Syndax Pharmaceuticals Inc (SNDX) 2023 Q3 法說會逐字稿

Good day, everyone, and welcome to the Syndax third quarter 2023 earnings conference call. Today's call is being recorded. At this time, I'd like to turn the call over to Sharon Klahre, Head of investor relations at Syndax Pharmaceuticals.

大家好，歡迎參加 Syndax 2023 年第三季財報電話會議。今天的通話正在錄音。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 third quarter 2023 financial and operating results. I'm Sharon Klahre, and with me this afternoon to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer; Dr. Neil Gallagher, President and Head of R&D; and Keith Golden, Chief Finance Officer.

謝謝運營商。歡迎並感謝大家今天加入我們，回顧 Syndax 的 2023 年第三季財務與營運表現。我是 Sharon Klahre，今天下午與我一起介紹公司最新進展並討論財務業績的是執行長 Michael Metzger； Neil Gallagher 博士，總裁兼研發主管；和財務長基思·戈爾登。

Also joining us on the call today for the question and answer session are Dr. Peter Ordentlich, Chief Scientific Officer; and Dr. Anjali Ganguli, Chief Business Officer. This call is accompanied by a slide deck that is posted on the Investor page of the company's website. You can now turn to our forward-looking statements on Slide 2.

首席科學官 Peter Ordentlich 博士也參加了今天的電話問答環節。以及首席商務官 Anjali Ganguli 博士。這次電話會議還附有一張幻燈片，張貼在該公司網站的投資者頁面上。現在您可以參閱投影片 2 上的前瞻性陳述。

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 of 1995, actual results may differ materially from those indicated by these 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, November 2, 2023, only.

在我們開始之前，我想提醒您，在這次電話會議中所做的任何非歷史性的陳述都被視為前瞻性陳述。根據 1995 年《私人證券訴訟改革法案》的含義，由於各種重要因素，包括公司最近的表格 10- 季度報告中風險因素部分討論的因素，實際結果可能與這些陳述所表明的結果存在重大差異。 Q 以及向SEC 提交的其他報告。所做的任何前瞻性陳述僅代表我們截至今天（2023 年 11 月 2 日）的觀點。

A replay of this call will be available on the company's website, www.syndex.com following its completion. With that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer, Syndex.

本次電話會議的重播將在會議結束後在公司網站 www.syndex.com 上提供。至此，我很高興將電話轉給 Syndex 執行長 Michael Metzger。

Thank you, Sharon, and thank you to everyone joining us on the webcast. This continues to be an exciting year for Syndax, and I look forward to sharing a number of updates with you on the significant progress we've made. Throughout the third quarter we delivered on key pipeline milestones that are highlighted on Slide 3, including reporting positive top line, AGAVE-201 pivotal data of axatilimab for the treatment of chronic graph versus host disease.

謝謝莎倫，也謝謝所有加入我們網路廣播的人。對於 Syndax 來說，今年仍然是令人興奮的一年，我期待與您分享我們所取得的重大進展的一些最新消息。在整個第三季度，我們實現了幻燈片 3 中強調的關鍵管道里程碑，包括報告 axatilimab 用於治療慢性圖與宿主疾病的積極頂線 AGAVE-201 關鍵數據。

We also reported positive top line pivotal AUGMENT-101 data for revumenib in adult and pediatric patients with relapsed refractory KMT2Ar rearranged acute leukemias. Together, these results put us on a clear path to becoming a commercial stage biopharmaceutical company in 2024 with two potentially first and best-in-class products.

我們也報告了 revumenib 在患有復發難治性 KMT2Ar 重排急性白血病的成人和兒童患者中的積極頂線關鍵 AUGMENT-101 數據。總而言之，這些結果使我們走上了一條清晰的道路，預計在 2024 年成為一家商業階段的生物製藥公司，並擁有兩種潛在的一流產品。

We are also happy to provide data today from additional relapsed or refractory NPM1 patients that were enrolled in the final stages of the Phase 1 portion of the AUGMENT-101 trial. Neil walks us through the data a little later in this call. But in summary, we are encouraged by the 36% CR/CRh rate and deep responses that we are seeing in the NPM1 population.

我們今天也很高興提供其他復發或難治性 NPM1 患者的數據，這些患者已入組 AUGMENT-101 試驗 1 期部分的最後階段。尼爾稍後會在這次電話會議中向我們介紹這些數據。但總而言之，我們對 NPM1 族群中 36% 的 CR/CRh 率和深度反應感到鼓舞。

Responses elicited by revumenib in the NPM1 population are durable with some patients in remission beyond 22 months, further supporting the rationale that revumenib can provide a meaningful benefit to NPM1 patients and emphasizing is blockbuster commercial potential across both KMT2A and NPM1 acute leukemia.

revumenib 在NPM1 族群中引起的反應是持久的，有些患者的緩解超過22 個月，進一步支持revumenib 可以為NPM1 患者提供有意義的益處的基本原理，並強調了它在KMT2A 和NPM1 急性白血病方面具有巨大的商業潛力。

We continue our positive momentum heading into the end of 2023 with a primary focus on completing two potential regulatory filings by year end and launching both drugs in 2024. This will put Syndax in a very unique position to create value as a mid-cap biotech company.

到2023 年底，我們將繼續保持積極勢頭，主要重點是在年底前完成兩項潛在的監管備案，並在2024 年推出這兩種藥物。這將使Syndax 處於非常獨特的地位，可以作為中型生物技術公司創造價值。

We will have a significant presence at the American Society of Hematology, ASH annual meeting, including at our planned investor event and expect to provide several data updates on both these programs at that time. I am pleased to share that as of a few days ago, we initiated the NDA submission of revumenib for KMT2A acute leukemia under the FDA's real-time oncology review program or RTOR, we view RTOR as a significant benefit for the revumenib program. It complements our BTD and fast-track status for KMT2A and provides a more efficient review process to ensure that revumenib is available to patients as early as possible.

我們將在美國血液學會 ASH 年會上發揮重要作用，包括我們計劃的投資者活動，並預計屆時將提供有關這兩個項目的多項數據更新。我很高興地告訴大家，幾天前，我們根據 FDA 的即時腫瘤學審查計劃或 RTOR 啟動了 revumenib 治療 KMT2A 急性白血病的 NDA 提交，我們認為 RTOR 是 revumenib 計劃的一個重大益處。它補充了我們 KMT2A 的 BTD 和快速通道狀態，並提供了更有效的審查流程，以確保患者儘早獲得 revumenib。

Under our tour, the sponsor has consistent engagement with the FDA throughout the submission process. Drugs are accepted for review into this program need to meet specific eligibility criteria. The most of important of which is the likelihood of demonstrating substantial improvement over available therapy.

在我們的考察中，申辦者在整個提交過程中與 FDA 保持一致的接觸。接受該計劃審查的藥物需要滿足特定的資格標準。其中最重要的是，與現有療法相比，有可能出現實質改善。

In accordance with FDA guidance for AML and in line with the approvals of other AML agents in the relapsed refractory setting, we anticipate revumenib would be granted full approval based on the results of AUGMENT-101. With our partner insight, we also remain on track to complete the BLA filing for axatilimab by year end.

根據 FDA 對 AML 的指導，並與其他 AML 藥物在復發難治性疾病中的批准一致，我們預計 revumenib 將根據 AUGMENT-101 的結果獲得完全批准。憑藉我們合作夥伴的洞察力，我們也有望在年底前完成 axatilimab 的 BLA 備案。

As you saw from our press release earlier today, data from both the AGAVE-201 and AUGMENT-101 pivotal trials, including post-transplant maintenance data, along with revumenib combination data from the same trial will be presented at the ASH meeting in December. Beyond the Congress presentation, we will also have the opportunity to share additional data from ongoing revumenib combination trials at our ASH investor events, which will further reinforce revumenib compelling clinical profile and meaningfully add to its value proposition.

正如您從今天早些時候的新聞稿中看到的，AGAVE-201 和AUGMENT-101 關鍵試驗的數據，包括移植後維護數據，以及來自同一試驗的revumenib 組合數據，將在12 月的ASH 會議上公佈。除了在大會上的演講之外，我們還將有機會在ASH 投資者活動中分享正在進行的revumenib 組合試驗的更多數據，這將進一步強化revumenib 引人注目的臨床概況，並有意義地增加其價值主張。

We are well-funded with $379 million in cash as of September 30. Our current balance sheet not only supports our planned commercial launches and the trials that we have outlined, but also allows us to expand beyond our core registration indications and pursue select business development opportunities.

截至9 月30 日，我們資金充足，擁有3.79 億美元現金。我們目前的資產負債表不僅支持我們計劃的商業啟動和我們概述的試驗，還使我們能夠擴展到核心註冊適應症之外並追求精選業務發展機會。

Now let's dive into revumenib our highly selective main inhibitor. I'll ask Neil to provide a recap of the results from the AUGMENT-101 pivotal trial to speak to the ASH abstracts and review the data from the NPM1 patients in the Phase 1 portion of the AUGMENT-101 trial. Neil.

現在讓我們深入了解 revumenib 我們的高選擇性主要抑制劑。我將請 Neil 概述 AUGMENT-101 關鍵試驗的結果，以討論 ASH 摘要，並檢視 AUGMENT-101 試驗第一階段部分 NPM1 患者的數據。尼爾.

Thank you, Michael. I will now review the AUGMENT-101 pivotal data in relapsed or refractory KMT2A acute leukemia beginning on Slide 4. As previously reported, the independent data monitoring committee reviewed the data and recommended that trial stop early for efficacy in accordance with a predefined interim analysis.

謝謝你，麥可。我現在將從幻燈片4 開始回顧復發或難治性KMT2A 急性白血病的AUGMENT-101 關鍵數據。如之前報導的，獨立數據監測委員會審查了數據，並建議根據預定義的中期分析提前停止試驗以提高療效。

We are very pleased with the robustness of the data that we reported. Almost two-thirds of these heavily pretreated patients achieved clinically significant responses, enabling many to receive potentially curative transplant. Importantly, high proportion of responders in the trial were started on revumenib in the post-transplant maintenance setting.

我們對我們報告的數據的穩健性感到非常滿意。這些經過大量預處理的患者中，近三分之二獲得了臨床上顯著的緩解，使許多人能夠接受潛在的治癒性移植。重要的是，試驗中很大一部分應答者在移植後維持環境中開始使用瑞維美尼。

The desire for physicians to restart revumenib its post-transplant maintenance speaks to its efficacy and tolerability and their belief that it may offer a better outcome for their KMT2A acute leukemia patients. Importantly, the ability of these heavily pretreated patients to both respond to and tolerate revumenib of therapy also underscores its potential to be adopted into frontline combinations.

醫生希望重新啟動 revumenib 的移植後維持治療，這說明了它的功效和耐受性，並且他們相信它可以為 KMT2A 急性白血病患者提供更好的結果。重要的是，這些經過大量預處理的患者對瑞美尼治療有反應和耐受的能力也強調了其被採用到一線組合中的潛力。

Turning to Slide 5. The majority of patients in the efficacy evaluable population, which include adult and pediatric AML and ALL patient achieved clinically significant responses to treatment with a high overall response rate of 63%. The CR/CRh rate in this population was 23%.

