is definitely some upside. I'd say we're not at peak penetration right now.

不，菲爾，還有很多好處。因此，我們看到第一年​​有 2,000 名符合條件的患者，到 25 年底，我們將在全年將其中的人數增加到 1,000 名。我們可以走得更高。因此肯定存在一些好處。我想說我們目前還沒有達到滲透率的峰值。

There are more patients that will ultimately be diagnosed. We have a great deal of momentum executing at a very high level. But there's a lot of upside still on KMT2Ar. And then the next driver of growth on top of that is going to be NPM1, right, which PDUFA date in late October, and that will be the next leg of the stool. And that's obviously a much larger patient population. But that's how I think about growth on the new patient side.

最終會有更多患者得到診斷。我們在執行方面擁有很大的動力，並且水準很高。但 KMT2Ar 仍有許多優勢。然後，下一個成長動力將是 NPM1，對的，PDUFA 的日期是 10 月下旬，這將是下一個支柱。顯然，這是一個更大的患者群體。但這就是我對新患者成長的看法。

Yes. And I would just add, Phil, obviously, other part of this is duration, as you brought up. The duration of therapy is going to be a key driver for KMT2A. As you treat patients earlier, more patients are going to transplant. We're seeing that evidence in our commercial experience and you're going to be able to put more patients back on therapy, we're seeing that early evidence as well.

是的。我想補充一點，菲爾，顯然，正如你提到的，這其中的另一部分是持續時間。治療持續時間將成為 KMT2A 的關鍵驅動因素。隨著您更早治療患者，將會有更多的患者接受移植。我們在商業經驗中看到了這項證據，你將能夠讓更多的病人重新接受治療，我們也看到了這個早期證據。

So we expect those to be major drivers year-over-year as you've added -- you're adding new patients, so the new patient starts plus the compounding effect of duration of therapy for these patients who come back and stay on maintenance. So, I think there's quite a bit of growth left to do.

因此，我們預計這些將成為逐年增長的主要驅動力，因為您正在增加新患者，因此新患者的開始加上這些回來並保持維持治療的患者的治療持續時間的複合效應。所以，我認為還有很大的發展空間。

Peter Lawson, Barclays Bank

彼得·勞森，巴克萊銀行

Thank you so much. Congratulations on the quarter. Just as we think about the looming FDA approval, what can you tell us around any remaining open items or feedback you've got from the FDA and anything that kind of helps add around the confidence around the FDA approval?

太感謝了。恭喜本季。就在我們考慮即將到來的 FDA 批准時，您能否告訴我們有關任何剩餘未決事項或您從 FDA 獲得的反饋以及任何有助於增加對 FDA 批准的信心的事情？

Yes, Phil. Sorry, Peter, thank you for the questions. First, on FDA approval, I'm going to turn it over to Nick. Are we learning anything new?

是的，菲爾。抱歉，彼得，謝謝你的提問。首先，關於 FDA 批准，我將把它交給尼克。我們學到了什麼新東西嗎？

Yes. Thank you. The submission is progressing very well. We have our PDUFA date. We've been working very closely with the FDA. And so it's a team we know well now, and things are progressing very well according to plan. So we're looking forward to the PDUFA as guided on October 25th.

是的。謝謝。提交工作進展非常順利。我們有 PDUFA 日期。我們一直與 FDA 密切合作。所以我們現在非常了解這個團隊，而且事情正在按照計劃順利進行。因此，我們期待 10 月 25 日的 PDUFA 指導。

Yes. And with regard to your second question, maintenance, what percentage do we think we can put back on? Look, I think we had heard from physicians, we continue to hear from physicians, the vast majority, if not all of their patients, they'd like to put back on maintenance. We know that not every patient will be eligible for maintenance.

是的。關於您的第二個問題，維護費用，我們認為可以節省多少百分比？聽著，我想我們已經聽取了醫生的意見，我們也繼續聽取醫生的意見，絕大多數（如果不是全部）患者都希望重新接受維持治療。我們知道並非每位患者都有資格獲得維持治療。

But with physicians treating patients earlier and the majority of the treatment being concentrated in second line, even at this early stage of launch, that's a very good sign that physicians will drive hard to take more patients to transplant, which give us more opportunity to put them back on once they clear their transplant and graft. So, I can't give you an exact percentage, but it should be a very high percentage of KMT2A patients.

但是，由於醫生更早地對患者進行治療，並且大多數治療集中在二線，即使在啟動的早期階段，這也是一個非常好的跡象，表明醫生將努力讓更多的患者接受移植，這為我們提供了更多機會，一旦他們的移植和移植物清除乾淨，就可以讓他們重新接受治療。所以，我無法給你一個確切的百分比，但 KMT2A 患者的比例應該非常高。

Maybe I could circle back on the first question just around the FDA. I know there's always a level of uncertainty, and it seems to be a heightened level of uncertainty. Have you seen any changes in that dialogue, any moving targets?

也許我可以回到第一個有關 FDA 的問題。我知道總是存在著一定程度的不確定性，而且這種不確定性似乎加劇。您是否發現對話中存在任何變化，目標有任何變化？

Yes Peter, no. I mean I think that's clearly, that's not there's nothing to indicate that it's anything other than really very good progress. We have priority review. We're under our tour. We're having consistent quality dialogue with the agency. The feedback has been very good. We have a PDUFA date that's coming close, and we're prepared for launch. So I think everything on the regulatory front is really hitting on all cylinders.

是的，彼得，不。我的意思是，我認為這顯然沒有任何跡象表明它取得了非常好的進展。我們有優先審查權。我們正在進行巡迴演出。我們正在與該機構進行持續的品質對話。反饋非常好。我們的 PDUFA 日期即將到來，我們已做好發布準備。所以我認為監管方面的一切都在全力進行。

Perfect. Thank you so much. Thanks.

完美的。太感謝了。謝謝。

Paul Jeng, Guggenheim Securities

Paul Jeng，古根漢證券

This is Paul on for Michael. I have two on the frontline combo opportunities. So first on the recent EHA updates from BEAT AML. It seems pretty clear that revumenib is enhancing the CR and MRD compared to ven/aza alone. But would love to get your thoughts on the degree of OS improvement you're seeing and whether or not you plan to provide another survival update in the study with additional follow-up?

