Kura Oncology Inc (KURA) 2025 Q3 法說會逐字稿

Good day, everybody. My name is Dani, and I will be your conference operator today. At this time, I would like to welcome you to the Kura Oncology third-quarter 2025 conference call. (Operator Instructions)

大家好。我叫丹妮，今天我將擔任你們的會議接線生。此時此刻，我謹代表 Kura Oncology 向各位歡迎，歡迎參加 2025 年第三季電話會議。（操作說明）

At this time, I would like to turn the call over to Greg Mann from Kura Oncology. Thank you.

此時，我想把電話轉給 Kura Oncology 的 Greg Mann。謝謝。

Thank you, Dani. Good morning, and welcome to Kura Oncology's third-quarter 2025 conference call. Joining the call today are Dr. Troy Wilson, President and Chief Executive Officer; Tom Doyle, Senior Vice President, Finance and Accounting; Dr. Mollie Leoni, Chief Medical Officer; and Brian Powl, Chief Commercial Officer, are also on the call and available to answer questions.

謝謝你，丹妮。早安，歡迎參加 Kura Oncology 2025 年第三季電話會議。今天參加電話會議的有：總裁兼首席執行官特洛伊·威爾遜博士；財務和會計高級副總裁湯姆·多伊爾；首席醫療官莫莉·萊奧尼博士；以及首席商務官布萊恩·鮑爾，他們也參加了電話會議，並可以回答問題。

Before I turn the call over to Dr. Wilson, we remind you that today's call will include forward-looking statements based on current expectations. Such statements represent management's judgment as of today, and may involve risks and uncertainties that cause actual results to differ materially from expected results. Please refer to Kura's filings with the SEC which are available from the SEC or on the Kura Oncology website for information concerning risk factors that could affect the company.

在將電話交給威爾遜博士之前，我們提醒各位，今天的電話會議將包含基於當前預期的前瞻性陳述。此類聲明代表管理階層截至今日的判斷，可能涉及風險和不確定性，導致實際結果與預期結果有重大差異。有關可能影響公司的風險因素的信息，請參閱 Kura 向美國證券交易委員會提交的文件，這些文件可從美國證券交易委員會或 Kura Oncology 網站上獲取。

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

這樣，我就把電話交給特洛伊了。

Thank you, Greg. Good morning, and thank you all for joining our third-quarter financial results conference call. Over the past quarter, we've continued to significantly advance both our clinical pipeline as well as preparations for the anticipated commercial launch of ziftomenib, our once-daily investigational menin inhibitor for acute myeloid leukemia.

謝謝你，格雷格。早安，感謝各位參加我們第三季財務業績電話會議。在過去的一個季度裡，我們繼續大幅推進臨床研發管線，並為即將上市的每日一次的急性髓性白血病研究藥物 ziftomenib 做好了準備。

I'll begin with an update on zifto followed by brief remarks on our commercial readiness and our Farnesyl Transferase Inhibitor Program. The FDA review of ziftomenib for treatment of patients with relapsed and refractory NPM1 mutated AML remains on track, with a PDUFA target action date of November 30, 2025. Communication with FDA continues to be open and constructive, and we remain focused on achieving a successful review outcome.

我將首先介紹 zifto 的最新情況，然後簡要談談我們的商業化準備情況和法尼基轉移酶抑制劑計劃。FDA 對 ziftomenib 用於治療復發和難治性 NPM1 突變 AML 患者的審查仍在按計劃進行，PDUFA 目標行動日期為 2025 年 11 月 30 日。我們與FDA的溝通一直保持開放和建設性，我們將繼續專注於成功的審查結果。

Based on clinical data from the KOMET-001 study, which has been presented at major medical meetings and published in the Journal of Clinical Oncology in September, we're confident ziftomenib has a differentiated and favorable benefit-risk profile, and if approved, ziftomenib could potentially reset the commercial landscape and become the menin inhibitor of choice for eligible patients.

根據 KOMET-001 研究的臨床數據（該研究已在主要醫學會議上發表，並於 9 月發表在《臨床腫瘤學雜誌》上），我們相信 ziftomenib 具有差異化和有利的獲益風險比，如果獲得批准，ziftomenib 有可能重塑商業格局，並成為符合條件的患者的首選 menin 抑製劑。

While the regulatory review process for ziftomenib progresses, our clinical team continues to execute on a strategic development plan targeted at addressing the large unmet need beyond the relapsed refractory setting where we believe ziftomenib's benefit risk profile will be even more competitive and more impactful for patients.