轉向幻燈片 5。療效可評估人群中的大多數患者（包括成人和兒童 AML 和 ALL 患者）對治療取得了臨床顯著反應，總體反應率高達 63%。該族群的 CR/CRh 率為 23%。

The response rates observed in KMT2A AML specifically were consistent with those in the overall efficacy evaluable population with 65% achieving a response and 24.5% achieving CR or CRh. The MRD-negative rate among CR/CRh responders was also impressive at 70% at the time of the data cutoff, the median duration of CR/CRh response of 6.4 months across both the efficacy evaluable and AML populations with 46% or six patients remaining in response. Of note, this is a Kaplan-Meier estimate, and the data will continue to mature over time. Therefore, the median DOR may extend beyond 6.4 months with additional follow-up.

在 KMT2A AML 中觀察到的緩解率與整體療效可評估人群中的緩解率一致，其中 65% 實現緩解，24.5% 實現 CR 或 CRh。 CR/CRh 應答者中的MRD 陰性率在數據截止時也高達70%，令人印象深刻，療效可評估人群和AML 人群中CR/CRh 應答的中位數持續時間均為6.4 個月，其中46%或仍有6 名患者作為回應。值得注意的是，這是 Kaplan-Meier 的估計，數據將隨著時間的推移而不斷成熟。因此，如果進行額外的隨訪，中位 DOR 可能會延長至 6.4 個月以上。

Turning to Slide 6 not only did we observe a high overall response rate of 63%, but 39% of responding patients proceeded to bone marrow transplant, which is notably higher than historical benchmark in this population of less than 5%. Eight patients were transplanted prior to achieving CR/CRh at the discretion of the attending physician.

轉向幻燈片 6，我們不僅觀察到 63% 的高總體緩解率，而且有 39% 的緩解患者進行了骨髓移植，這明顯高於該人群中不到 5% 的歷史基準。八名患者在達到 CR/CRh 之前根據主治醫生的判斷進行了移植。

Clearly, if physicians had decided to wait a little longer prior to transplant than more of these patients could have achieved a best response CR/CRh, for example, if all eight of these patients had achieved CR/CRh, then the rate would have been 37%. 71% of these patients, 10 of 14 either restarted a revumenib or were eligible to restart as maintenance therapy.

顯然，如果醫生決定在移植前等待一段時間，那麼更多的患者可能會達到最佳緩解 CR/CRh，例如，如果所有八名患者都達到 CR/CRh，那麼比率將會是37%。其中 71% 的患者（14 名患者中的 10 名）要么重新開始瑞維美尼治療，要么有資格重新開始維持治療。

At the time of data cutoff, some patients were treated in the maintenance portion for as long as eight months on several are continuing on therapy, which we believe speaks to revumenib compelling overall clinical profile and the potential for long-term maintenance in this setting.

截至數據截止時，一些患者在維持部分接受了長達八個月的治療，其中一些患者正在繼續接受治療，我們相信這說明了revumenib 令人信服的整體臨床特徵以及在這種情況下長期維持的潛力。

The ability already mounted to rapidly induce blast free responses in heavily pretreated patients, thereby enabling them to undergo potentially curative bone marrow transplant, followed by post-transplant maintenance represents a potential paradigm shift in the standard of care in this setting.

在經過大量預處理的患者中，已經具備快速誘導無母細胞反應的能力，從而使他們能夠接受潛在的治癒性骨髓移植，然後進行移植後維護，這代表了這種情況下護理標準的潛在範式轉變。

We have a presentation at the ASH meeting that will highlight revumenib for post-transplant maintenance including patients on therapy in remission beyond 18 months. The data from AUGMENT-101 indicate that revumenib is well tolerated and the safety profile is consistent with what is -- what was previously reported.

我們在 ASH 會議上做了一次演講，重點介紹了 revumenib 在移植後維持治療中的應用，包括接受治療緩解超過 18 個月的患者。 AUGMENT-101 的數據顯示 revumenib 具有良好的耐受性，且安全性與先前報告的一致。

We believe that the emerging benefit risk profile of revumenib supports its use not only as a monotherapy in the relapsed refractory setting before and after transplant, but also its potential use in combination with frontline standards of care for which initial data are forthcoming -- will be forthcoming later this year.

我們相信，revumenib 正在出現的獲益風險狀況不僅支持其在移植前後作為複發難治性病例的單一療法，而且還支持其與即將公佈的初始數據的一線護理標準相結合的潛在用途。今年晚些時候推出。

Turning to Slide 7. Today, we announced encouraging data from three additional patients with NPM1 mutated relapsed or refractory AML included in the Phase 1 portion of the AUGMENT-101 trial for total of 14 NPM1 patients treated at doses meeting the RP2D criteria. These patients who are enrolled in Phase 1 to complete the pharmacokinetic characterization of revumenib. Among these 14 patients, 7 achieved a response to treatment for a 50% overall response rate. 5 of 14 achieved a CR/CRh rate of 36% and 100% of the CR/CRh responders were MRD-negative.

轉向幻燈片7。今天，我們宣布了來自AUGMENT-101 試驗1 期部分的另外3 名NPM1 突變復發或難治性AML 患者的令人鼓舞的數據，總共14 名NPM1 患者接受了符合RP2D 標準的劑量治療。這些患者被納入第一階段，以完成 revumenib 的藥物動力學特徵。在這 14 名患者中，有 7 名患者對治療有反應，整體反應率為 50%。 14 人中有 5 人的 CR/CRh 率為 36%，且 100% 的 CR/CRh 應答者均為 MRD 陰性。

On Slide 8, you may see that these responses are durable with four or five of the patients remaining in response three already beyond six months, one beyond 22 months and one over 30 months at the time of the analysis. Revumenib also enabled 43% of NPM1 responders to proceed to transplant. One of the patients who proceeded to transplant have been enrolled following the AUGMENT-101 protocol update, which allowed patients to restart revumenib post-transplant. This patient remains on revumenib maintenance at the time of the analysis.

在投影片8 上，您可能會看到這些反應是持久的，在分析時，四到五名患者仍處於反應狀態，其中三位已經超過6 個月，一位超過22 個月，一位超過30 個月。 Revumenib 也使 43% 的 NPM1 反應者能夠進行移植。其中一名進行移植的患者已在 AUGMENT-101 方案更新後入組，該方案允許患者在移植後重新啟動 revumenib。在分析時，該患者仍在接受瑞維美尼維持治療。

Similar to the Phase 2 results observed with KMT2A population revumenib is well tolerated in patients with relapsed refractory NPM1 AML. There were no grade 4 or 5 QT prolongations. No patients experienced more than grade 2 differentiation syndrome and no patients discontinued due to treatment-related adverse events.

與 KMT2A 群體觀察到的 2 期結果類似，revumenib 在復發難治性 NPM1 AML 患者中具有良好的耐受性。沒有出現 4 級或 5 級 QT 延長。沒有患者出現超過 2 級的分化綜合徵，也沒有患者因治療相關不良事件而停藥。

As Michael said earlier, these data continue to support our conviction revumenib will be an important treatment for NPM1 AML as well as from KMT2A acute leukemias. And we expect that NPM1 one pivotal trial results will be consistent with the data generated to date and highly supportive of a first to market approval.

正如 Michael 之前所說，這些數據繼續支持我們的信念，revumenib 將成為 NPM1 AML 以及 KMT2A 急性白血病的重要治療方法。我們預計 NPM1 的一項關鍵試驗結果將與迄今為止產生的數據一致，並高度支持首次上市批准。

The pivotal cohort of the AUGMENT-101 trial continues to enroll relapse refractory NPM1 mutant AML patients. The trial is designed to enroll 64 patients and up to 20 pediatric patients. While the trial continues to recruit well in the US and internationally, we now forecast completion of enrollment in the late first quarter or early second quarter next year. Due to a few high enrolling sites in Europe coming online later than we expected in the third quarter. Coupled with the recent events in Israel, where we have a high concentration of sites. I would note that Israel accounts for 16% of our enrolling sites, and historically these have been very high enrolling. We are now looking to make up for any potential shortfall at our sites, but it's difficult for us to predict the impact that the evolving geopolitical situation may have on enrollment.

AUGMENT-101 試驗的關鍵隊列繼續招募復發難治性 NPM1 突變 AML 患者。該試驗旨在招募 64 名患者和最多 20 名兒科患者。雖然該試驗繼續在美國和國際上招募，但我們現在預計將在明年第一季末或第二季初完成招募。由於歐洲一些高註冊網站在第三季上線的時間晚於我們的預期。再加上最近在以色列發生的事件，我們在那裡的地點高度集中。我要指出的是，以色列占我們招生網站的 16%，而且從歷史上看，這些網站的註冊人數一直非常高。我們現在正在尋求彌補我們網站上任何潛在的短缺，但我們很難預測不斷變化的地緣政治局勢可能對入學的影響。

Nonetheless, we expect to be in a position to report data in the fourth quarter of 2024 and importantly, continue to look forward to potential approval in 2025 based on an sNDA filing following revumenib anticipated initial approval in KMT2A.

儘管如此，我們預計能夠在 2024 年第四季報告數據，重要的是，根據 revumenib 預計在 KMT2A 初步批准後提交的 sNDA 備案，我們繼續期待 2025 年可能獲得批准。

Turning to Slide 9. In addition to sharing the AUGMENT-101 pivotal data at ASH, we look forward to Dr. Issa highlighting his safe trial result in an oral presentation on Saturday morning during the meeting. This is an investigator-sponsored Phase 1b trial conducted by Dr. Issa at the MD Anderson Cancer Center, evaluating an all oral combination of revumenib with venetoclax and a fixed dose combination of the cecitabine and cetadiridine in children and adults with relapsed refractory AML or mixed phenotype acute leukemias.

轉向幻燈片 9。除了在 ASH 上分享 AUGMENT-101 關鍵數據外，我們期待 Issa 博士在周六上午的會議期間的口頭演示中強調他的安全試驗結果。這是一項由研究者資助的1b 期試驗，由MD 安德森癌症中心的Issa 博士進行，評估了revumenib 與Venetoclax 的全口服組合以及西西他濱和西他啶的固定劑量組合對患有復發難治性AML 或混合性AML 的兒童和成人的影響。表型急性白血病。

At the time of the data cutoff, the trial was enrolling at the current monotherapy RP2D of 163 milligrams every 12 hours with a strong CYP3A4 inhibitor. In total eight patients with either NPM1, KMT2A or NUP98 mutations were enrolled in the trial, having received 2.5 median prior lines of therapy, approximately two thirds of patients received prior venetoclax.

截至數據截止時，該試驗正在以目前每 12 小時 163 毫克的強效 CYP3A4 抑制劑單一療法 RP2D 入組。共有 8 名攜帶 NPM1、KMT2A 或 NUP98 突變的患者參加了該試驗，他們之前接受過 2.5 次中位治療，其中大約三分之二的患者之前接受過維奈托克治療。

All patients on a strong CYP3A4 inhibitor and were on a strong CYP3A4 inhibitor and therefore treated with revumenib in either 113 milligrams Q12 early or 160 milligrams, -- 63 milligrams Q12 of early. Seven of eight patients were evaluable for response. All seven 100% achieved response six of seven achieved CRC and two of seven 28% achieved CR/CRh. Importantly, responses were observed across relapsed or refractory NPM1, KMT2A or NUP98 acute leukemia patients.