這是保羅代替麥可上場。我有兩次前線組合機會。首先介紹一下 BEAT AML 最近發布的 EHA 更新。很明顯，與單獨使用 ven/aza 相比，revumenib 可以提高 CR 和 MRD。但是，我很想聽聽您對所看到的 OS 改善程度的看法，以及您是否計劃在研究中提供另一個生存更新並進行額外的跟進？

And then secondly, just looking ahead to the intensive chemo combo, can you sort of talk about how we should think about key CR and MRD benchmarks for that combo and sort of what to expect for the update later this year?

其次，展望強化化療組合，您能否談談我們應該如何看待該組合的關鍵 CR 和 MRD 基準，以及今年稍後的更新有何期待？

Paul, thank you so much for the questions. I'm going to turn it over to Nick to touch on the BEAT AML piece of this first

保羅，非常感謝你的提問。我將首先讓 Nick 談談 BEAT AML 部分

Yes. Thank you for that. And firstly, very encouraged by the BEAT AML study. I mean, this was an important study. We were able to confirm a dose to take into Phase III and show that the dose was tolerable, and also, as you say, report out some early efficacy measures. And I think the efficacy measures that are probably most in this most important in this setting are the complete response rate and MRD negativity because remember, this is a relatively small 43-patient Phase Ib study.

是的。謝謝你。首先，BEAT AML 研究讓我深受鼓舞。我的意思是，這是一項重要的研究。我們能夠確認進入第三階段的劑量，並表明該劑量是可以耐受的，而且，正如您所說，報告了一些早期的功效測量結果。我認為在這種情況下最重要的療效指標可能是完全緩解率和 MRD 陰性，因為請記住，這是一項相對較小的 43 名患者的 Ib 期研究。

So interpretation in that context is quite difficult. And the CR rate and MRD negativity were very high. They were 67% and 100% MRD negativity, which, as I said in the earlier comments, are really a step change above what you expect from historical controls. Now, when you look at the overall survival, you have to remember that the median follow-up is quite short currently.

因此，在這種背景下進行解釋是相當困難的。且 CR 率和 MRD 陰性率非常高。它們的 MRD 陰性率為 67% 和 100%，正如我在先前的評論中所說，這確實比你對歷史對照的預期有了很大的變化。現在，當您查看整體存活率時，您必須記住，目前的中位數追蹤時間相當短。

The median follow-up was only around seven months, and it's over 20 months in VIALE-A. So certainly, we expect as those data mature, you'll see some changes in the median OS. There's a lot of steps in the Kaplan-Meier currently, which suggests the median is quite unstable and it's therefore very difficult to estimate.

中位追蹤時間僅 7 個月左右，而 VIALE-A 的追蹤時間超過 20 個月。因此，我們當然預計，隨著這些數據的成熟，您會看到中位數 OS 的一些變化。目前，Kaplan-Meier 中有很多步驟，這表明中位數非常不穩定，因此很難估計。

Having said that, it's already very comparable or somewhat similar to VIALE-A, which you must also recall is a very heterogeneous group of subtypes of AML with a variety of different genetic mutations. And when you actually benchmark against NPM1, you probably find the median overall survival is a little less than was reported and closer to 10 months.

話雖如此，它已經與 VIALE-A 非常相似或有些相似，您還必須記住，它是一組非常異質的 AML 亞型，具有多種不同的基因突變。當您實際以 NPM1 為基準時，您可能會發現中位總體生存期比報告的要短一些，接近 10 個月。

So, in summary, we remain extremely confident in the profile of the combination with ven/aza. And I think it gives us a very high level of confidence that the EVOLVE-2 study that we're doing in collaboration with HOVON will read out well in due course. With regard the intensive chemotherapy and the MRD negative CR, we think both CR for unfit and MRD negative CR, both plasma and bone marrow are important endpoints in this setting.

因此，總而言之，我們對 ven/aza 的組合效果仍然非常有信心。我認為這讓我們非常有信心，我們與 HOVON 合作進行的 EVOLVE-2 研究將在適當的時候取得良好結果。關於強化化療和 MRD 陰性 CR，我們認為不適合的 CR 和 MRD 陰性 CR、血漿和骨髓都是這種情況下的重要終點。

They've been shown to predict for improved outcomes around event-free survival and OS and believe that they could serve as surrogates to support accelerated approval. Those are obviously discussions we have had with the agency and have refined those. They are built into the protocols as dual primary endpoints, which means that they are independently powered.

事實證明，它們可以預測無事件生存期和 OS 的改善結果，並相信它們可以作為支持加速批准的替代品。這些顯然是我們與該機構進行的討論，並且已經進行了改進。它們作為雙主端點內建於協定中，這意味著它們獨立供電。

So you could have either the surrogate CR endpoint or the time-to-event endpoint, whether that be OS or EF, to give a positive study. And we remain quite confident that both of those should read out favorably. As previously indicated, we will be updating data for our combination with intensive chemotherapy for fit patients, specifically the 7+3 regimen from our own sponsored study, the 708 study.

因此，您可以使用替代 CR 終點或事件發生時間終點（無論是 OS 還是 EF）來進行積極的研究。我們仍然非常有信心，這兩項結果都會是有利的。如前所述，我們將更新適合患者的強化化療組合療法的數據，特別是我們自己贊助的研究 708 研究中採用的 ​​7+3 療法。

And also, we'll likely hear from the study we're doing in collaboration with the NCI, which is also a combination of intensive chemotherapy in the latter part of this year. And those data should both confirm the dose, tolerability, and also early signs of efficacy to support our Phase IIIs with intensive chemotherapy. So overall, we feel very confident about the programs, and we really have very good momentum going into the latter part of this year.

此外，我們可能會聽到我們與 NCI 合作進行的研究的消息，這也是今年下半年強化化療的組合。這些數據應該能夠證實劑量、耐受性以及療效的早期跡象，從而支持我們進行強化化療的 III 期臨床研究。所以總的來說，我們對這些項目非常有信心，而且我們在今年下半年確實有著非常好的發展勢頭。

Thank you, Paul. Thank you.

謝謝你，保羅。謝謝。

Yigal Nochomovitz, Citigroup Inc.