在 ziftomenib 的監管審查過程中，我們的臨床團隊繼續執行一項策略發展計劃，旨在解決復發難治性治療領域之外的巨大未滿足需求。我們相信，在復發難治性治療領域，ziftomenib 的獲益風險比將更具競爭力，對病患的影響也將更大。

At EHA earlier this year, we reported updated combination data for ziftomenib with 7+3 intensive chemotherapy in newly diagnosed NPM1-mutant and KMT2A-rearranged AML. These data were very encouraging, showing high rates of complete remission and MRD negativity in over 70 patients across the combination cohorts, with a safety profile consistent with what is expected in patients treated with 7+3 alone. These results highlight ziftomenib's potential as an early intervention, offering a meaningful opportunity to improve patient outcomes.

在今年稍早的 EHA 會議上，我們報告了 ziftomenib 與 7+3 強化化療聯合治療新診斷的 NPM1 突變和 KMT2A 重排 AML 的最新數據。這些數據非常令人鼓舞，在聯合治療組的 70 多名患者中，完全緩解率和 MRD 陰性率都很高，安全性與單獨接受 7+3 治療的患者預期的安全性一致。這些結果凸顯了齊夫托美尼作為早期介入手段的潛力，為改善患者預後提供了有意義的機會。

Yesterday, we announced acceptance of two oral presentations at ASH, which will feature data on ziftomenib in combination with venetoclax and azacitidine chemotherapy. Both abstracts, one in the newly diagnosed setting, and the second, in the relapsed refractory setting, reported high response rates and MRD negativity with a safety profile consistent with previous reports.

昨天，我們宣佈在 ASH 會議上接受了兩份口頭報告，報告將重點介紹 ziftomenib 與 venetoclax 和 azacitidine 化療聯合應用的數據。兩篇摘要，一篇針對新診斷的患者，另一篇針對復發難治性患者，均報告了較高的緩解率和 MRD 陰性，且安全性與先前的報告一致。

The abstracts used data cut off of June 25, 2025, and updated results reflecting additional follow-up will be reported in the oral presentations next month. We plan to host a virtual investor and analyst event to discuss these ASH presentations on Monday, December 8, at 12:30 PM Eastern Time. Details will be available on our website.

摘要中使用的數據截止於 2025 年 6 月 25 日，反映後續研究結果的更新報告將在下個月的口頭報告中公佈。我們計劃於美國東部時間 12 月 8 日星期一下午 12:30 舉辦一場虛擬投資者和分析師活動，討論這些 ASH 簡報。詳情請見我們的網站。

Encouraged by these positive results, we've advanced rapidly into our KOMET-017 frontline Phase III trials. KOMET-017 comprises two randomized, double-blind, placebo-controlled trials to evaluate ziftomenib in combination with both intensive 7+3, and non-intensive VEN/AZA chemotherapy regimens in patients with newly diagnosed NPM1-mutant or KMT2A-rearranged AML.

受這些正面結果的鼓舞，我們迅速推進了 KOMET-017 一線 III 期試驗。KOMET-017 包括兩項隨機、雙盲、安慰劑對照試驗，旨在評估 ziftomenib 與強化 7+3 化療方案和非強化 VEN/AZA 化療方案聯合用於治療新診斷的 NPM1 突變或 KMT2A 重排 AML 患者。

The program aims to advance ziftomenib to the frontline setting with potential to treat patients earlier in their disease course when the opportunity to alter its trajectory is greatest. We're targeting enrollment at over 150 global sites with a large proportion in the US. Each KOMET-017 trial includes dual primary endpoints to support potential US accelerated and full approvals. The intensive chemotherapy combination study evaluates MRD-negative complete response, or CR, and event-free survival. The non-intensive chemotherapy combination study assesses CR and overall survival.