所有患者均接受強效 CYP3A4 抑制劑治療，且均接受強效 CYP3A4 抑制劑治療，因此在早期接受 113 毫克 Q12 或 160 毫克（早期 Q12 63 毫克）revumenib 治療。八名患者中有七名可以評估反應。所有 7 名 100% 的患者均達到了緩解，7 名患者中有 6 名獲得了 CRC，7 名 28% 的患者中有 2 名獲得了 CR/CRh。重要的是，在復發或難治性 NPM1、KMT2A 或 NUP98 急性白血病患者中觀察到了反應。

Three patients conditioned to hemakudic stem cell transplantation following response and to continue in remission and have started maintenance as of the data cutoff. We are highly encouraged by the combinability of revumenib with venetoclax and hypomethylating agent in this trial. This combination was well tolerated at active doses, including the current monotherapy RP2D. I'll now turn the call back to Michael.

三名患者在緩解後接受 hemakudic 幹細胞移植並持續緩解，截至數據截止時已開始維持治療。在本次試驗中，revumenib 與 Venetoclax 和低甲基化劑的組合使我們深受鼓舞。該組合在活性劑量下具有良好的耐受性，包括目前的單一療法 RP2D。我現在將電話轉回給邁克爾。

Thank you, Neil. Turning to slide 10. We believe the revumenib could form the backbone of treatment for patients with KMT2A rearranged and NPM1 mutant acute leukemias. And as demonstrated by its compelling efficacy and safety profile, we have expanded our clinical strategy beyond the relapsed or refractory setting into earlier settings and post-transplant maintenance, including combinations with approved therapies.

謝謝你，尼爾。轉向幻燈片 10。我們相信 revumenib 可以成為治療 KMT2A 重排和 NPM1 突變急性白血病患者的支柱。正如其令人信服的功效和安全性所證明的那樣，我們已將我們的臨床策略從復發或難治性環境擴展到早期環境和移植後維持，包括與已批准的療法的組合。

In an attempt to accelerate the generation of evidence of clinical benefits seen with revumenib across various settings of KMT2A and NPM1 acute leukemias. We are collaborating with cooperative groups and leading investigators in addition to the clinical trials that Syndax is conducting.

試圖加速產生 revumenib 在 KMT2A 和 NPM1 急性白血病的各種情況下的臨床益處的證據。除了 Syndax 正在進行的臨床試驗之外，我們還與合作團體和主要研究人員合作。

In addition to the SAVE trial that Neil described earlier, we plan to present initial data from the Beat AML and AIGMENT-102 trials in the fourth quarter at our planned investor event at ASH. The Phase 1 Beat AML trial as part of our collaboration with the Leukemia and Lymphoma Society and revumenib is being combined with venetoclax and azacytidine to treat newly diagnosed AML patients who are unfit for induction chemotherapy.

除了 Neil 先前描述的 SAVE 試驗之外，我們還計劃在第四季度在 ASH 計畫的投資者活動中展示 Beat AML 和 AIGMENT-102 試驗的初始數據。作為我們與白血病和淋巴瘤協會合作的一部分，1 期 Beat AML 試驗將 revumenib 與 Venetoclax 和 azacytidine 聯合治療不適合誘導化療的新診斷 AML 患者。

Enrollment is ongoing in the dose-finding stage of the trial to confirm the RP2D for this combination. And we continue to expect to share data on safety and efficacy from the trial at our ASH investor event.

試驗的劑量探索階段正在進行招募，以確認該組合的 RP2D。我們繼續期望在 ASH 投資者活動中分享該試驗的安全性和有效性數據。

The AUGMENT-102 trial is designed to assess the safety of revumenib in combination with standard salvage chemotherapies for patients with relapse or refractory acute leukemias. We anticipate presenting an update on the initial safety and potential RP2D from the trial at our ASH investor event.

AUGMENT-102 試驗旨在評估 revumenib 與標準挽救化療聯合治療復發或難治性急性白血病患者的安全性。我們預計在 ASH 投資者活動中介紹試驗的初始安全性和潛在 RP2D 的最新情況。

We look forward to initiating a trial of revumenib in combination with standard of care intensive chemotherapy known as seven plus three in newly diagnosed patients with acute leukemia in late 2023 or early 2024. This trial will also include an option for maintenance with revumenib monotherapy.

我們期待於2023 年底或2024 年初在新診斷的急性白血病患者中啟動一項Revumenib 與標準護理強化化療（稱為「七加三」）相結合的試驗。該試驗還將包括Revumenib 單藥維持治療的選擇。

Beyond the acute leukemia trials we've laid out here. We are rolling a proof-of-concept signal seeking Phase 1 clinical trial in metastatic colorectal cancer based on compelling preclinical science supporting the role of the menin-KMT2A interaction and beta continued driven tumors. The trial is advancing nicely through the dose escalation phase, and we are nearing an RP2D.

除了我們在這裡列出的急性白血病試驗之外。我們正在進行一項針對轉移性結直腸癌的概念驗證訊號尋求 1 期臨床試驗，該試驗基於支持 menin-KMT2A 相互作用和 β 持續驅動腫瘤的作用的令人信服的臨床前科學。該試驗在劑量遞增階段進展順利，我們即將進入 RP2D。

We would perceive responses or prolonged stable disease as encouraging this difficult to treat patient population with the market with a monotherapy, and we expect to follow these patients to gather sufficient efficacy into 2024. We anticipate being able to provide an update on the progress of the dose escalation phase of the trial in the first quarter of 2024.

我們認為緩解或長期穩定的疾病會鼓勵市場上使用單一療法治療這種難以治療的患者群體，並且我們期望對這些患者進行跟踪，以在2024 年獲得足夠的療效。我們預計能夠提供有關進展的最新資訊試驗的劑量遞增階段將於 2024 年第一季進行。

Now the slide 11, KMT2A and NPM1 acute leukemias represent up to 40% of AML patients, and there are no FDA approved targeted therapies for this population, including the expansion opportunities there is the potential to address upwards of 12,000 NPM1 mutant and KMT2A rearranged acute leukemia patients across various settings.

現在幻燈片11，KMT2A 和NPM1 急性白血病佔AML 患者的比例高達40%，並且FDA 還沒有批准針對該人群的標靶治療，包括有可能解決超過12,000 個NPM1 突變體和KMT2A 重排急性白血病的擴展機會不同環境下的白血病患者。

We are committed to bringing these encouraging clinical benefits to even more patients as this remains an area with significant unmet needs. We believe relapse or refractory KMT2A acute leukemias alone represent a $650 to $750 million market opportunity in the US based on the estimated patient population, duration of treatment and current pricing assumptions.

我們致力於為更多患者帶來這些令人鼓舞的臨床益處，因為這仍然是一個尚未滿足重大需求的領域。我們認為，根據估計的患者人數、治療持續時間和當前的定價假設，僅復發或難治性 KMT2A 急性白血病就在美國代表了 650 至 7.5 億美元的市場機會。

KMT2A rearrangements represent approximately 10% of AML and ALL, which translates into an incidence of approximately 2600 KMT2A rearranged acute leukemia patients, a very high percentage of whom are refractory to frontline standard of care treatments.

KMT2A 重排約佔 AML 和 ALL 的 10%，這意味著大約 2600 名 KMT2A 重排急性白血病患者的發生率很高，其中很大一部分對一線標準護理治療難以治療。

Based on the enthusiasm we are hearing from physicians and the potential to shift the treatment paradigm in KMT2A to incorporate maintenance treatment post-transplant. We believe the median duration of therapy across the treatment population would be approximately nine months. And we believe the data generated in AUGMENT-101 support pricing, competitive with or above other targeted therapies in AML, such as FLT3 or IDH inhibitors.

基於我們從醫生那裡聽到的熱情以及改變 KMT2A 治療模式以納入移植後維持治療的潛力。我們認為治療族群的中位治療持續時間約為九個月。我們相信 AUGMENT-101 中產生的數據支持定價，與 AML 的其他標靶療法（例如 FLT3 或 IDH 抑製劑）相比具有競爭力或優於其他療法。

With no treatment options approved for these patients and no near term competition revumenib could easily become the treatment of choice for all patients with KMT2A acute leukemia based on obtaining the only age and disease agnostic label and KMT2A acute leukemia.

由於沒有批准用於這些患者的治療方案，並且沒有近期的競爭性藥物，基於獲得唯一的年齡和疾病不可知標籤和 KMT2A 急性白血病，瑞維美尼很容易成為所有 KMT2A 急性白血病患者的治療選擇。

We expect that our first mover advantage and experienced physicians will gain treating their patients with revumenib could extend meaningfully beyond KMT2A and allow us to build a formidable franchise in the next few years. Supported by the compelling NPM1 data we presented today, we believe revumenib will also provide meaningful benefit in relapse or refractory NPM1 patients.

我們預計，我們的先發優勢和經驗豐富的醫生將能夠用 revumenib 治療患者，從而有意義地擴展到 KMT2A 之外，並使我們能夠在未來幾年內建立強大的特許經營權。在我們今天提供的令人信服的 NPM1 數據的支持下，我們相信 revumenib 也將為復發或難治性 NPM1 患者提供有意義的益處。

Our market research suggests that if approved, oncologists are likely to reach for revumenib as either their second- or third-line agent of choice for patients with NPM1 mutant AML. We estimate that this population would be slightly larger than relapsed refractory KMT2A acute leukemia population. And based on our Phase 1 results, we also believe overall efficacy and treatment duration will be consistent between the KMT2A and NPM1 populations.

我們的市場研究表明，如果獲得批准，腫瘤學家可能會選擇 revumenib 作為 NPM1 突變 AML 患者的二線或三線藥物。我們估計該族群將略大於復發難治性 KMT2A 急性白血病族群。根據我們的 1 期結果，我們也相信 KMT2A 和 NPM1 族群的整體療效和治療持續時間將是一致的。

Having first mover access to two distinct market segments in acute leukemias, KMT2A and NPM1 creates a total accessible population of 5,000 to 6,000 patients in the relapsed refractory setting and an addressable market opportunity of approximately $1 billion to $1.5 billion for revumenib in the US alone. We anticipate that revumenib will begin to carve out a dominant share of the relapse and refractory NPM1 market starting in 2025.

KMT2A 和NPM1 率先進入急性白血病兩個不同的細分市場，為復發難治性患者創造了5,000 至6,000 名患者的總可用人群，僅在美國，revumenib 就創造了約10 億至15 億美元的潛在市場機會。我們預計，從 2025 年開始，revumenib 將開始在復發和難治性 NPM1 市場中佔據主導地位。

Now let's dive into axatilimab, our monoclonal antibody targeting the CSF-1 receptor beginning on Slide 12. In collaboration with Incyte, we shared positive results from the global pivotal AGAVe-201 trial evaluating the efficacy, safety and tolerability of axatilimab in 241 patients with active chronic GVHD whose disease had progressed after at least two prior therapies.

現在讓我們深入了解axatilimab，這是我們從幻燈片12 開始的針對CSF-1 受體的單株抗體。我們與Incyte 合作，分享了全球關鍵AGAVe-201 試驗的積極結果，該試驗評估了axatilimab 在241 名患有以下疾病的患者中的有效性、安全性和耐受性：活動性慢性 GVHD，其疾病在至少兩次既往治療後出現進展。

As a reminder, the trial met its primary endpoint of overall response rate by cycle seven day one using the 2014 NIH consensus criteria for chronic GVHD across all three dose groups, the overall response rate or overall ORR was 74% at a dose of 0.3 milligrams per kilogram administered every two weeks.