花旗集團的 Yigal Nochomovitz

Hey, Michael and team, thank you. On the 1/3 of the patients that have restarted after the transplant and then the 2/3 that don't, could you just clarify, so of those 2/3, are they not expected to restart? Or is it simply that they're not ready to restart and the expectation is that most of them, in fact, will restart?

嘿，麥可和他的團隊，謝謝你們。關於移植後重新開始的 1/3 例患者和沒有重新開始的 2/3 例患者，您能否澄清一下，那麼在這 2/3 例患者中，他們是否預計不會重新開始？或者只是因為他們還沒有準備好重啟，而人們期望他們中的大多數實際上都會重啟？

Yigal, thanks for the questions. It's the latter, right? So, clearly, we said early days, 1/3 have restarted already, which is very encouraging to us, which does leave 2/3 of those patients who could restart. And we expect a very high proportion of patients to restart out of that cohort as well.

Yigal，謝謝你的提問。是後者吧？因此，顯然，我們說早期，1/3 的患者已經重新開始治療，這對我們來說非常令人鼓舞，其中 2/3 的患者可以重新開始治療。我們預計很大比例的患者也會從該群體中重新開始治療。

So it's an ongoing, evolving landscape of patients coming back from transplant and going on to maintenance. So we haven't excluded that 2/3. We actually -- we're waiting for those to come back.

因此，患者從移植手術中恢復並繼續接受維持治療是一個持續不斷、不斷發展的過程。所以我們並沒有排除那 2/3。我們實際上——我們正在等待它們回來。

Okay. And then just can you clarify on the mechanics? Do they need to get a reimbursement approval again when they come back after the transplant? Or is it seamless and they just start Revuforj again without a second need to request the reimbursement?

好的。那你能解釋一下其中的機制嗎？移植後回來時他們是否需要再次獲得報銷批准？或者它是無縫的，他們只需再次啟動 Revuforj 而不需要再次請求報銷？

Steve, do you want to address that?

史蒂夫，你想解決這個問題嗎？

Yes. Our expectation, Yigal, it's pretty seamless. I mean, in this industry, I mean, it's six-month renewals, which are pretty standard. That may be the case here. But typically, if you're within that window, they'll restart without any challenges from payers.

是的。我們的期望，Yigal，它是相當無縫的。我的意思是，在這個行業中，六個月的續約是相當標準的。這裡的情況可能就是這樣。但通常情況下，如果您處於該時間段內，他們將重新啟動，而不會受到付款人的任何挑戰。

And even when there is a restart or a reinitiation of a prescription, we have not heard of any challenges with doing that. Payers covered the formulary coverages over 97%. Claims are being reimbursed on a regular basis. So we're not expecting any challenges with restarting at all.

即使重新開始或重新啟動處方，我們也沒聽說這樣做有什麼困難。付款人涵蓋了 97% 以上的處方覆蓋範圍。索賠將定期償還。所以我們預計重啟不會遇到任何挑戰。

Okay. And then lastly, I'm just curious if you could speak in a little more detail about this first wave of the real-world evidence that you're going to have at the end of the year? Can you just expand on that a little, please?

好的。最後，我很好奇，您是否可以更詳細地談談您將在今年年底獲得的第一波現實世界證據？能稍微詳細說明一下嗎？

Maybe Nick can take that.

也許尼克可以接受這一點。

Yes, I'd be happy to. So we're obviously working with leading centers across the US and leading thought leaders, and we're at the point now with the drug being used in clinic from commercial supply that we're getting some interesting series of data from physicians' experience in the real world. So we're collaborating closely with them to collect those data and look forward to presenting those real-world experiences from those centers in the latter part of this year.

是的，我很樂意。因此，我們顯然正在與美國各地的領先中心和領先的思想領袖合作，現在我們正處於從商業供應中用於臨床的藥物階段，我們從醫生在現實世界中的經驗中獲得了一些有趣的數據。因此，我們正在與他們密切合作，收集這些數據，並期待在今年下半年展示這些中心的真實經驗。

And I think we're uniquely well placed to be able to do that with this new therapeutic classes. We're now available commercially in the clinic and can actually report real-world experience versus just clinical trial experience. So I think those data and how the drug is getting used in the real world will be very insightful, and we're looking forward to those reporting out later in the year.

我認為，我們擁有獨特的優勢，能夠透過這種新的治療課程來實現這一目標。我們現在可以在臨床上進行商業化應用，並且可以實際報告現實世界的經驗，而不僅僅是臨床試驗經驗。因此我認為這些數據以及該藥物在現實世界中的使用將非常具有啟發性，我們期待今年稍後發布這些報告。

Thanks.

謝謝。

Thank you, Yu.

謝謝你，Yu。

Justin Zelin, BTIG

BTIG 的 Justin Zelin

Congrats on the strong quarter. So looking ahead to the October 25th PDUFA date for NPM1 label expansion, could you walk us through how you're preparing the commercial organization for launch readiness? And do you anticipate a meaningful incremental uptake in the population out of the gate or would it be more gradual?

恭喜本季業績強勁。那麼展望 10 月 25 日 PDUFA 日期的 NPM1 標籤擴展，您能否向我們介紹您如何為商業組織做好發布準備？您是否預期人口的成長會有一個有意義的增量，還是會是一個漸進的過程？

Yes. Thanks, Justin, for the questions. I'm going to turn it over to Steve to touch on the launch readiness, launch maintenance.

是的。謝謝賈斯汀提出的問題。我將把話題交給史蒂夫，讓他談談發射準備和發射維護。

Yes. So we're in market, Justin. I appreciate, obviously, with another indication, which would be different from someone who's entering the market. So here's how I would think about this launch. I mean part of the success or the preparation is doing a great job right now, right?

是的。所以我們在市場上，賈斯汀。顯然，我很欣賞另一個跡象，這與進入市場的人有所不同。以下是我對這次發布的看法。我的意思是成功的一部分或準備就是現在做得很好，對嗎？

So physicians, we're leveraging that market experience in KMT2Ar. Patients understand how to dose the drug. They appreciate the dosing options that they have, how do they initiate treatment, how to manage any AEs that might occur in treatment initiation, getting through them, what do they expect from efficacy and how to bring the drug in, right, how do they -- as a treatment center prefer to bring the drug in.