該計劃旨在將 ziftomenib 推進到一線治療階段，以便在疾病早期階段治療患者，從而最大程度地改變疾病的進程。我們的目標是在全球 150 多個地點招募學員，其中很大一部分將在美國。每項 KOMET-017 試驗都包含雙重主要終點，以支持潛在的美國加速批准和完全批准。這項強化化療聯合研究評估了 MRD 陰性完全緩解 (CR) 和無事件存活期。非強化化療聯合研究評估了完全緩解率和總存活期。

Site activation is accelerating in each of these company-sponsored registrational trials, and patient enrollment is progressing well. Continuing this momentum, last month we opened a trial cohort to assess ziftomenib combined with 7+3 induction chemotherapy and quizartinib, an approved FLT3 inhibitor in patients with newly diagnosed AML, harboring FLT3 ITD and PM1-mutant co-mutations. FLT3 mutations represent one of the most common and challenging genetic mutations in AML with limited durable treatment options.

在這些公司贊助的註冊試驗中，試驗點的啟動速度正在加快，病患招募工作也進展順利。延續這一勢頭，上個月我們啟動了一個試驗隊列，以評估 ziftomenib 與 7+3 誘導化療和 quizartinib（一種已獲批准的 FLT3 抑製劑）聯合用於新診斷的 AML 患者（攜帶 FLT3 ITD 和 PM1 突變共突變）的療效。FLT3 突變是 AML 中最常見且最具挑戰性的基因突變之一，目前持久有效的治療選擇有限。

Our preclinical studies suggest ziftomenib and quizartinib synergized to enhance activity without undue toxicity. Note, this effort also builds on our clinical experience with the combination of ziftomenib and gilteritinib in the relapsed refractory NPM1-mutant setting. Enrollment in that trial has been robust, and we intend to present preliminary Phase 1 data at a major medical meeting next year. With these studies now underway, ziftomenib development is active in all three major frontline settings, collectively representing up to 50% of incident AML cases in the US.

我們的臨床前研究表明，ziftomenib 和 quizartinib 具有協同作用，可在不產生過度毒性的情況下增強活性。請注意，這項工作也建立在我們利用 ziftomenib 和 gilteritinib 聯合治療復發難治性 NPM1 突變患者的臨床經驗之上。該試驗的入組情況良好，我們計劃明年在一次重要的醫學會議上公佈初步的 1 期數據。隨著這些研究的開展，ziftomenib 的開發在所有三個主要一線治療領域都處於活躍狀態，這些領域加起來占美國新發 AML 病例的 50%。

Turning now to commercial preparations, our teams are launch ready and confident in our execution plan across the commercial organization from marketing, market access as well as patient support and sales analytics, field operations, and sales. Our teams are fully mobilized and prepared to execute as soon as ziftomenib is approved.

現在轉向商業準備，我們的團隊已做好上市準備，並對我們在整個商業組織中的執行計劃充滿信心，包括行銷、市場准入以及患者支援和銷售分析、現場運營和銷售。一旦 ziftomenib 獲得批准，我們的團隊已全面動員並準備立即執行。

Our disease-awareness campaigns have exceeded their targets. Our pre-approval information exchanges with key payers and other market decision-makers are complete, offering us confidence that we will facilitate rapid access and uptake. Our limited distribution network is fully aligned and ready to support product upon approval. And our team of experienced oncology account managers is already engaged in profiling target accounts.

我們的疾病防治宣傳活動已經超額完成了目標。我們與主要付款方和其他市場決策者的預審批資訊交流已經完成，這讓我們有信心促進快速獲取和推廣。我們有限的分銷網絡已完全就緒，一旦產品獲得批准，即可提供分銷支援。我們經驗豐富的腫瘤客戶經理團隊已經開始對目標客戶進行畫像分析。

In early October, we and our partner, Kyowa Kirin, held a joint launch readiness meeting where our two-field teams of Kura and Kyowa Kirin, what we fondly call 1K, completed their training and pre-certification. The excitement and alignment across both organizations is palpable, and the 1K team stands ready to deliver upon approval.

10 月初，我們和合作夥伴 Kyowa Kirin 舉行了一次聯合啟動準備會議，我們 Kura 和 Kyowa Kirin 的兩個現場團隊（我們親切地稱之為 1K）完成了培訓和預認證。兩個組織內部的興奮和共識顯而易見，1K 團隊已做好準備，一旦獲得批准，將立即交付成果。

Turning now to our farnesyl-transferase inhibitor portfolio, last month, we presented new clinical data highlighting the potential of FTIs to safely combine with major classes of targeted therapies, including PI3 kinase alpha inhibitors, KRAS inhibitors, and anti-angiogenic tyrosine kinase inhibitors to overcome resistance pathways and enhance anti-tumor activity.