提醒一下，該試驗使用2014 年NIH 所有三個劑量組的慢性GVHD 共識標準，在第7 天的第一個週期達到了總體緩解率的主要終點，在0.3 毫克的劑量下，總體緩解率或總體ORR 為74%每公斤每兩週施用一次。

The responses were durable with a median duration of response, not yet reached at the time of data cutoff and 60% of responders were still responding at one year. Axatilimab was well tolerated in the trial with a low 6% rate of discontinuations and the most common adverse events were consistent with the on-target effects that were observed in prior trials.

這些反應是持久的，反應持續時間中位數在數據截止時尚未達到，60% 的反應者在一年後仍在反應。 Axatilimab 在試驗中耐受性良好，停藥率低至 6%，最常見的不良事件與先前試驗中觀察到的中靶效應一致。

I want to remind you that robust efficacy was observed despite the patients being very advanced and heavily pretreated. As an example, I would highlight that there are meaningful differences in patient populations between the axatilimab AGAVE-201 trial and Rezurock ROCKstar trial, both of which targeted patients with chronic GVHD who had received two or more prior lines of therapy.

我想提醒您的是，儘管患者已處於晚期且經過大量預處理，但仍觀察到了強勁的療效。作為一個例子，我想強調的是，axatilimab AGAVE-201 試驗和 Rezurock ROCKstar 試驗之間的患者群體存在顯著差異，這兩項試驗都針對既往接受過兩種或多種治療的慢性 GVHD 患者。

Notably patients in the AGAVE-201 trial had a longer median time since diagnosis more severe chronic GVHD and had received more prior lines of therapy, including a greater number of patients have received Jackifi than patients included in the Rezurock trial.

值得注意的是，AGAVE-201 試驗中的患者自診斷出更嚴重的慢性GVHD 以來的中位數時間更長，並且之前接受過更多的治療，其中接受Jackifi 治療的患者數量比Rezurock 試驗中的患者更多。

We believe these points of differentiation underscore just how impressive the AGAVE-201 trial results are and points to the significant value axatilimab could bring to patients if approved. These results not only support the promise of axatilimab safety and efficacy profile, but reinforced potential as a first and best in class CSF1R monoclonal antibody in chronic GVHD.

我們相信這些差異點強調了 AGAVE-201 試驗結果的令人印象深刻，並表明 axatilimab 如果獲得批准可以為患者帶來重大價值。這些結果不僅支持了axatilimab安全性和有效性的承諾，也增強了作為治療慢性GVHD的首個、同類最佳CSF1R單株抗體的潛力。

Axatilimab is the first investigational chronic GVHD treatment to target inflammation and fibrosis through the inhibition of disease-associated macrophages and the AGAVE-201 data demonstrates the potentially pronounced impact as mechanism alone or in combination with standard of care therapies already available for the management of this disease may have on patients suffering from chronic graft versus host disease. In collaboration with Incyte, we intend to file a BLA by year end 2023. Additionally, we look forward to showcasing the full results during the plenary session at ASH.

Axatilimab 是第一個透過抑制疾病相關巨噬細胞來靶向發炎和纖維化的研究性慢性GVHD 治療方法，AGAVE-201 數據表明，作為單獨的機製或與已經可用於管理這一問題的標準護理療法相結合，具有潛在的顯著影響疾病可能對患有慢性移植物抗宿主疾病的患者產生影響。我們計劃與 Incyte 合作，在 2023 年底之前提交 BLA。此外，我們期待在 ASH 全體會議上展示完整結果。

Turning to slide 13, approximately 14,000 US patients suffer from chronic graft versus host disease, 50% of whom require treatment beyond second line due to disease progression, inadequate response or disease manifestations that aren't wholly addressed with current treatments.

轉向投影片 13，約 14,000 名美國患者患有慢性移植物抗宿主疾病，其中 50% 由於疾病進展、反應不足或目前治療無法完全解決的疾病表現，需要二線以外的治療。

Unfortunately, there are no cures for this advanced population of chronic GVHD patients. Patients are initially treated with corticosteroids and then cycled through a variety of additional therapies. While patients may be treated with several of the approved therapies the order in which they are used may depend on the physician's experience and how a given agent may address specific manifestations of the disease.

不幸的是，對於這群晚期慢性 GVHD 患者，目前還沒有治癒方法。患者最初接受皮質類固醇治療，然後循環接受其他各種治療。雖然患者可以使用幾種已批准的療法進行治療，但使用順序可能取決於醫生的經驗以及給定藥物如何解決疾病的特定表現。

Jackifi and Rezurock have had successful commercial launches, which speaks to the unmet need in chronic GVHD. That translates to a substantial commercial opportunity. It is our conviction that axatilimab could provide an effective, differentiated practice-changing intervention for this underserved population.

Jackifi 和 Rezurock 已成功商業化上市，這說明慢性 GVHD 的需求尚未滿足。這意味著巨大的商業機會。我們相信，axatilimab 可以為這一服務不足的人群提供有效的、差異化的改變實踐的干預措施。

Axatilimab suppresses monocyte derived macrophage activation and proliferation, which may provide more comprehensive control of the disease than currently approved therapies. This is a key differentiator and also supports moving axatilimab earlier in the treatment paradigm to potentially prevent organ damage before it occurs.

Axatilimab 抑制單核細胞衍生的巨噬細胞活化和增殖，這可能比目前批准的療法更全面地控制該疾病。這是一個關鍵的區別因素，也支持將 axatilimab 納入治療模式的早期，以潛在地在器官損傷發生之前預防其發生。

Because axatilimab is an antibody drug-drug interactions are expected to be minimal and axatilimab unique mechanism of action may offer the benefit of being an ideal combination partner with standard of care therapies currently used for the treatment of chronic GVHD.

由於 axatilimab 是一種抗體藥物，藥物交互作用預計極小，並且 axatilimab 獨特的作用機制可能會帶來成為目前用於治療慢性 GVHD 的標準護理療法的理想組合夥伴的優勢。

The opportunity to expand to ex-US markets and additional high-value indications as well as combinations in earlier settings and chronic GVHD, both in adult and pediatric could built significant additional value for axatilimab.

擴展到美國以外市場的機會和其他高價值適應症以及成人和兒童早期環境和慢性 GVHD 的組合可能會為 axatilimab 帶來顯著的附加價值。

We are looking forward to the initiation of additional trials of axatilamab, including a 26 week randomized placebo-controlled Phase 2 trial in 135 idiopathic pulmonary fibrosis patients expected to begin by year end as well as a combination trial to be conducted by Incyte in chronic GVHD patients with Jakafi in mid-2024. I will now turn the call over to Keith, to review our financial results. Keith?

我們期待啟動 axatilamab 的其他試驗，包括預計在年底開始的針對 135 名特發性肺纖維化患者的為期 26 週的隨機安慰劑對照 2 期試驗，以及由 Incyte 進行的慢性 GVHD 聯合試驗2024 年中期的Jakafi 患者。我現在將把電話轉給基思，以審查我們的財務表現。基思？

Thank you, Michael. Let me take a few minutes to discuss our financial results for the quarter ended September 30, 2023. Turning to slide 14, the results of our operations the third quarter of 2023 and the comparison to the prior year's quarter are included in our press release, so I won't repeat them in these remarks.

謝謝你，麥可。讓我花幾分鐘時間討論一下我們截至2023 年9 月30 日的季度的財務業績。轉向幻燈片14，我們的新聞稿中包含了2023 年第三季度的營運結果以及與上一年季度的比較，所以我不會在這些發言中重複它們。

Additional financial details are available in our third quarter 2023 report, which was filed earlier today and Form 10-Q. I'd like to point out that our net loss for the third quarter was $51.1 million or $0.73 per share compared to a net loss of $35.4 million was $0.58 per share for the comparable period last year.

更多財務細節請參閱我們今天早些時候提交的 2023 年第三季報告和 10-Q 表格。我想指出的是，我們第三季的淨虧損為 5,110 萬美元，即每股 0.73 美元，而去年同期的淨虧損為 3,540 萬美元，即每股 0.58 美元。

The difference in our net loss was driven largely by an increase in employee related expenses and professional fees within both SG&A and R&D, combined with increased clinical and manufacturing expenses. We ended the third quarter with $379.3 million in cash equivalents and short and long-term investments and $69.9 million shares and prefunded warrants outstanding.

我們淨虧損的差異主要是由於銷售、行政管理和研發內員工相關費用和專業費用的增加，以及臨床和製造費用的增加。截至第三季末，我們的現金等價物和短期和長期投資為 3.793 億美元，流通股和預融資認股權證為 6,990 萬美元。

Our balance sheet is expected to provide runway into the second half of 2025, which allows us to appropriately invest to maximize the value of our pipeline. And importantly, it also allows us to transition into a commercial stage organization in 2024.

我們的資產負債表預計將為 2025 年下半年提供跑道，這使我們能夠進行適當的投資，以最大限度地提高管道的價值。重要的是，它還使我們能夠在 2024 年過渡到商業階段組織。

Looking ahead, I'd like to provide financial guidance for the rest of this year. For the full year of 2023, the company expects research and development expenses to be $160 million to $165 million and total operating expenses to be $225 million to $230 million, both of which are inclusive of approximately $30 million of non-cash stock compensation expense. Note that this is a reduction from our prior guidance of $160 million to $175 million for R&D expense and $225 million to $240 million for total operating expenses. With that, let me now turn the call back over to Michael.

展望未來，我想為今年剩餘時間提供財務指導。 2023年全年，該公司預計研發費用為1.6億至1.65億美元，總營運費用為2.25億至2.3億美元，兩者均包括約3000萬美元的非現金股票補償費用。請注意，這比我們先前指導的研發費用 1.6 億美元減少到 1.75 億美元，總營運費用減少 2.25 億美元到 2.4 億美元。現在，讓我將電話轉回給麥可。

Thank you, Keith. Before we open the call for questions, I'd like to provide a summary of what was presented today in the near term. We remain laser focused on delivering quality data readouts, including the full AUGMENT-101 and AGAVE-201 data sets, as well as data from several other combination trials at the ASH annual meeting and our planned investor event by year end.

謝謝你，基斯。在我們開始提問之前，我想先對今天的近期內容進行總結。我們仍然專注於提供高品質的數據讀數，包括完整的 AUGMENT-101 和 AGAVE-201 數據集，以及 ASH 年會和我們計劃在年底舉行的投資者活動上的其他幾個組合試驗的數據。

We are excited to provide positive final Phase1results for revumenib treatment in relapse/refractory NPM1 patients further demonstrating its best in class profile in another important indication with high unmet medical need. Pivotal data from these trials will serve as the basis for potential US registrational filings, including an NDA submission in relapse/refractory KMT2A acute leukemia for revumenib and an insight initiated BLA submission in chronic GVHD for axatilimab by year end 2023.