因此，醫生們，我們正在利用 KMT2Ar 的市場經驗。患者了解如何服用藥物。他們欣賞他們所擁有的劑量選擇，他們如何開始治療，如何處理治療開始時可能發生的任何不良反應，如何度過這些不良反應，他們對療效有何期望，如何引入藥物，對，他們——作為治療中心更喜歡如何引入藥物。

So that's one piece. I think the other piece is we're in the same audience, right, right now. So when we think about treatment centers that treat KMT2Ar, they are the same ones that treat NPM1. So we're already there. We've got a best-in-class customer-facing team. They have excellent relationships. They understand the space. They understand how these treatment centers treat. So they've already got a leg up at once the indication is granted on the sNDA.

這就是其中一件事。我認為另一點是我們現在是同一個觀眾群。因此，當我們想到治療 KMT2Ar 的治療中心時，它們與治療 NPM1 的治療中心是相同的。所以我們已經到了那裡。我們擁有一流的客戶服務團隊。他們的關係非常好。他們了解這個空間。他們了解這些治療中心如何治療。因此，一旦 sNDA 批准該適應症，他們就已經佔據了優勢。

And the last piece is just a great drug, right? We believe we've got a best-in-class profile with NPM1 data. Any physician would tell you most important across any of these types of agents is does the drug work, and does it work better than anything else that's out there? We believe we've got a winner in Revuforj.

最後一塊只是一劑良藥，對吧？我們相信，我們已擁有一流的 NPM1 資料資料。任何醫生都會告訴你，對於這些類型的藥物來說，最重要的是藥物是否有效，以及它是否比其他藥物更有效？我們相信 Revuforj 是我們的贏家。

The efficacy data really screams; physicians tell us that. I think as Michael may have pointed out in his comments, the fact that we've got multiple indications for menin inhibitor, that is a big deal. That is not something that's minor. And that holds for treaters. It also holds for payers, right? Payers when looking at a second indication, like they are with Revuforj, it's an easy add and that will get us ahead. So those are the things I think about.

療效數據確實令人震驚；醫生告訴我們這一點。我認為，正如邁克爾在他的評論中指出的那樣，我們已經獲得了多種腦膜抑制劑的適應症，這是一件大事。這不是一件小事。這對於治療者來說也是如此。這對付款人來說也同樣適用，對嗎？當付款人看到第二個適應症時，就像他們看到 Revuforj 一樣，這是一個簡單的添加，這將使我們領先。這些就是我所考慮的事情。

In terms of uptake, absolutely, we're expecting a bump, right? We know that right now the usage outside of KMT2Ar is small. We maintain -- it's about 10%. We'll call it spontaneous or off-label use. The biggest bang for NPM1 is going to be at the indication granting, right? When promotionally and commercially we can stand behind the drug, we think it will make a big splash. Physicians are ready for it.

就吸收量而言，我們絕對期待出現成長，對嗎？我們知道，目前 KMT2Ar 以外的使用量很小。我們維持——大約是 10%。我們稱之為自發性使用或標籤外使用。NPM1 的最大亮點在於指示授予，對嗎？當我們能夠在宣傳和商業上支持這種藥物時，我們認為它會引起巨大的轟動。醫生們已經做好準備了。

So we'll expect a decent driver at that time later this year. Yes. I'll just add that adding NPM1, you take your patient population from about 2,000 patients to 6,000 patients, that's a big difference. And so we expect it to be a really important driver, not only starting at the end of the year, but going into next year and beyond. It's important to be first. It's important to have the best profile. We have both. So we're in good shape.

因此我們期待今年稍後會出現一位優秀的車手。是的。我只想補充一點，在添加 NPM1 後，您的患者數量將從大約 2,000 名患者增加到 6,000 名患者，這是一個很大的差異。因此，我們預計它將成為一個非常重要的驅動力，不僅從今年年底開始，而且會持續到明年及以後。成為第一名很重要。擁有最好的個人資料非常重要。我們兩者都有。所以我們的狀態很好。

Yeah, I just add that adding MPM1, you take your patient population of about 2000 patients to 6,000 patients, that's a big difference. And so we expect it to be a really important driver not only starting at the end of the year, but going to next year and beyond. It's, important to be first. It's important to have the best profile. We have both, so we're in good shape.

是的，我補充一下，加上MPM1，你的患者數量會從大約2000人增加到6000人，這是一個很大的變化。因此，我們預計它不僅會在今年年底開始，而且會持續到明年及以後，成為一個非常重要的驅動力。成為第一家公司非常重要，擁有最佳的形像也非常重要。我們兩者兼有，所以我們的狀態很好。

Great, thanks for taking the questions. Thanks.

太好了，感謝您回答這些問題。謝謝。

Salim Syed, Mizuho Securities USA

薩利姆‧賽義德，瑞穗證券美國公司

Congrats on the quarter. Mike, Keith, maybe just a couple from us. One on Niktimvo. So -- and I apologize, this is going to be another math question. But when I look at 2026, consensus currently, I think, is around $240 million or so on the end user sales number. And just kind of like looking at some of the numbers that have been released between yourselves and Incyte, there were $45 million of sales, I think, or so ex inventory, that's our number, I think, 4,500 infusions.

恭喜本季取得佳績。麥克、基思，也許只是我們的一對夫婦。一個在 Niktimvo。所以——很抱歉，這又是一個數學問題。但當我展望 2026 年時，我認為目前的共識是最終用戶銷售額約 2.4 億美元左右。就像查看你們和 Incyte 之間發布的一些數據一樣，我認為銷售額約為 4500 萬美元，或者不含庫存，這是我們的數字，我認為是 4,500 次輸液。

I think they mentioned that on their call. I know you guys are saying over 4,000, but they said 4,500. So it looks at about $10,000 net price per infusion, assuming the trial duration of 10.3 months. You start to get to this price of $225,000 for the 22 infusions that would take place, so assuming they talked about having 1,000 patients at the end of this year, perhaps.

我想他們在電話裡提到了這一點。我知道你們說的是超過 4,000，但他們說的是 4,500。因此，假設試驗期為 10.3 個月，則每次輸液的淨價約為 10,000 美元。22 次輸液的費用為 225,000 美元，因此假設他們談到今年年底將有 1,000 名患者，也許吧。

So you start to get to these numbers of $225,000. And again, that's using the 10.3, not the 12-month duration, no additional inventory impact, no additional penetration, no growth. Is it just me? Or is that number just incredibly light, the [26] Niktimvo end-user sales number just based on that math? Is there something I'm missing?