現在來說說我們的法尼基轉移酶抑制劑產品組合。上個月，我們公佈了新的臨床數據，重點介紹了 FTI 與主要標靶療法類別（包括 PI3 激酶 α 抑制劑、KRAS 抑制劑和抗血管生成酪氨酸激酶抑製劑）安全聯合使用的潛力，以克服抗藥性途徑並增強抗腫瘤活性。

In our FIT-001 Phase 1 trial evaluating darlafarnib, our next-generation FTI, in combination with cabozantinib in patients with Renal Cell Carcinoma, we observed a manageable safety profile across multiple dose levels of each agent, including at the full-labeled dose of cabozantinib. Anti-tumor activity was seen across all dose combinations, including in-patients with prior exposure to cabozantinib. The objective response rate, or ORR, was 33% to 50% in clear cell renal cell carcinoma, and 17% to 50% in patients with prior cabozantinib exposure.

在我們評估下一代 FTI darlafarnib 與 cabozantinib 聯合治療腎細胞癌患者的 FIT-001 1 期試驗中，我們觀察到每種藥物在多個劑量水平下均具有可控的安全性，包括 cabozantinib 的全劑量。所有劑量組合均顯示出抗腫瘤活性，包括先前接受過卡博替尼治療的患者。透明細胞腎細胞癌的客觀緩解率（ORR）為 33% 至 50%，而先前接受過卡博替尼治療的患者的 ORR 為 17% 至 50%。

The current HN trial evaluates tipifarnib, our first-generation FTI, with alpelisib in patients with PIK3CA-dependent head and neck squamous cell carcinoma. This combination also demonstrated a manageable safety profile and robust anti-tumor activity in a heavily pre-treated patient population, where meaningful benefit would not be expected from either agent alone. An ORR of 47% was observed at a dose of tipifarnib of 1,200 milligrams per day, and alpelisib at 250 milligrams per day.

目前的 HN 試驗評估了我們的第一代 FTI 替比法尼與阿培利西佈在 PIK3CA 依賴性頭頸部鱗狀細胞癌患者中的療效。這種組合療法在大量接受過預先治療的患者群體中也展現出可控的安全性和強大的抗腫瘤活性，而單獨使用任何一種藥物都無法帶來顯著的益處。tipifarnib 劑量為每天 1200 毫克時，ORR 為 47%；alpelisib 劑量為每天 250 毫克時，ORR 為 47%。

We see tremendous promise in darlafarnib and the broader potential of farnesyl-transferase inhibition as a differentiated mechanism to extend the reach of precision oncology. With the potential to enhance activity of PI3 kinase alpha inhibitors, KRAS inhibitors, and TKIs, darlafarnib represents a very substantial commercial opportunity with the potential to address more than 200,000 incident patients annually in the US alone.

我們看到了達拉法尼的巨大前景，以及法尼基轉移酶抑製作為一種差異化機制在擴大精準腫瘤學應用範圍方面的更廣泛潛力。達拉法尼具有增強 PI3 激酶 α 抑制劑、KRAS 抑制劑和 TKI 活性的潛力，代表著非常巨大的商業機會，僅在美國每年就有可能治療超過 20 萬名新發患者。

We view our FTI platform as a strategically important pillar of growth that complements our leadership in men and inhibition. Our dual-pipeline strategy positions Kura with two clinically validated mechanisms that address some of the most pressing needs in precision oncology. We expect to have more to share regarding our FTI clinical development plans and business-development strategy in 2026, supported by a steady cadence of data presentations at medical meetings throughout the year.