我們很高興為復發/難治性 NPM1 患者提供 revumenib 治療的積極的最終 1 期結果，進一步證明其在另一個醫療需求未得到滿足的重要適應症中的最佳表現。這些試驗的關鍵數據將作為潛在的美國註冊申請的基礎，包括在 2023 年底之前提交 revumenib 用於治療復發/難治性 KMT2A 急性白血病的 NDA 以及針對 axatilimab 用於慢性 GVHD 的 Insight 啟動的 BLA 提交。

Both revumenib and axatilamab have significant market opportunities with the potential to gain -- quickly gained considerable market share and have a meaningful impact on the lives of underserved patients in each setting. In addition, we continue to explore ways to capture the maximum value of our current pipeline by expanding into opportunities beyond initial registration indications and in doing so aim to bring the encouraging clinical benefits of our lead candidates to even more patients in need.

revumenib 和 axatilamab 都擁有巨大的市場機會，並且有可能迅速獲得相當大的市場份額，並對每種情況下服務不足的患者的生活產生有意義的影響。此外，我們繼續探索如何透過擴展到初始註冊適應症以外的機會來獲取當前管道的最大價值，這樣做的目的是為更多有需要的患者帶來我們的主要候選人令人鼓舞的臨床益處。

It has been a transformational year for Syndax, and we expect to maintain this momentum in the coming months with a number of upcoming value-generating milestones that are laid out on Slide 15. I remain confident that we have the resources and expertise to execute on our goals and the strategic long-term vision that will enable our successful transition into a commercial stage biopharmaceutical organization.

對於Syndax 來說，今年是轉型的一年，我們預計在未來幾個月內保持這一勢頭，幻燈片15 中列出了許多即將到來的價值創造里程碑。我仍然相信，我們擁有執行這些任務所所需的資源和專業知識。我們的目標和策略長期願景將使我們能夠成功轉型為商業階段的生物製藥組織。

As always, I would like to extend my gratitude to the Syndax team, collaborators and most importantly, the patients trial sites and investigators involved with our clinical programs. Through your integral work, we are advancing our mission of realizing a future with -- which people with cancer live longer and better than ever before. I'd also like to thank our committed, long-term investors who continue to share in our vision and support us in building Syndax. With that, I would like to open the call for questions. Operator?

一如既往，我要向 Syndax 團隊、合作者表示感謝，最重要的是，向參與我們臨床計畫的病患試驗地點和研究人員表示感謝。透過你們的整體工作，我們正在推進我們的使命，實現一個未來——讓癌症患者比以往任何時候都活得更長、更好。我還要感謝我們忠誠的長期投資者，他們繼續分享我們的願景並支持我們建立 Syndax。至此，我想開始提問。操作員？

(Operator Instructions) Brad Canino, Stifel.

（操作員說明）Brad Canino，Stifel。

Hi, and thank you for the questions. Looking forward to ASH. I had a two-parter on the SAVE trial, actually the oral triplet where you had the abstract, it's first, when you speak to AML physicians, do you get the sense they're looking to use off-label combinations in the relapsed refractory setting. Because if we on the street that are anchored to monotherapy data, I guess what that might then mean about the ultimate opportunity in this treatment line in relapse/refractory as we think about efficacy percent to transplant maintenance, et cetera. And then I have a follow-up.

您好，謝謝您的提問。期待阿什。我在SAVE 試驗中有一個兩人參與的試驗，實際上是口服三聯體，您有摘要，首先，當您與AML 醫生交談時，您是否感覺到他們正在尋求在復發難治性患者中使用標籤外組合環境。因為如果我們在街上以單一療法數據為基礎，我猜當我們考慮移植維持的療效百分比等時，這可能意味著復發/難治性治療線的最終機會。然後我有一個後續行動。

Brad, thanks for the question. I'm going to ask Neil to make a comment.

布拉德，謝謝你的提問。我要請尼爾發表評論。

Yeah, look, thanks for the question. Obviously, this is a preliminary dose ranging and there's more work to be done. We see the value in the data that Dr. Issa is generating a couple of different ways. So first of all, if the demonstration of the combinability revumenib with venetoclax hypomethylating agents, I think it's very important. And the study is ongoing with revumenib administered at full dose in DL1 as it mentioned in the abstract.

是的，看，謝謝你的提問。顯然，這是初步的劑量範圍，還有更多的工作要做。我們看到了伊薩博士透過幾種不同方式產生的數據的價值。所以首先，如果證明revumenib與venetoclax低甲基化藥物的組合性，我認為這是非常重要的。如摘要中所提到的，研究正在進行中，以全劑量 DL1 給藥 revumenib。

The other thing to bear in mind is that historically, if you look at this population, they're quite heavily pretreated. Most of them have actually failed, venetoclax and hypomethylating agent. And one would expect response rate therefore to venetoclax plus an HMA to be quite low, actually probably less than 10%. And here we're seeing a much, much higher response rate, 28% CH/CRh rate. So this is actually incremental progress, albeit based on early data, incremental progress for those patients.

另一件需要記住的事情是，從歷史上看，如果你觀察這個群體，你會發現他們受到了相當嚴重的預處理。其中大多數實際上都失敗了，venetoclax和低甲基化劑。因此，人們預期 Venetoclax 加 HMA 的反應率會相當低，實際上可能低於 10%。在這裡，我們看到了非常非常高的回覆率，CH/CRh 率為 28%。因此，這實際上是漸進式的進展，儘管是基於早期數據，是這些患者的漸進式進展。

Great. And then -- yeah, on the safety for the regimen, I guess if it's higher and more prolonged myelosuppression than would be expected from the component? And how are you thinking about this, too? As we think about the frontline [Venza] combo, that might be a different patient population in terms of and how myelosuppression might affect them. Thank you.

偉大的。然後——是的，關於該方案的安全性，我想它的骨髓抑製作用是否比該成分預期的更高、更持久？您也如何看待這個問題？當我們考慮一線 [Venza] 組合時，就骨髓抑制可能如何影響他們而言，這可能是不同的患者群體。謝謝。

Yeah, thanks for the question. Just continuing on as the authors themselves concluded that the safety profile is what you would expect from Van and the hypomethylating agents. So there is you know the triplet, you can call it a triplet. It appears to be extremely well tolerated, right, for pre-treated patient.

是的，謝謝你的提問。繼續，因為作者自己得出的結論是，Van 和低甲基化劑的安全性正是您所期望的。所以你知道三元組，你可以稱它為三元組。對於接受過治療的患者來說，它的耐受性似乎非常好。

And just going to your point about what does that mean as we advance in combinations in earlier stage patients, I think it's signal and good thing, right. Because if heavily pretreated patients can actually tolerate the combination the it is highly likely that less heavily pretreated patients will also tolerate the combination well.

就你的觀點來說，當我們在早期患者的聯合療法中取得進展時，這意味著什麼，我認為這是一個信號，也是一件好事，對吧。因為如果經過大量預處理的患者實際上能夠耐受該組合，那麼預處理程度較低的患者很可能也能很好地耐受該組合。

So, we are encouraged, as I mentioned during my prepared remarks. Overall, when you look at the data that are evolving some the data that we've presented today. We are highly encouraged for the opportunity to advance revumenib into early-stage combination therapies.

因此，正如我在準備好的發言中提到的那樣，我們感到鼓舞。總體而言，當您查看正在演變的數據時，您會發現我們今天提供的一些數據。我們對有機會將 revumenib 推進早期聯合療法感到非常鼓舞。

Thanks Brad,

謝謝布拉德，

Anupam Rama, JP Morgan.

阿努帕姆‧拉瑪，摩根大通。

Yeah, this is actually Malcolm Kuno on for Anupam and thank you for taking the questions. What additional data are you planning to present at ASH on AUGMENT-101 KMT2A versus what we already know from the topline data? Thank you.

是的，我是馬爾科姆·庫諾 (Malcolm Kuno) 在 Anupam 上發言，感謝您提出問題。與我們從頂線資料中已知的資料相比，您計劃在 AUGMENT-101 KMT2A 的 ASH 上展示哪些額外資料？謝謝。

Yeah, Malcolm thank you for the question. So as we had previously said and I think we said remarks, obviously, we have presented top line in recent days and we will be at ASH, we have an abstract that came out today that explains that we will have a presentation at ASH add our investor event.

是的，馬爾科姆，謝謝你的提問。正如我們之前所說，我想我們也說過這樣的話，顯然，我們最近幾天已經提出了頂線，我們將在ASH 上，我們今天發布了一份摘要，說明我們將在ASH 上進行演示，新增我們的投資者活動。

I think the data that has been top lined is the data cut, but we will have additional analyses that I think, go into more specific details around that particular data cut. Whether it is and then not to speculate specifically around what we are going to present, but I think l there are some important analyses that will allow people to get even deeper feel for what we presented previously. Si stay tunes, but we will have obviously more data at ASH and then again at our Investor Day.

我認為最上面的數據是數據切割，但我認為我們將進行額外的分析，圍繞該特定數據切割進行更具體的細節。不管是不是，然後不要具體推測我們將要呈現的內容，但我認為有一些重要的分析將使人們對我們之前呈現的內容有更深入的感受。請繼續關注，但我們顯然會在 ASH 上獲得更多數據，然後在投資者日上再次獲得。

Excellent. Thank you.

出色的。謝謝。

Chris Shibutani, Goldman Sachs.

克里斯·澀谷，高盛。

Hi, good afternoon. Thank you so much for taking our questions. This is Charlie on for Chris. Just to kind of follow up on the last question. I'm wondering, do you have the same data cut for the AUGMENT-101 presentation at ASH? So it sounds like we're going to assume the same 57 patients that we had for the top line results. Just wondering what's the rolling submission with the FDA currently are they going to be looking for those additional 37 patients that are after that data cut? Thank you.

嗨，下午好。非常感謝您接受我們的提問。這是查理為克里斯代言的。只是為了跟進最後一個問題。我想知道，你們在 ASH 上的 AUGMENT-101 演示中是否有相同的資料切割？因此，聽起來我們將假設與我們的頂線結果相同的 57 名患者。只是想知道目前 FDA 滾動提交的文件是什麼，他們是否會尋找數據削減後的另外 37 名患者？謝謝。

Yeah, Charlie thank you. You're correct, it is the same data cut at ASH. what actually mean we are very focused on getting our NDA filed. And as you noted, under Arthur, we have a and pretty rigorous and a short timeline to complete the filing by year end. So it is a rolling submission.

是的，查理，謝謝你。你是對的，這與 ASH 中的資料切割相同。這實際上意味著我們非常專注於提交 NDA。正如您所指出的，在阿瑟的領導下，我們有一個相當嚴格且較短的時間表來在年底前完成備案。所以這是一個滾動提交。

The agency has very specifically around according to our plan, which is, again efficacy on the 57 patient with safety on the overall 94, which will be outlined when we top line data and confirmed through our pre-IND meeting at our [arothor] process. So the data will be -- they see all the data but there is no new data cut required from an efficacy standpoint and safety obviously will be submitted as such. So that is a way to look at it.

該機構根據我們的計劃制定了非常具體的計劃，即再次對57 名患者有效，對總體94 名患者安全，這將在我們頂線數據時概述，並通過我們的[arothor] 流程中的IND 前會議確認。因此，數據將是——他們看到了所有數據，但從功效的角度來看，不需要削減新的數據，安全性顯然將如此提交。所以這是一種看待它的方式。

Okay, great. Thank you so much.

好的，太好了。太感謝了。

(inaudible)

（聽不清楚）

Hi sir. This is Ashok Kumar on for [Yigal]. Thanks for taking my question. I just had one on the on the post-transplant setting data you have shared. It seems like you are getting very long durability in terms of patients staying on drug for long periods of time post-transplant, which is great. I guess how are you thinking about the commercial opportunity sort of on average in terms of duration treatment in the context of the post transport? Thanks.