因此，您開始得到 225,000 美元這個數字。再次強調，這是使用 10.3，而不是 12 個月的持續時間，沒有額外的庫存影響，沒有額外的滲透，沒有增長。只有我一個人這樣嗎？或者這個數字只是難以置信的輕，[26] Niktimvo 最終用戶銷售數字只是基於這個計算？我遺漏了什麼嗎？

Thanks for the question, Salim. So we're trying to track with your math here. But Keith, why don't you comment?

謝謝你的提問，薩利姆。因此我們嘗試在這裡追蹤你的數學。但是基思，為什麼不發表評論呢？

Yes. Trying to track your math. I mean, I think going back to some of the comments that Mohammed and Bill made on the call that Incyte had last week, I think they were asked a question about peak sales, and there was a response that included an estimate of looking at the REZUROCK launch and comparing the Niktimvo launch to that launch.

是的。試著追蹤你的數學。我的意思是，我想回顧一下穆罕默德和比爾在上週 Incyte 電話會議上發表的一些評論，我認為他們被問及一個關於峰值銷售的問題，而他們的回答包括對 REZUROCK 發布情況的估計，並將 Niktimvo 發布情況與該發布情況進行比較。

We -- I think we and Incyte both think that that could be a low watermark for us. And if you just look forward, Michael made comments in his prepared remarks that third full year of launch, Niktimvo's annualizing over $500 million US only. Again, we think looking forward to 2028, when we'll still only have a relapsed/refractory, we don't expect to have necessarily frontline indications by then. But we definitely think this can be several $100 million product in the next few years.

我們——我認為我們和 Incyte 都認為這對我們來說可能是一個低水位線。如果你只是向前看，邁克爾在他準備好的演講中表示，在推出後的第三年，Niktimvo 的年收入將超過 5 億美元。再次，我們認為展望 2028 年，那時我們仍然只會遇到復發/難治性病例，我們預計到那時不一定會有前線適應症。但我們確實認為，在未來幾年內，這可以成為價值數億美元的產品。

Okay. Yes. I mean they did talk about the [$1,000 million] sort of at the end of the year from the current [$700 million] or so. That's sort of the basis for the math. But I understand your point. And just quickly, I guess, on your slides, it looks like you updated your EPi data for the NPM1 from 3,000 to 4,500 just to 4,500. Is there something you guys did on the Epi to make you more confident around the upper end of that range? The one that's $5 billion TAM?

好的。是的。我的意思是，他們確實談到了從目前的 [7 億美元] 左右到年底 [10 億美元] 左右。這就是數學的基礎。但我明白你的意思。我想，在您的投影片上，您似乎已經將 NPM1 的 EPi 資料從 3,000 更新到了 4,500，只是 4,500。你們對 Epi 做了什麼來讓你們對該範圍的上限更有信心嗎？那個總資產規模是 50 億美元的？

Yes. So thanks for the question. Look, the only thing that a lot of things give us confidence. I think when we think about the EPi, I mean, we're treating patients now really much more in the second line. So you're going to capture the upper end of that number if you continue to treat in that capacity.

是的。感謝您的提問。瞧，很多事情都給我們信心。我認為，當我們考慮 EPi 時，我的意思是，我們現在實際上更多地在第二線治療患者。因此，如果您繼續以這種身份進行治療，您將獲得該數字的上限。

So that's how physicians tell us they want to treat. They want to treat earlier. And so that gives us confidence to kind of capture the upper end of that range. Just making a comment, I want to go back for a second to your Niktimvo question. You mentioned duration at 10 months. I would just point to the fact that this is a drug that physicians intend to keep patients on potentially for years. I mean this is a very efficacious drug.

這就是醫生告訴我們他們想要治療的方式。他們想早點治療。因此，這給了我們信心去達到該範圍的上限。只是發表一下評論，我想稍微回顧一下您關於 Niktimvo 的問題。您提到持續時間為 10 個月。我只想指出，醫生希望病人服用這種藥物多年。我的意思是這是一種非常有效的藥物。

And so, we believe that there's potentially a lot of upside in duration of therapy. And so I would be thinking about your assumptions there, and we'll track with that, obviously, over time. But I think that's a -- one thing that stood out to me in your math that you might want to take a look at.

因此，我們相信延長治療時間可能會帶來很大的好處。因此，我會考慮你的假設，並且顯然，我們會隨著時間的推移進行追蹤。但我認為，這是你的數學中讓我印象深刻的一件事，你可能需要看一下。

Yeah, it was meant to be conservative.

是的，它本來是保守的。

Yes. No, I think as a conservative estimate, I understand where you're coming from, but I think we are encouraged by duration here and what this category and what specifically this drug and mechanism can bear. So I would just pay attention.

是的。不，我認為作為保守估計，我理解你的意思，但我認為我們對這裡的持續時間以及這個類別以及這種藥物和機制所能承受的具體影響感到鼓舞。所以我只需要注意。

Especially five months into launch, Incyte made comments that 80% to 90% of patients that started on therapy are still on therapy.

特別是在推出該藥物五個月後，Incyte 表示，80% 至 90% 開始接受治療的患者仍在接受治療。

Very good point. Yeah, fair enough. Thanks, so much guys, appreciate it.

非常好的觀點。是的，很公平。非常感謝大家，感激不盡。

Thanks Salim.

謝謝薩利姆。

David Dai, UBS.

戴維戴，瑞銀。

Congrats on the quarter. A couple for me. One, just on the $28 million of Revuforj revenue, could you talk about the percentage of revenue is inventory? And also, how much of that is coming from new patient start versus refill?

恭喜本季取得佳績。對我來說是一對。首先，就 Revuforj 的 2800 萬美元收入而言，您能談談庫存佔收入的百分比嗎？此外，其中有多少是來自新病人的治療，有多少是來自重新治療的病人？

Thanks, David.

謝謝，大衛。

Yes. So David made comments that said that well, I'm sorry, let me back up. The demand in the quarter was driven by patient growth, patient demand. Inventory stayed level, two to three weeks, and we expect that to be the case going forward. It's pretty typical of a drug that's used and distributed using specialty pharmacy specialty distributors, two to three weeks of inventory. So we don't expect that to grow.