我們認為 FTI 平台是成長的重要策略支柱，它補充了我們在男性和抑制領域的領先地位。我們的雙管齊下策略使 Kura 擁有兩種經過臨床驗證的機制，可解決精準腫瘤學領域中一些最迫切的需求。我們預計將在 2026 年分享更多關於 FTI 臨床開發計劃和業務發展策略的信息，並全年透過醫學會議持續發布數據。

Kura remains in a strong financial position to execute across our pipeline, advance the development of ziftomenib, and support our commercialization activities. Our partnership with Kyowa Kirin has enabled us to invest in a robust, expansive, and accelerated development plan for ziftomenib. We recently received two $30 million milestone payments payable for the first patients dosed in the two KOMET-017 Phase 3 trials, which brings the total milestones received this year to $105 million. We expect approximately $315 million more in near-term milestone payments, including a substantial milestone payment associated with commercial launch of ziftomenib.

Kura 仍擁有強勁的財務實力，能夠執行我們所有的研發管線，推進 ziftomenib 的開發，並支援我們的商業化活動。我們與協和麒麟株式會社的合作使我們能夠投資於ziftomenib的強大、廣泛和加速的開發計劃。我們最近收到了兩筆 3000 萬美元的里程碑付款，用於支付在兩項 KOMET-017 3 期試驗中接受治療的首批患者，這使得我們今年收到的里程碑付款總額達到 1.05 億美元。我們預計近期還將收到約 3.15 億美元的里程碑付款，其中包括與 ziftomenib 商業上市相關的巨額里程碑付款。

This is consistent with the $420 million in near-term milestones we announced at the inception of the partnership with Kyowa Kirin last November. We reported pro forma cash of $609.7 million for the period. This figure includes milestone payments received in October and November 2025, and reflects a strong capital position to advance our pipeline through key clinical and regulatory milestones.

這與我們去年 11 月與協和麒麟建立合作關係之初宣布的 4.2 億美元的近期里程碑目標一致。該期間的備考現金餘額為 6.097 億美元。這個數字包括 2025 年 10 月和 11 月收到的里程碑付款，反映了我們強大的資本實力，能夠推動我們的產品線通過關鍵的臨床和監管里程碑。

I'll now turn it over to Tom, who will review the third-quarter financial results.

現在我將把發言權交給湯姆，他將審閱第三季的財務表現。

Thank you, Troy. Collaboration revenue from our Kyowa Kirin partnership for the third quarter of 2025 was $20.8 million compared to no revenue for the third quarter of 2024. Research and development expenses for the third quarter of 2025 were $67.9 million compared to $41.7 million for the third quarter of 2024. General and administrative expenses for the third quarter of 2025 were $32.8 million compared to $18.2 million for the same period of 2024. Net loss for the third quarter of 2025 was $74.1 million compared to a net loss of $54.4 million for the third quarter of 2024. This included non-cash, share-based compensation expense of $11 million compared to $8.3 million for the same period in 2024.

謝謝你，特洛伊。2025 年第三季度，我們與協和麒麟的合作收入為 2,080 萬美元，而 2024 年第三季則沒有收入。2025 年第三季的研發費用為 6,790 萬美元，而 2024 年第三季的研發費用為 4,170 萬美元。2025 年第三季的一般及行政費用為 3,280 萬美元，而 2024 年同期為 1,820 萬美元。2025 年第三季淨虧損為 7,410 萬美元，而 2024 年第三季淨虧損為 5,440 萬美元。其中包括非現金的股份支付費用 1,100 萬美元，而 2024 年同期為 830 萬美元。

As of September 30, 2025, Kura had cash, cash equivalents, and short-term investments of $549.7 million compared to $727.4 million as of December 31, 2024. As adjusted for the $60 million in KOMET-017 milestone payments under our collaboration agreement with Kyowa Kirin and Kura had on a pro forma basis $609.7 million in cash, cash equivalents, and short-term investments as of September 30, 2025.

截至 2025 年 9 月 30 日，Kura 的現金、現金等價物和短期投資為 5.497 億美元，而截至 2024 年 12 月 31 日，這一數字為 7.274 億美元。扣除根據我們與協和麒麟株式會社的合作協議支付的 6000 萬美元 KOMET-017 里程碑付款後，截至 2025 年 9 月 30 日，Kura 公司按備考基準持有現金、現金等價物和短期投資 6.097 億美元。

Based on our current operating plans, we believe that our cash, cash equivalents, and short-term investments as of the end of the third quarter will be sufficient to fund our current operating expenses in 2027. And if we include anticipated collaboration funding under the Kyowa Kirin agreement, Kura's financial resources should support advancement of our ziftomenib AML program through top-line results in our front-line combination program.