你好，先生。這是 [Yigal] 的 Ashok Kumar。感謝您提出我的問題。我剛剛收到一份關於您分享的移植後設定數據的資訊。就患者在移植後長時間服用藥物而言，您似乎獲得了非常長的持久性，這很棒。我想您如何看待郵政運輸背景下平均持續時間處理的商業機會？謝謝。

Yeah. Thanks for the question. And I going to turn over the Anjali to answer this.

是的。謝謝你的提問。我將翻開 Anjali 來回答這個問題。

Thanks for the question. So we have been thinking about and speak into a number of physicians about how they want to use revumenib based on the data we are generating. And they see that there is an opportunity to treat patients in the post-transplant maintenance setting. The drug is able to get patients to deep durable responses, and they see no downside for continuing them on therapy after transplant.

謝謝你的提問。因此，我們一直在考慮並與許多醫生交談，以了解他們希望根據我們產生的數據如何使用瑞維美尼。他們發現有機會在移植後維持環境中治療患者。該藥物能夠使患者產生深度持久的反應，並且他們認為移植後繼續治療沒有任何負面影響。

And the goal, I think would be to keep them on as long as possible, but there is a standard today is assumed to be close to Two years. Obviously not every patient will achieve that and not every patient is able to succesfully receive a transplant. So we estimate that conservatively that duration on average will be close to 18 months.

我認為目標是盡可能長時間地保留它們，但今天有一個標準，假設接近兩年。顯然，並不是每個患者都能實現這一點，也不是每個患者都能成功接受移植。因此，我們保守估計平均持續時間將接近 18 個月。

Okay. That's very helpful. And just a conceptual question on the same topic. What's the decision making for the physician behind choosing the women to end treatment in the post-transplant setting? Is it disease progression or is there a point at which they kind of determine the benefit, it may be a lowering overtime I would say the risk of disease progression. Thanks.

好的。這非常有幫助。只是關於同一主題的概念性問題。選擇女性結束移植後治療的醫師有何決策？是疾病進展還是在某個點上他們確定了益處，我想說的是，這可能是降低疾病進展的風險。謝謝。

Yeah. Good question. SO Neil, why don't you comment on it?

是的。好問題。那麼尼爾，你為什麼不對此發表評論呢？

Yeah. Thanks for the question. As you noted, we're seeing patients actually remaining on the drug for a very protracted periods of time on. And that says to us -- that it speaks to the tolerability profile of the drug, which has consistently been very good. The feedback we've obviously talked to investigators and other physicians about this, and they're very keen when we speak with them.

是的。謝謝你的提問。正如您所指出的，我們看到患者實際上在很長一段時間內繼續服用該藥物。這對我們來說——它說明了該藥物的耐受性，一直都非常好。我們顯然已經與研究人員和其他醫生就此進行了交談，當我們與他們交談時，他們非常熱衷。

First of all, they wanted this option. Just to remind you, they wanted this option in the study. It wasn't there in the earlier part of the study, and we included it in Phase 2 at the request of the investigators. So that's one point. The other point is, as we talk to them now they see themselves, keeping patients on for a protracted period of time, right?

首先，他們想要這個選擇。只是提醒您，他們希望在研究中使用這個選項。它在研究的早期部分中並不存在，我們應研究人員的要求將其納入第二階段。這是一點。另一點是，當我們現在與他們交談時，他們看到自己讓病人長期堅持治療，對嗎？

So they talk about two years, right, for instance. But in fact, there's evidence to suggest that patients could stay on longer than that as well. So I don't I think as long as patients -- and remember that these patients are extremely high-risk, very heavily pretreated. The KMT2A cohort that we've presented that we reiterated today very heavily pretreated. And therefore, there's no way that physicians are looking at it is why take the risk the patients are.

所以他們談論的是兩年，對吧，例如。但事實上，有證據顯示患者的治療時間也可以比這更長。所以我認為只要患者——並記住這些患者風險極高，接受過嚴格的預處理。我們今天重申的 KMT2A 隊列經過了嚴格的預處理。因此，醫生不可能考慮為什麼要讓病人冒這個風險。

The drug is getting the patients into response, getting the patients to transplant, the well-tolerated and therefore, the patients can go back on it after transplant. Why not just keep the patients on the drug? That's the feedback that we're getting.

該藥物使患者產生反應，使患者進行移植，耐受性良好，因此患者可以在移植後繼續使用。為什麼不讓病人繼續用藥？這就是我們收到的回饋。

Got it. Very helpful. Thanks very much.

知道了。很有幫助。非常感謝。

You're welcome.

不客氣。

Thank you.

謝謝。

Phil Nadeau, TD Cowen.

菲爾·納多，TD·考恩。

Good afternoon. A couple of questions from us. First, congrats on the 36% CR/CRh rate with three additional patients in terms of the pivotal trial, NPM1, for revumenib, can you discuss in a bit more detail. What's the implications of the 16% of enrollment coming out of Israel? Is it that the chance of patients will be lost to follow up or the data will be lost? How does that impact the timelines and the number of patients that you need to enroll?

午安.我們有幾個問題。首先，恭喜 Revumenib 的關鍵試驗 NPM1 中另外三名患者獲得了 36% 的 CR/CRh 率，您能更詳細地討論一下嗎？ 16% 的入學人數來自以色列，這代表什麼？是否會導致患者失去追蹤機會或資料遺失？這對您需要招募的時間表和患者數量有何影響？

Yeah. Thanks for the question Phil. Look I think it's an unfortunate set of events going there. And yet our trial sites are still up and running in Israel where data is centralized. So we have obviously good control over the data, not the issue and the implications we think are hard to -- little bit hard to predict, but we have a lot of other sites and we're doing quite well with enrollment elsewhere.

是的。感謝菲爾提出問題。聽著，我認為那裡發生了一系列不幸的事件。然而，我們的試驗站點仍在資料集中的以色列正常運作。因此，我們顯然對數據有很好的控制，而不是我們認為很難預測的問題和影響，但我們有很多其他網站，而且我們在其他地方的註冊方面做得很好。

And so I think that's something we will -- we feel very confident we can pick up and complete the trial by the end of the first quarter or very early in the second quarter. So it's something that's a little bit unfortunate. But, as I said, or Neil said in the remarks, these are typically high enrolling sites, and it was just a little bit unfortunate, but we feel very confident that we'll be able to get it done on time.

所以我認為這是我們將要做的事情 - 我們非常有信心能夠在第一季末或第二季初開始並完成試驗。所以這是一件有點不幸的事。但是，正如我所說，或者尼爾在評論中所說，這些通常都是高註冊網站，這只是有點不幸，但我們非常有信心能夠按時完成。

Got it. That's helpful. And then a follow-up question on the SAFE trial. From the abstract said that enrollment, continued in SAFE and additional on it or updated data will be presented at the meeting. What can we expect in terms of patients at dose level one it at ASH? I think there were two in the abstract. Would there be another four to ASH or could dose level one enrolled beyond the six that were enrolled at dose level zero?

知道了。這很有幫助。然後是關於 SAFE 審判的後續問題。摘要稱，外管局的註冊、繼續和補充或更新資料將在會議上提交。對於 ASH 中劑量為一的患者，我們可以期待什麼？我認為抽像地說有兩個。是否還會有另外 4 位 ASH 患者，或是否可以在 0 劑量等級登記的 6 個劑量等級之外登記 1 劑量等級？

Yes, Phil, thanks for the question. It's a little bit hard to answer at this point. I think they are continuing to enroll at that dose level. As you know, there are only a few that were enrolled so far. The results have been quite strong and striking. So they're looking forward to expanding that to additional patients and that will be obviously presented at ASH in the in the presentation. But I can't give you specific numbers on how many patients will be expanded to. I just don't have that detail.

是的，菲爾，謝謝你的提問。現在有點難回答。我認為他們會繼續以該劑量水平註冊。如您所知，到目前為止，只有少數人被錄取。結果非常強勁且引人注目。因此，他們期待將其擴展到更多患者，這將在 ASH 的演示中得到明顯體現。但我無法向您提供有關將擴大到多少患者的具體數字。我只是沒有那個細節。

Fair enough. Thanks for taking our questions.

很公平。感謝您回答我們的問題。

Yeah, thank you so much.

是的，非常感謝。

Jason Zemansky, Bank of America.

傑森澤曼斯基，美國銀行。

Hi, this is Alex for Jason Zemansky. Thank you for taking my question. What sort of data do you think is necessary before the community can start to feel confident about revumenib common ability profile? What do we need to see in terms of safety and efficacy? Thank you.

大家好，我是傑森·澤曼斯基的亞歷克斯。感謝您回答我的問題。您認為在社群開始對 revumenib 通用能力概況充滿信心之前需要什麼樣的資料？在安全性和有效性方面我們需要看到什麼？謝謝。

Yeah. Thanks for the question. But look I think the data we generated to date, both as a monotherapy and now in NPM1 and for KMT2A really is a good source or I should say, underpins well, what we would expect to see is a contribution of components, right? When you think about combining drugs such as with [cancer] and with chemotherapy.

是的。謝謝你的提問。但我認為我們迄今為止產生的數據，無論是作為單一療法，還是現在在NPM1 和KMT2A 中，確實是一個很好的來源，或者我應該說，很好地支撐了，我們期望看到的是成分的貢獻，對嗎？當您考慮將藥物與[癌症]和化療結合使用時。

So we feel very confident that we have best in class monotherapy data and that's a good starting point with combinations of first things first and Neil made comments about this. You need to be able to combine these drugs safely and effectively, but full dose monotherapy dose getting to those levels in a combination is extremely important.

因此，我們非常有信心，我們擁有一流的單藥治療數據，這是一個很好的起點，首先要結合第一件事，尼爾對此發表了評論。您需要能夠安全有效地組合這些藥物，但在組合中達到這些水平的全劑量單藥治療劑量極為重要。

And the SAVE information -- SAVE trial information that came out today really supports that. We will have data at ASH for the BEAT- AML trial, which is frontline patients. The SAVE trial were that's in relapse/refractory patients.

今天發布的 SAVE 資訊——SAVE 試用資訊確實支持了這一點。我們將在 ASH 獲得 BEAT-AML 試驗的數據，該試驗是第一線患者。 SAVE 試驗是在復發/難治性患者中進行的。

But BEAT-AML trial is newly diagnosed patients and the opportunity to not only safely dose patients, but dose them at the full monotherapy dose as well as drive response rates as you'd hope to be as good or better than what they see in the doublet and that's what we're looking for.

但BEAT-AML 試驗針對的是新診斷的患者，不僅有機會安全地給患者用藥，而且可以按單藥治療的全部劑量給他們用藥，並提高緩解率，正如您希望的那樣好或比他們在試驗中看到的更好。雙合體，這就是我們正在尋找的。

And I would also say MRD negativity is a big driver of physician choice and how they think about treating their patients. We've been able to show deep durable responses signal by MRD negativity and that something we'll look at in these combinations as well, where patients are not necessarily getting to full MRD negative status. So there's those are the types of things that we'll look for. And we expect to have meaningful data for the end of the year to kind of elucidate all that.