是的。因此，大衛發表評論說，好吧，對不起，讓我回顧一下。本季度的需求是由患者成長和患者需求所推動的。庫存保持在兩到三週的水平，我們預計未來情況也將如此。這是非常典型的藥品，透過專業藥房專業分銷商使用和分銷，庫存量為兩到三週。所以我們預計這個數字不會成長。

Got it. Okay. And then just another question on the patients on the stem cell transplant. And right now, you have about 33%, 1/4 of it or 1/3. I'm just curious, do you expect this to increase given that you have 50% of patients currently treated in the second line? So how should we think about this going forward in terms of the increase in stem cell transplantation?.

知道了。好的。然後是關於接受幹細胞移植的患者的另一個問題。而現在，您擁有的大約是 33%、1/4 或 1/3。我只是好奇，考慮到目前有 50% 的患者接受第二線治療，您是否預計這個數字會增加？那麼，從幹細胞移植的增加的角度來看，我們應該如何看待這個問題呢？

David, thanks for the question. We tried to get at this a little earlier. Look, I think the transplant rate at 1/3 -- remember, in AUGMENT-101, we were at about 1/4 of patients going to transplant. Now we're at about 1/3. We're treating patients a lot earlier instead of third and fourth line, we're more second and third line. 70% of our prescriptions are in that second and third line.

大衛，謝謝你的提問。我們試圖儘早解決這個問題。瞧，我認為移植率為 1/3——記住，在 AUGMENT-101 中，大約有 1/4 的患者需要進行移植。現在我們大約完成了 1/3。我們對患者的治療更早，而不是三線和四線，我們更多的是二線和三線。我們 70% 的處方都是二線和三線的。

Transplant rate could go 50% higher. We don't know. But we are expecting it to materially change over time and get better. And what gives us confidence is that we know if we treat patients earlier, they tend to get to a higher level of response, higher rate of response and are more eligible or will be eligible for a transplant. So I think that's what's giving us confidence. We don't have the upper bound of that, but we do expect it to grow over time.

移植率可能會提高50%。我們不知道。但我們預計它會隨著時間的推移而發生實質變化並變得更好。讓我們充滿信心的是，我們知道如果我們更早治療患者，他們往往會獲得更高的反應水平、更高的反應率，並且更有資格或將有資格接受移植。所以我認為這就是給我們信心的原因。我們沒有這個上限，但我們確實預計它會隨著時間的推移而增長。

I think it's something in my questions.

我認為這是我的問題中涉及的內容。

Thank you, David.

謝謝你，大衛。

Jason Zemansky, Bank of America.

美國銀行的傑森·澤曼斯基。

A couple from us, if we may, based on your earlier comments. But first being, of the 2,000 or so relapsed/refractory KMT2A patients, can you give us any color on your assumptions regarding the overall peak penetration here?

如果可以的話，根據您先前的評論，我們可以提供一些建議。但首先，在約 2,000 名復發/難治性 KMT2A 患者中，您能否就此處的整體峰值滲透率的假設提供一些資訊？

And then similarly, given the comments regarding the overall opportunity in relapsed/refractory, at least as far as your cash runway goes, any color on your insights or assumptions as far as the competitive split in the NPM1 population look like?

同樣，考慮到關於復發/難治性治療的總體機會的評論，至少就您的現金流而言，您對 NPM1 人群的競爭分裂有何見解或假設？

Thanks, Jason. Thanks for the question. So first question related to peak penetration, our estimates on peak penetration for the 2,000 KMT2A patients. Steve, do you want to take a shot at that?

謝謝，傑森。謝謝你的提問。因此，第一個問題與峰值滲透率有關，我們對 2,000 名 KMT2A 患者的峰值滲透率進行了估計。史蒂夫，你想嘗試嗎？

I think we can, as we've said, we've already covered 25% of the population. We'll get to 50% of that. There's some upsides to that. We haven't guided to a number on peak, but I think, we'll be at levels at 1,000 that are close to the upper end of models that that some of you may have, but we think there's some, beyond that, tweeting earlier, I think as Michael said.

我認為我們可以，正如我們所說，我們已經涵蓋了 25% 的人口。我們將達到其中的 50%。這樣做有一些好處。我們還沒有預測峰值數字，但我認為，我們將達到 1,000 的水平，接近你們中的一些人可能擁有的模型的上限，但我們認為，除此之外還有一些，正如邁克爾之前所說的那樣。

Brings more people in and just remember Jason and everyone that in KMT2AR there's no one in the near term coming to market. So it is really white space and rev is already the standard of care after just seven months on market physicians are using it that way.

吸引更多的人加入，記住 Jason 和所有人，在 KMT2AR 中短期內沒有人進入市場。因此，這確實是一個空白領域，而且在上市僅僅七個月之後，rev 就已經成為了護理標準，醫生們就是這樣使用它的。

Yes. Jason, I would say there's penetration into a market never happens within one year. It always takes an oncology more than that. And I think we expect, as Steve said, within 1,000 patients this year. So we have more work to do next year and the year beyond. So that's, I think, just in terms of new patient starts.

是的。傑森，我想說，市場滲透從來不會在一年之內發生。這總是需要腫瘤學的幫助。正如史蒂夫所說，我認為我們預計今年的患者人數將在 1,000 人左右。因此，明年和未來我們還有更多的工作要做。所以，我認為這只是就新病人開始的數量而言。

In terms of really building this market, I'll say it again, duration of therapy is going to be key, right? Physicians treating earlier, we know that, that's going to give us the best outcomes. Patients are going back on therapy post-transplant.

就真正建立這個市場而言，我再說一遍，治療時間是關鍵，對嗎？我們知道，醫生儘早治療將為我們帶來最好的結果。患者在移植後重新接受治療。

That will ultimately compound the revenue as it goes forward, patients staying on drug for long periods of time. So, I think those are the real drivers, those two things. It's actually pretty simple. But it's not just about how many patients you can penetrate on KMT2A. It's how long they stay on drug as well. And then overall opportunity, you had mentioned the second question being, what do you -- what's your estimate for competitive split in NPM1.