根據我們目前的營運計劃，我們相信截至第三季末，我們的現金、現金等價物和短期投資足以支付我們 2027 年的當前營運費用。如果算上根據協和麒麟協議預期獲得的合作資金，Kura 的財政資源應該能夠透過我們一線聯合治療方案的初步結果，支持我們 ziftomenib AML 計畫的推進。

With that, I'll turn the call back over to Troy.

這樣，我就把電話轉回給特洛伊了。

Thank you, Tom. Before we open the call for questions, let me just briefly highlight the key milestones we expect over the coming months and into next year. For ziftomenib and our menin inhibitor programs, we look forward to continued engagement with FDA reviewers as we approach our PDUFA target action date of November 30 for ziftomenib as a monotherapy for patients with relapsed refractory NPM1-mutant AML.

謝謝你，湯姆。在正式開始提問之前，請容許我簡要介紹我們預計在未來幾個月以及明年實現的關鍵里程碑。對於 ziftomenib 和我們的 menin 抑制劑項目，我們期待與 FDA 審查員繼續互動，因為我們即將迎來 11 月 30 日的 PDUFA 目標行動日期，屆時 ziftomenib 將作為複發難治性 NPM1 突變 AML 患者的單藥療法。

Present preliminary clinical data in newly-diagnosed NPM1 mutant AML and updated clinical data in relapsed refractory NPM1-mutant and KMT2A rearranged AML from our KOMET-007 cohorts evaluating ziftomenib in combination with VEN/AZA at the ASH Annual Meeting to be held next month in Orlando. And finally, presenting preliminary clinical data from the KOMET-008 cohort evaluating ziftomenib in combination with the FLT3 inhibitor gilteritinib in patients with relapsed refractory NPM1 mutant AML in 2026.

在下個月於奧蘭多舉行的 ASH 年會上，我們將展示 KOMET-007 隊列中新診斷的 NPM1 突變 AML 的初步臨床數據，以及復發難治性 NPM1 突變和 KMT2A 重排 AML 的最新臨床數據，這些隊列評估了 ziftomenib 與 VEN/AZA 聯合用藥的療效。最後，我們將介紹 KOMET-008 隊列的初步臨床數據，該隊列評估了 2026 年 ziftomenib 與 FLT3 抑制劑 gilteritinib 聯合治療復發難治性 NPM1 突變 AML 患者的療效。

For our Farnesyl Transferase Inhibitor Programs, we expect to initiate one or more expansion cohorts of darlafarnib and cabozantinib in patients with advanced renal cell carcinoma in the first half of 2026, to present updated dose escalation data from the combination of darlafarnib and cabozantinib in advanced renal cell carcinoma in 2026, to present clinical data from the combination of darlafarnib and adagrasib in patients with KRAS G12C mutated solid tumor indications in 2026.

對於我們的法尼基轉移酶抑制劑項目，我們預計將於 2026 年上半年啟動一項或多項針對晚期腎細胞癌患者的達拉法尼和卡博替尼的擴展隊列研究，並於 2026 年公佈達拉法尼和卡博替尼聯合治療晚期腎細胞癌的最新劑量遞增數據，以及達拉法尼和阿達格拉西布細胞聯合治療晚期腎細胞癌的最新劑量遞增數據，以及達拉法尼和阿達格拉西布複合物的臨床數據。

With that, Danny, we're ready to begin the question-and-answer session.

丹尼，那麼，我們現在可以開始問答環節了。

(Operator Instructions) Jonathan Chang, Leerink Partners.

（操作說明）Jonathan Chang，Leerink Partners。

This is Albert Agustinus on for Jonathan Chang. Thank you for taking my questions. What do you foresee will be the makeup of account types that you are trying to penetrate for zifto launch? Are there any particular account types that you are focusing on? And also, are there any plans to include zifto in the NCCN guidelines? Thank you.

這裡是阿爾伯特·奧古斯蒂努斯，替喬納森·張報。謝謝您回答我的問題。您預計在 Zifto 上線初期，您希望滲透的帳戶類型會是什麼？您目前重點關注哪些類型的帳戶？另外，是否有計劃將Zifto納入NCCN指南？謝謝。

Sure. Thanks, Albert. In general, we're going to try to limit it to one question. The second one is easy, but please, if folks can limit it to one question so we can get everybody. Brian, let me ask you if you can take Albert's two questions in turn.