我還想說，MRD 陰性是醫生選擇以及他們如何看待治療患者的一個重要驅動因素。我們已經能夠透過 MRD 陰性顯示出深層持久的反應訊號，我們也會在這些組合中觀察到一些東西，其中患者不一定會達到完全 MRD 陰性狀態。我們要尋找的就是這些類型的東西。我們期望在今年年底獲得有意義的數據來闡明這一切。

Peter Lawson, Barclays.

彼得·勞森，巴克萊銀行。

Yeah. Thanks for the update for the MRD negative patients. Do you have enough data now to filed for breakthrough designation and we can update this data at the Investor Day and then are patients going to transplant and could that cause a downdraft in the CR CRh rate in a pivotal trial? Thank you.

是的。感謝您對 MRD 陰性患者的更新。您現在是否有足夠的數據來申請突破性指定，我們可以在投資者日更新這些數據，然後患者是否要進行移植，這是否會導致關鍵試驗中 CR CRh 率下降？謝謝。

Yes, Peter, thank you. So I think you had a couple of different questions here. One was taking from its reverse order here. So could patients go on to -- do we see patients go to transplant? I think the answer AMPM1 patient, I think the answer is obviously, yes. You see that in the swimmer's lane that we have on our slides as well as, as we have mentioned in the remarks of patients are going to transplant, three of the patients of the 14 went to transplant, and many of them are staying on treatment for and also in remission.

是的，彼得，謝謝你。所以我認為您在這裡有幾個不同的問題。其中之一是從這裡的相反順序開始的。那麼患者是否可以繼續下去——我們是否看到患者接受移植？我認為AMPM1患者的答案，我認為答案顯然是肯定的。你看，在我們幻燈片上的泳道上，正如我們在即將接受移植的患者的評論中提到的，14 名患者中有 3 名接受了移植，其中許多人仍在接受治療也處於緩解期。

So I think that is an important fact pattern. Also important to note what we saw in the Phase 1 sorry in the pivotal trial for KMT2A. We and Neil mentioned in his remarks, the number of patients who didn't reach complete count recovery, so didn't reach CR/CRh's best response. And we're taking to transplant very quickly that actually ended up penalizing us a bit on the CR/CRh rate.

所以我認為這是一個重要的事實模式。同樣重要的是要注意我們在 KMT2A 關鍵試驗的第一階段中看到的情況。我們和Neil在演講中提到，有多少患者沒有達到計數完全恢復，因此沒有達到CR/CRh的最佳反應。我們的移植速度非常快，這實際上最終導致我們的 CR/CRh 率受到了一些影響。

As the owner marked, it could have been as high as 37% if all those patients had converted and maybe didn't go to transplant as quickly (technical difficulty) lower in terms of taking patients to transplant. So these patients are also not necessarily as fit as what you see with KMT2A younger patients.

正如所有者所指出的，如果所有這些患者都已轉變並且可能不那麼快（技術難度）較低地接受患者進行移植，那麼它可能高達 37%。因此，這些患者也不一定像 KMT2A 年輕患者那樣健康。

So we're actually not seeing, if you look at the data, we're not seeing patients at CRP or incomplete hematological recovery points. And so what you're seeing is all of our patients are CR/CRh and MRD-negative and some of them are going to transplant. So it just tells you the time course probably has an impact in terms of reaching your full potential for CR/CRh as an NPM1 patient. So we don't think actually that's going to be meaningfully impactful in the Phase 2.

所以我們實際上沒有看到，如果你看一下數據，我們沒有看到處於 CRP 或不完全血液學恢復點的患者。所以你看到的是我們所有的病人都是 CR/CRh 和 MRD 陰性，其中一些病人將進行移植。因此，它只是告訴您時間進程可能會對您作為 NPM1 患者充分發揮 CR/CRh 潛力產生影響。因此，我們認為實際上這不會對第二階段產生有意義的影響。

In fact, we see it as the opposite. We see that the CR/CRh could actually be more reminiscent of what we're seeing now, which is in the mid-30s or higher on NPM1 we'll have to see what the data bears out. But we don't think that the same treatment paradigm in terms of the speed at which physicians take their patients to transplant is going to penalize in the same way, it did for us on the CR/CRh and KMT2A.

事實上，我們的看法恰恰相反。我們發現 CR/CRh 實際上可能更讓人想起我們現在所看到的情況，即 NPM1 上的 30 多歲或更高，我們必須看看數據證實了什麼。但我們認為，就醫生將患者移植的速度而言，相同的治療模式不會像我們在 CR/CRh 和 KMT2A 上那樣受到相同的懲罰。

We will have an update. This is the data. We may have some more to say at our investor event on NPM1, but this is the data that we have in hand. And so we wanted to get at obviously out to you today, but we haven't really bottomed out on what else we would analyze for our R&D Day or Investor Day for in and around ASH. And maybe there was another question on obesity.

我們將會有更新。這是數據。在 NPM1 的投資者活動上，我們可能還有更多要說的，但這是我們手頭上的數據。因此，我們今天顯然想向您傳達這一訊息，但我們還沒有真正了解我們將在 ASH 內外的研發日或投資者日分析什麼。也許還有一個關於肥胖的問題。

Right exactly.

完全正確。

Right Peter. So look, I think we've said in the past, you need approximately 20 to 30 patients at the RP2D to file for breakthrough therapy designation. As you see here, this is 14 patients at the break at the RP2D. So right now, we don't expect that we would be able to make that application. Obviously, that's something that is open to us at some point in time relative to our pivotal data, which is obviously coming. So that's it. Thank you.

對了彼得。所以，我想我們過去說過，需要 RP2D 大約 20 到 30 名患者來申請突破性治療指定。正如您在此處看到的，這是 RP2D 休息時的 14 名患者。所以現在，我們預計我們無法提出該申請。顯然，這是在某個時間點向我們開放的與我們的關鍵數據相關的東西，這顯然即將到來。就是這樣了。謝謝。

Perfect.

完美的。

Thanks Peter.

謝謝彼得。

Michael Schmidt, Guggenheim.

邁克爾·施密特，古根漢。

Hey guys, good afternoon. Thanks for taking my questions. In the NPM1 cohort how many patients had overlapping co-mutations, other genetic alterations and potentially have had received other targeted agents prior to resuming revumenib and how do you expect that dynamic to play out in that pivotal cohort and ultimately on the market? Thank you so much.

嘿夥計們，下午好。感謝您回答我的問題。在NPM1 隊列中，有多少患者存在重疊共突變、其他基因改變，並且在恢復revumenib 之前可能已經接受過其他標靶藥物？您預計這種動態將如何在該關鍵隊列中發揮作用並最終在市場上發揮作用？太感謝了。

Yes, Michael, thanks for the question. So we didn't break out that data in the swimmer�s lane. But I'll tell you, as you as you noticed in the -- we did say that a lot of obviously -- a lot of prior therapy for these patients in terms of co-mutations, I think the vast majority, if not all, were co-mutated. So there were obviously there's variations on the theme of what we saw, but we didn't break that out. But I think suffice to say, we had most patients were co-mutated. Yeah, it's obviously representative of what you would think.

是的，邁克爾，謝謝你的提問。所以我們沒有在泳道上公佈這些數據。但我會告訴你，正如你在我們確實說過的那樣，在共同突變方面對這些患者進行了很多先前的治療，我認為絕大多數（如果不是全部） ，共同突變。因此，我們所看到的主題顯然存在差異，但我們沒有將其打破。但我認為足以說，我們的大多數患者都是共同突變的。是的，這顯然代表了你的想法。

Okay. And in order to how does that affect potential sequencing of therapies? Should the data be replicated in your pivotals study, if approved, in your opinion?

好的。這對潛在的治療順序有何影響？您認為，如果獲得批准，這些數據是否應該在您的關鍵研究中複製？

Yes, I think what you're getting at is whether or not physicians will look at targeting these specific mutations for treatment. And obviously, the paradigm for NPM1, at least in the unfit population or the fit population, they get chemo, or they get Ven/Aza upfront. And then physicians look to target their mutations with either a FLT3 or an IDH inhibitor.

是的，我認為你要問的是醫生是否會考慮針對這些特定突變進行治療。顯然，NPM1 的範例，至少在不健康人群或健康人群中，他們接受化療，或預先接受 Ven/Aza。然後醫生希望用 FLT3 或 IDH 抑制劑來靶向突變。

And we do expect that if these patients have those mutations, that's what's going to happen in the real world and in our trial as well. So that's what ends up resulting and I think the remarks that I made suggest this that the physicians will be reaching for second or third line revumenib after they've taken action against, obviously frontline and then they're going after their targeted mutation to the extent they have one.

我們確實預計，如果這些患者有這些突變，那麼現實世界和我們的試驗中也會發生這種情況。這就是最終的結果，我認為我所說的言論表明，醫生們在採取行動對抗顯然是前線的藥物後，將尋求二線或三線瑞維美尼，然後他們將針對目標突變進行治療他們有一個程度。

So I think the data that we presented today shows that right? It shows that patients do extremely well treat in, call it, the third-line fourth line setting on our drug. And as they progress and get into very, very late lines of therapy, which we've had some patients also like that and they don't do as well. So yes, I think the targeting of these mutations will likely come before revumenib.

所以我認為我們今天提供的數據表明了這一點，對嗎？它表明患者在我們的藥物的三線四線設置中得到了非常好的治療。隨著他們的進展並進入非常非常晚期的治療，我們有一些患者也喜歡這樣，但他們做得不好。所以是的，我認為這些突變的靶向可能會在瑞美尼之前出現。

Thanks so much.

非常感謝。

Thank you.

謝謝。

Kalpit Patel at B. Riley.

B. Riley 的卡爾皮特·帕特爾 (Kalpit Patel)。

Yeah, hey. Good afternoon and congrats on all the updates today. Maybe a couple of more questions related to the maintenance use of revumenib. Now that you have all the post-transplant data here. How are you seeing the median duration of treatment for revumenib between the KMT2A populations and the NPM1 populations? Do you expect them to be very similar to each other?

是的，嘿。下午好，祝賀今天的所有更新。也許還有一些與瑞維美尼維持使用相關的問題。現在您已經擁有所有移植後資料。您如何看待 KMT2A 族群和 NPM1 族群之間的 revumenib 治療中位數持續時間？你認為他們彼此非常相似嗎？

Yeah, thank you for the question. Yeah, I think we do think it's going to be very similar. It's interesting how the data converges a bit, right? So you have patients in the KMT2A population that a great percentage go get a response high -- overall response rate get taken to transplant and put back on drug and stay on drug do very, very well.

是的，謝謝你的提問。是的，我認為我們確實認為它會非常相似。數據如何收斂一點很有趣，對吧？因此，KMT2A 人群中的患者中有很大一部分獲得了高反應——移植、重新用藥和繼續用藥的總體反應率非常非常好。

The speed at which they get a best response first and best response and then move to transplant is noteworthy in KMT2A. It's a bit slower with NPM1, which probably allows their accounts to recover, as I mentioned earlier. But the paradigm is seems to be similar, at least in relapsed refractory disease where physicians are interested in putting them back on once you get to a CR, you take them to transplant and you put them back on drug.