隨著患者長期服用該藥物，最終將增加收入。所以，我認為這兩件事才是真正的驅動因素。事實上這很簡單。但這不僅僅是關於 KMT2A 上可以接觸多少患者。這也是他們吸毒時間長短的問題。然後是總體機會，您提到的第二個問題是，您對 NPM1 中的競爭分裂的估計是多少。

Look, I think we're first to market. We know we have best profile. I think the data speaks for itself. We're feeling very confident about that. We would expect to have a significant percentage of that market and dominating NPM1 as well as KMT2A. So we feel very positive about the fact that we're entering the market first. And that's essentially how we see it. So we're not -- we can't guide exactly to what the split would be, but we would expect to have a big share.

瞧，我認為我們是第一個進入市場的人。我們知道我們擁有最好的形象。我認為數據說明了一切。我們對此非常有信心。我們期望佔據該市場的很大份額，並主導 NPM1 和 KMT2A。因此，我們對率先進入該市場感到非常樂觀。這基本上就是我們所看到的情況。所以我們無法準確預測分成比例，但我們預期會佔很大份額。

Fair enough, appreciate the color thanks guys.

很公平，感謝大家的欣賞。

George Farmer, Scotiabank

喬治法默，加拿大豐業銀行

This is Chloe on for George. A couple from us. Can you talk a little bit about the monitoring that's happening in the real world right now for potential cardiac AEs, how they're being managed? And to the extent that you're privy to this information, what percent of these cardiac AEs, like the QT prolongation, is due to revumenib as opposed to any concomitant medications? And how many of those have resulted in discontinuations in the real world?

這是克洛伊 (Chloe) 代替喬治 (George) 上場。我們中的一對夫婦。您能否簡單談談目前現實世界中對潛在心臟不良事件的監測情況以及如何進行管理？就您所了解的資訊而言，這些心臟不良事件（如 QT 間期延長）中有多少百分比是由於瑞伐他汀引起的，而不是由任何同時服用的藥物引起的？其中有多少在現實世界中導致了停產？

Then number two, if you could give some color on how to model the royalty pharma interest expense in the P&L moving forward, that would be super helpful. And the last one on Niktimvo. In IPF, could you please speak to the unmet need, how big that opportunity is and how you're thinking about positioning in a market that's dominated currently by generics?

第二，如果您能詳細說明如何在未來的損益表中模擬特許權使用費製藥利息支出，那將非常有幫助。最後一個是關於 Niktimvo 的。在 IPF 中，您能否談談未滿足的需求、這個機會有多大以及您如何考慮在目前由仿製藥主導的市場中定位？

Chloe, thanks for your questions. So I counted three. So let's start with the first one. Nick will take that. How is monitoring being done?

克洛伊，謝謝你的提問。於是我數了三。那麼讓我們從第一個開始。尼克會接受的。監控是如何進行的？

Yes. Thank you for the question. So firstly, we've shown in our extensive clinical trial experience now that management of QT is done very simply. There's clear guidelines in the label now for QTs in the first month. We know that almost all patients that have any sign of prolongation happens early and is monitored and managed appropriately. That's very consistent with our real-world experience.

是的。謝謝你的提問。首先，我們豐富的臨床試驗經驗表明，QT 的管理非常簡單。現在標籤上對第一個月的 QT 有明確的指導。我們知道，幾乎所有出現延長跡象的患者都是早期出現的，並且會得到適當的監測和治療。這與我們的現實世界經驗非常一致。

As I said, we'll be reporting on some of that later in this year. We, of course, have very extensive safety surveillance systems in place. But we're really not hearing any evidence of concerns with standard guidelines and management of those patients. So, things are progressing very well.

正如我所說，我們將在今年稍後報告其中的一些內容。當然，我們已經建立了一個非常廣泛的安全監控系統。但我們確實沒有聽到任何關於對這些患者的標準指導方針和管理表示擔憂的證據。所以，事情進展得很順利。

Great. And Keith, do you want to talk about the royalty, please?

偉大的。基思，你想談談版稅嗎？

Yes, Chloe. So with respect to your question about how to model the Niktimvo. So we've already achieved profitability. First full quarter sales, we mentioned that $36 million in net revenue, we reported $9 million in collaboration revenue. So we're already in a range of 25% to 30% from a gross contribution perspective. And like I said in my prepared remarks, we only expect that to grow.

是的，克洛伊。關於如何對 Niktimvo 進行建模的問題。所以我們已經獲利了。第一季的銷售額，我們提到淨收入為 3,600 萬美元，我們報告的合作收入為 900 萬美元。因此，從總貢獻角度來看，我們的貢獻率已經處於 25% 到 30% 的範圍內。正如我在準備好的發言中所說的那樣，我們只希望這一數字能夠成長。

With respect to the royalty, it's really easy. It's simply 13.8% of the net revenue that is reported by Incyte. So in second quarter, that represents $5 million in royalties paid on $9.4 million in collaboration revenue. We're using the effective interest rate method. So the cash paid to Royalty Pharma won't exactly match what we report on the P&L.

對於皇室來說，這真的很容易。這僅佔 Incyte 報告的淨收入的 13.8%。因此，在第二季度，這意味著在 940 萬美元的合作收入中支付了 500 萬美元的版稅。我們正在使用實際利率法。因此，支付給 Royalty Pharma 的現金與我們在損益表中報告的金額並不完全相符。

And then lastly, I think you asked about IPF. So, IPF, very important indication for us. We have a Phase II trial ongoing. We expect to fully enroll that trial this year, data next year. That's a big market opportunity. As you pointed out, there are some entrenched competitors, different mechanism of action brought by this drug, we think a very impactful one, about 150,000 patients into the market in the US, 280,000 worldwide.

最後，我想您問的是有關 IPF 的問題。因此，IPF 對我們來說是一個非常重要的指標。我們正在進行第二階段試驗。我們預計今年將全面招募該試驗，明年將公佈數據。這是一個巨大的市場機會。正如您所指出的，存在一些根深蒂固的競爭對手，這種藥物帶來了不同的作用機制，我們認為這是一個非常有影響力的因素，美國市場上約有 150,000 名患者，全球有 280,000 名患者。

So it's a big market. Patients are still in absolute need of new therapy, and we think we bring that with Niktimvo potentially with this mechanism. So we'll have those trial results, and we think we will meaningfully differentiate over time if those are obviously positive.