當然。謝謝你，阿爾伯特。一般來說，我們會盡量只提一個問題。第二個問題很簡單，但請大家盡量只提一個問題，這樣我們才能照顧到所有人。布萊恩，請問你能依序回答阿爾伯特的兩個問題嗎？

Sure, absolutely. Thanks, Albert, for the questions. So our expected account types here are typically going to be the specialty hematologists. We anticipate a mix of large academic institutions as well as some of the larger community oncology practices. It's going to be similar. Well, I think we'll get into our overall targeting strategy, but probably about 4,000 HCPs that we're targeting.

當然可以。謝謝阿爾伯特提出的問題。因此，我們預期的客戶類型通常是血液科專家。我們預計參會機構既包括大型學術機構，也包括一些規模較大的社區腫瘤診所。情況差不多。嗯，我想我們會深入探討我們的整體目標策略，但我們可能瞄準了大約 4,000 名醫療保健專業人員。

Within that range, I'd say probably 78% of that is going to be the academic setting, and then the rest of the focus will be on the community oncology practices that are treating those AML patients and particularly the relapsed refractory patients.

在這個範圍內，我認為大約 78% 將是學術環境，其餘的重點將放在治療 AML 患者，特別是復發難治性患者的社區腫瘤診所。

To your second question, just quickly to answer, yeah, our plans are to submit the KOMET-001 data on the basis of our approval. Soon after approval, you can't submit to the NCCN for a listing until you have FDA approval. So our plans are to submit that within days of approval.

關於你的第二個問題，我簡單回答一下，是的，我們的計劃是根據我們的批准提交 KOMET-001 數據。獲得批准後不久，在獲得 FDA 批准之前，您無法向 NCCN 提交收錄申請。因此，我們的計劃是在獲得批准後的幾天內提交該申請。

Lee Watsek, Cantor Fitzgerald.

李‧沃塞克，康托‧費茲傑拉。

Congrats on the progress. Maybe just one on the ASH update. Can you just talk about what we should expect for the actual oral presentations versus what's in the abstract released yesterday?

恭喜你取得進展。或許只是關於ASH更新的一個問題。您能否談談實際口頭報告的內容與昨天發布的摘要有何不同？

Yeah. Thanks, Lee, for the question. Mollie, do you want to take that one?

是的。謝謝李的提問。莫莉，你想選那個嗎？

Sure. As Troy pointed out, the data cut was back in June for what was submitted to ASH. So obviously, we've got many months more worth of data. So you'll see not only more valuable patients being able to be reported and the evolution of responses across the whole patient population, you'll also see new information about MRD negativity as well as just longer follow-up and safety information in general.

當然。正如 Troy 指出的那樣，提交給 ASH 的數據早在 6 月就被截斷了。顯然，我們還有好幾個月的數據。因此，您不僅會看到更多有價值的患者能夠被報告，以及整個患者群體的反應演變，還會看到有關 MRD 陰性的新信息，以及更長的隨訪和一般安全性信息。

Salim Syed, Mizuho Securities.

Salim Syed，瑞穗證券。

Love the revised format of the call. Appreciate it. I guess one for us, Troy, maybe just on the new label that we got from Syndax, which includes Torsades now in the black box. Just curious, there seems to be varying views on if this actually matters or not. What does it mean for you? What does it mean for the space as you think about your own NPM1 launch and also as you progress here towards first line in particular, which I guess there's a view out there that it doesn't matter because first line maybe is that you wouldn't see the Torsades as much. But curious to get your view as the space evolves here. Thank you.

很喜歡這次通話形式的修改。謝謝。我想我們自己會有一首，Troy，也許就收錄在我們從 Syndax 那裡拿到的新唱片裡，現在 Torsades 也收錄在黑盒唱片裡了。只是好奇，大家似乎對此看法不一，不知道這是否真的重要。這對你來說意味著什麼？當你考慮自己的 NPM1 發射，以及當你向第一線推進時，這對太空意味著什麼？我猜有一種觀點認為這並不重要，因為第一線可能意味著你不會經常看到 Torsades 現象。我很想聽聽您對這個空間未來發展的看法。謝謝。

Yes. Salim, thanks for the question. I'm glad you're appreciating the new format. There's a lot that I think we can talk about here. We'll have more to say if and when we get approval of ziftomenib here coming up very quickly on our PDUFA action date. A few thoughts, and I'm going to give my comments, and then I'm going to ask Mollie for hers, because she really needs to speak to this from a clinical perspective.