在 KMT2A 中，他們首先獲得最佳反應以及最佳反應然後進行移植的速度值得注意。正如我之前提到的，NPM1 的速度有點慢，這可能允許他們的帳戶恢復。但模式似乎是相似的，至少在復發性難治性疾病中，醫生有興趣在達到 CR 後將它們重新放回，帶它們進行移植，然後放回藥物。

I think that's also new and it is a new paradigm, but it actually a very positive back pattern for the drug in terms of the ability to treat patients for a long time and keep them in remission. So we're actually very encouraged by what we're seeing both by the from the efficacy standpoint and the tolerability safety standpoint to allow this to be the new paradigm. So it's quite interesting how it turned out to be pretty similar.

我認為這也是新的，這是一個新的範式，但就長期治療患者並使他們保持緩解的能力而言，它實際上是該藥物非常積極的背部模式。因此，從功效的角度和耐受性安全的角度來看，我們實際上對我們所看到的感到非常鼓舞，使其成為新的範例。所以很有趣的是它是如何變得非常相似的。

Okay. And then it's nice to see the additional responses in the NPM1 patient population. I'm just curious if you have any more NPM1 patients after that, I believe July cut off in that data in that Phase 1?

好的。然後很高興看到 NPM1 患者群體中的額外反應。我只是好奇此後是否還有更多 NPM1 患者，我相信 7 月第一階段的數據就被切斷了？

Yeah, thanks for the follow up. We do not. That is -- this is the final data in terms of the patients that's all we have. We were looking to complete the pharmacokinetic work in the Phase 1, and we had talked about that in the past and this was these are the remaining patients to accomplish that.

是的，感謝您的跟進。我們不。也就是說，這是我們所擁有的所有患者的最終數據。我們希望完成第一階段的藥物動力學工作，我們過去曾討論過這一點，而這些是完成這一目標的剩餘患者。

Okay, perfect. Thank you.

好的，完美。謝謝。

Thank you.

謝謝。

Justin Zelin, BTIG.

賈斯汀·澤林，BTIG。

Hi. Thanks for taking my question and congrats on the progress here. Maybe a question just on the SAVE AML study, I think the abstract show there wasn't much differentiation syndrome seen here. Can you comment on whether you'd expect the differentiation syndrome to be reduced in the combination setting moving forward? Thank you.

你好。感謝您提出我的問題並祝賀這裡的進展。也許只是關於 SAVE AML 研究的問題，我認為摘要顯示這裡沒有看到太多分化綜合症。您能否評論一下您是否期望在未來的聯合治療中減少分化綜合症？謝謝。

Yeah. Thanks, Justin. The answer is yes. I mean, the data, as we've discussed today, are highly encouraging. And I think that clearly the combination with Venza, of revumenib with Venza and the hypomethylating agent is extremely well tolerated. So there's no reasons to suspect that we would see a different pattern as we advance, for instance, as we advance a combination of and sennhypomethylating agent into earlier lines therapy. So, I think it's both expected and gratifying to see.

是的。謝謝，賈斯汀。答案是肯定的。我的意思是，正如我們今天討論的那樣，這些數據非常令人鼓舞。我認為很明顯，revumenib 與 Venza 的組合以及低甲基化劑的耐受性非常好。因此，沒有理由懷疑隨著我們的進展，我們會看到不同的模式，例如，當我們將 和 低甲基化藥物的組合推進到早期的一線治療時。所以，我認為這是既令人期待又令人欣慰的。

Great. Thanks. And congrats again on the plenary for axatilimab. Anything additional we should look out for at ASH of beyond what we saw at the top line.

偉大的。謝謝。再次恭喜 axatilimab 召開全體會議。除了我們在頂線看到的內容之外，我們還應該在 ASH 中關注任何其他內容。

Justin, I think yes, thank you. We obviously have the plenary at for axatilimab, which is very exciting. I think , we had five abstracts out today. So a lot of information saved as we talked about, but also some of the combinations, and so yeah just a lot of interesting information coming your way and obviously, we'll have lots say at our event at ASH as well. So I'm looking forward to seeing everybody there.

賈斯汀，我想是的，謝謝。顯然，我們召開了關於 axatilimab 的全體會議，這非常令人興奮。我想，我們今天有五篇摘要。正如我們所討論的，我們保存了很多信息，還有一些組合，所以是的，您會收到很多有趣的信息，顯然，我們在 ASH 的活動中也會有很多發言權。所以我很期待在那裡見到大家。

Great. Thanks for taking my questions.

偉大的。感謝您回答我的問題。

Yeah. Thank you.

是的。謝謝。

George Farmer, Scotiabank.

豐業銀行的喬治法默。

Hi, good afternoon. Thanks for taking my question. Neil, you mentioned that the 6.4-month DOR in the AUGMENT-1 trial could get better. I'm wondering if it is possible it could get worse. We haven't seen any capital minor curve. So just wondering what your thoughts are there? And then also in the SAVE trial and that alluded to a previous question, about the myelosuppression. Wondering if those patients got any growth factor support and if growth factors were affected, perhaps maybe revumenib had an impact on a recovery or anything like that, if you could comment on. Thanks.

嗨，下午好。感謝您提出我的問題。 Neil，您提到 AUGMENT-1 試驗中 6.4 個月的 DOR 可能會變得更好。我想知道情況是否有可能變得更糟。我們還沒有看到任何資本小曲線。所以只是想知道你的想法是什麼？然後也在 SAVE 試驗中，這提到了先前的問題，關於骨髓抑制。想知道這些患者是否得到了任何生長因子支持，以及生長因子是否受到影響，也許瑞維美尼對康復或類似的事情有影響，如果您可以發表評論。謝謝。

Sure. Thanks for the question. So with respect to the first question, we have modeled it out in our there's been a noise in the line. But with respect you know our expectation is that the median DOR can extend over time with additional follow-up right. So we've modeled that out and running various -- sorry, I'm blanking on the word.

當然。謝謝你的提問。因此，關於第一個問題，我們已經在線路中有雜訊中對其進行了建模。但請恕我直言，我們的期望是，隨著時間的推移，DOR 中位數可以隨著時間的推移而延長，並有額外的後續權利。所以我們對此進行了建模並運行了各種 - 抱歉，我對這個詞一片空白。

But statisticians have modeled out looking very various different our scenarios and we see multiple different scenarios under which the median DOR can extend over time. To the second point not to the best of my knowledge with respect to stem cells or with respect to growth factor support -- you know that's not understanding.

但統計學家已經模擬出了各種不同的場景，我們看到了多種不同的場景，在這些場景下，DOR 中位數可以隨著時間的推移而延長。對於第二點，據我所知，關於幹細胞或生長因子支持，你知道這不是理解。

Okay. Great. And then one more, if I could on axatilimab. The IPF study can you just speak kind of high-level about the design of that trial?

好的。偉大的。如果可以的話，然後再服用 axatilimab。 IPF 研究您能簡單介紹一下該試驗的設計嗎？

Sure. I'll take that. As Michael said in his remarks, it's a randomized Phase 2. It's randomized 135 patients as a target sample size randomized two to one active axatilimab to placebo on a background of best supportive care. So very succinctly, that is the study design. We think that it's an efficient way to address the proof-of-concept question.

當然。我會接受的。正如Michael 在他的演講中所說，這是一個隨機的第2 階段。它以135 名患者為隨機目標樣本量，在最佳支持護理的背景下，隨機將兩對一活性axatilimab 與安慰劑進行比較。非常簡潔，這就是研究設計。我們認為這是解決概念驗證問題的有效方法。

Is that a six-month study? 52 weeks?

這是六個月的研究嗎？ 52週？

26 weeks, that's right. 26-week primary endpoint analysis.

26週，沒錯。 26 週主要終點分析。

Okay. Good thank you.

好的。好的謝謝你。

You're welcome.

不客氣。

Thank you George.

謝謝喬治。

Joel Beatty, Baird.

喬爾·比蒂，貝爾德。

Hi, this is Ben on for the Joel. Thanks for taking the question. What gives you confidence that payers would support, or payers would recover post-transplant maintenance revumenib therapy is not in the FDA label?

大家好，我是喬爾的本。感謝您提出問題。是什麼讓您相信付款人會支持或付款人會恢復移植後維持 revumenib 療法不在 FDA 標籤中？

Yeah, thanks for the question. Well, look, I think the experienced physicians have been treating patients for AML and providing abatement treatment to those patients who again, are at high risk of relapse. That is seems to be a very important treatment decision granted by the -- is given by the or are taken by the physician.

是的，謝謝你的提問。好吧，我認為經驗豐富的醫生一直在治療 AML 患者，並為那些復發風險很高的患者提供緩解治療。這似乎是由醫生做出或做出的非常重要的治療決定。

And none of these relapse/refractory agents that have been approved have a maintenance label. So it's a sort of a tried-and-true experience with other agents that gives us confidence that this is something that the that physicians can do, and payers will abide by. I think the there is a pharmacoeconomic analysis. Of course, that supports this, these are not inexpensive therapies, but these are very seriously ill patients who aren't able to get to a steady state.

而且這些已獲批准的復發/難治性藥物都沒有維護標籤。因此，這是一種與其他代理商一起經過考驗的真實經驗，讓我們相信這是醫生可以做的事情，也是付款人會遵守的事情。我認為有藥物經濟學分析。當然，這支持了這一點，這些療法並不便宜，但這些都是病情非常嚴重的患者，無法達到穩定狀態。

And so if you can keep them in remission for a long period of time and keep them out of a hospital, that's a very positive driver for any payer. So I've also mentioned that this kind of experience can get into the guidelines, and you see it in the in the guidelines as well.

因此，如果你能讓他們長期處於緩解狀態並使他們遠離醫院，這對任何付款人來說都是一個非常積極的推動力。所以我也提到這種經驗可以進入指南，你在指南中也看到了。

And so payers tend to abide by those guidelines and in making the reimbursement the reimbursement decision. So I think there are multiple factors in support of this paradigm. And I also mentioned that these are rare diseases. And so payer, not one payer is impacted dramatically or disproportionately, I should say, by high-priced therapy being given over an extended period of time.

因此，付款人傾向於遵守這些準則並做出報銷決定。所以我認為有多種因素支持這種範式。我還提到這些都是罕見疾病。因此，我應該說，付款人，沒有一個付款人會受到長期高價治療的巨大或不成比例的影響。

So I think that's all kind of factors into the value when we hear from physicians that they do this, and they have very little intervention from payers to and to stop this from happening there seems to be supportive setup. So that's what I can tell you.

因此，我認為，當我們從醫生那裡聽到他們這樣做時，所有這些因素都會影響價值，而且付款人幾乎沒有乾預並阻止這種情況發生，似乎有支持性的設置。這就是我可以告訴你的。

That completes the Q&A section of the call. I will now hand back Michael for closing remarks.

通話的問答部分就這樣完成了。現在我將請麥可作結束語。

Thank you, operator, and thank you all. We appreciate you tuning in tonight. and we look forward to seeing you at our planned investor events, including the Cowen Fall Oncology Summit tomorrow on the Stifel Conference on November 14, as well as the ASH meeting in December that we talked a lot about today. With that, I wish you a great evening. Thank you so much.

謝謝運營商，也謝謝大家。感謝您今晚的收聽。我們期待在我們計劃的投資者活動中見到您，包括明天 11 月 14 日在 Stifel 會議上舉行的 Cowen Fall 腫瘤學峰會，以及我們今天討論了很多的 12 月 ASH 會議。在此，祝您有個美好的夜晚。太感謝了。