所以這是一個很大的市場。患者仍然絕對需要新的治療方法，我們認為 Niktimvo 有可能透過這種機制帶來這種治療。因此，我們將獲得這些試驗結果，我們認為，如果這些結果明顯是正面的，我們將隨著時間的推移進行有意義的區分。

Great, thank you very much.

太好了，非常感謝。

Mayank Mamtani, B. Riley Securities.

Mayank Mamtani，B. Riley Securities。

Congrats on the progress. Could you just clarify, and sorry if I missed that, if there's any real-world evidence you're planning to generate as you strengthen the case for Revuforj use as maintenance therapy post-transplant? And what's your expectation for duration of therapy there, say, relative to the four to six months you're seeing in pre-transplant? And I have a quick follow-up.

恭喜你取得進展。您能否澄清一下，如果我錯過了，請見諒，您是否計劃提供任何現實世界的證據來加強 Revuforj 作為移植後維持治療的案例？那麼您預期的治療持續時間是多久呢？相對於移植前的四到六個月？我有一個快速的後續行動。

Yes. Thank you. Thanks so much for your question. I'm going to let Nick address the real-world part.

是的。謝謝。非常感謝您的提問。我打算讓尼克來處理現實世界的部分。

Yes, we'll be presenting some relatively preliminary data from the series we've been monitoring towards the latter part of this year, second half of this year, we're looking forward to presenting. That will obviously include patients' demography, how they do on therapy, and importantly, also the proportion of patients that go on to transplant in the real world from these series and also those patients that then start on Revuforj after transplant.

是的，我們將在今年下半年、下半年展示我們一直在監測的系列中的一些相對初步的數據，我們期待著展示這些數據。這顯然包括患者的人口統計數據、他們的治療情況，更重要的是，還包括這些系列中在現實世界中進行移植的患者比例以及移植後開始使用 Revuforj 的患者比例。

So I think those will be important data. Obviously, as time goes by and our commercial experience increases, we'll be able to add to those data. But I think it will be interesting preliminary data, and we'll look forward to reporting those out. And I think they'll shed some light on some important questions.

所以我認為這些都會是重要的數據。顯然，隨著時間的推移和我們商業經驗的增加，我們將能夠增加這些數據。但我認為這將是有趣的初步數據，我們期待報告這些數據。我認為他們會對一些重要問題作出解釋。

And I'll just make a comment, I think, as you asked about what our assumptions are on post-transplant maintenance, what percentage of patients are likely to go on to transplant and then, of course, on what time frame. And I think we commented earlier about high percentage of patients going to transplant.

我想，正如您所問的，我們對移植後維護的假設是什麼，有多少比例的患者可能會繼續進行移植，當然，在什麼時間範圍內。我認為我們之前評論過接受移植的患者比例很高。

I think that's obviously very clear to us now and exciting. And then in terms of staying on therapy, physicians have repeatedly told us, one year to two years -- is what I said in my prepared remarks, one year to two years is pretty consistent. Could be longer. Some physicians say that they will keep them on indefinitely without a real compelling reason to take them off. And obviously, these patients are at high risk of relapse.

我認為現在這一點對我們來說顯然非常清楚並且令人興奮。然後，關於繼續治療，醫生一再告訴我們，一年到兩年——我在準備好的發言中說過，一年到兩年是相當一致的。可能會更長。一些醫生表示，如果沒有真正令人信服的理由停止使用，他們就會無限期地繼續使用它們。顯然，這些患者復發的風險很高。

So you want to keep them in remission as long as possible. That's the key goal. So I think an assumption you can make on average for maintenance that physicians are thinking about one year to two-year time frame.

因此，您希望盡可能長時間地保持他們的病情緩解。這是關鍵目標。因此，我認為您可以對維護做出平均假設，即醫生正在考慮一年到兩年的時間範圍。

Very helpful. And then on Niktimvo, can you just remind us what development milestones to look out for as you think about the therapy moving into earlier line GVHD? I believe the label is third line, fourth line, but the uptake is in earlier lines. But I was curious if any additional clinical data milestones we should be on the lookout for?

非常有幫助。然後關於 Niktimvo，您能否提醒我們，當您考慮將療法轉向早期 GVHD 時，要注意哪些發展里程碑？我相信標籤是第三行、第四行，但吸收是在前面的行。但我很好奇我們是否應該關注其他臨床數據里程碑？

Yes. Thank you. Nick, do you want to take the question?

是的。謝謝。尼克，你想回答這個問題嗎？

Yes. And just to recap, and we haven't guided specifically on the timelines. We have two important studies in the frontline setting, one in combination with dexamethasone. That's a Phase III with registrational intent.

是的。回顧一下，我們還沒有具體指導時間表。我們在前線環境中進行了兩項重要的研究，其中一項是與地塞米松聯合使用。這是具有註冊意向的第三階段。

Again, we haven't guidelines specifically on when that study will read out. And an important Phase II study as well in combination with Jakafi. And then obviously, our IPF randomized Phase II study, which is around 135 patients, we're anticipating we'll complete enrollment towards the latter part of this year and data in the second half of next year.

再次強調，我們還沒有關於何時公佈該研究結果的具體指導方針。並且與 Jakafi 共同進行了一項重要的 II 期研究。顯然，我們的 IPF 隨機 II 期研究涉及約 135 名患者，我們預計將在今年下半年完成招募，並在明年下半年完成資料收集。

Thank you.

謝謝。

This concludes our question-and-answer session. I will now turn the floor over to Mr. Michael Metzger for any additional comments or closing remarks.

我們的問答環節到此結束。現在我將把發言權交給麥可‧梅茲格先生，請他發表補充評論或結束語。

Thank you, all. We appreciate you all tuning in today to discuss our recent progress and the exciting milestones ahead. We look forward to seeing many of you at several investor conferences and events in the third quarter. And with that, have a great evening.

謝謝大家。我們感謝大家今天的收看，討論我們最近的進展和未來令人興奮的里程碑。我們期待在第三季的幾場投資者會議和活動中見到你們。祝大家有個愉快的夜晚。

The call has now concluded. Thank you for joining. You may now disconnect.

通話現已結束。感謝您的加入。您現在可以斷開連線。