是的。薩利姆，謝謝你的提問。很高興你喜歡這種新形式。我覺得我們這裡有很多可以討論的話題。如果 ziftomenib 獲得批准，我們將在 PDUFA 批准日到來發表更多評論。我有一些想法，我會發表一些評論，然後我會請莫莉發表她的看法，因為她真的需要從臨床角度談談這個問題。

But first of all, Salim, maybe the magnitude of the risk. This is a box warning. So a box warning is as serious as one can have as far as warnings and precautions. It isn't so much the frequency, it is the severity, particularly Torsades, right?

但首先，薩利姆，或許應該考慮風險的程度。這是警告訊息。因此，就警告和預防措施而言，方框警告是最嚴肅的警告之一。重要的不是發作頻率，而是嚴重程度，特別是尖端扭轉型室性心搏過速，對吧？

Torsades, for everyone on the call, I mean, we're talking about a risk of sudden cardiac death. There are numbers that are getting bandied around that it's one in a thousand, it's not. You don't typically see this as much in younger patients, so you really need to focus on the NPM1 population, and we're looking at maybe somewhere between one in a hundred, or perhaps even more frequent than that.

對於所有參與通話的人來說，我指的是尖端扭轉型室性心搏過速，也就是猝死的風險。坊間流傳著一種說法，說這種可能性是千分之一，但事實並非如此。在年輕患者中，這種情況並不常見，因此我們需要專注於 NPM1 族群，我們估計其發生率可能在百分之一左右，甚至可能更高。

And I guess I would just put it to anyone, right? If you have two agents, both of which are efficacious, but one of which has a one in a hundred or more chance of sudden cardiac death, what are you going to choose? I think that's where we feel increasingly confident based on the clinical data that's been presented at major medical meetings, it's published in JCO. We're going to have a differentiated and favorable benefit-risk profile. And I think that'll start in the relapsed refractory setting.

我想我也會問任何人這個問題，對吧？如果有兩種藥物，都有效，但其中一種有百​​分之一或更高的猝死幾率，你會選擇哪一種？我認為，根據在主要醫學會議上公佈的臨床數據（已發表在 JCO 上），我們對此越來越有信心。我們將擁有差異化且有利的收益風險比。我認為這將從復發難治性疾病的治療開始。

But to the comment about it's less relevant in the frontline, the risk doesn't go away. In fact, what you're dealing with is those patients are healthier, and they're presumably going to stay on therapy for much longer. So if anything, you want a more favorable benefit-risk profile in that population, which means that if – you’re -- the ability to differentiate on a favorable safety profile that doesn't have a box warning for QTC prolongation and Torsades becomes even more significant.

但對於「在前線風險較小」這種說法，風險並不會消失。事實上，這些患者身體狀況較好，而且他們很可能需要接受更長時間的治療。所以，如果有什麼不同的話，你希望該族群的獲益風險比更有利，這意味著，如果你——區分具有良好安全性特徵且沒有 QT 間期延長和尖端扭轉型室性心動過速警告的藥物的能力就變得更加重要了。

Let's see. The last thing I'll say before I turn it over to Mollie is the ASH abstract, there was a giant data dump. Despite comments from some others that there's really no room for another menin inhibitor, there's a lot of activity in the menin space from us and from other competitors. You can parse through the abstracts.

讓我們來看看。在把發言權交給 Mollie 之前，我最後要說的是 ASH 摘要，這次會議的資料量非常龐大。儘管有些人評論說，真的沒有空間再引入另一種menin抑制劑了，但我們和其他競爭對手在menin領域仍然非常活躍。你可以仔細閱讀摘要。

What I think you'll see is that the benefit-risk profiles of the different agents are continuing to be defined as we go, and I would draw your attention not only to the activity, and all of these agents are very active, and that's good for patients, but the safety and tolerability is also coming much more into focus, and I would invite you to look at the various combinations.

我認為你們會看到，隨著研究的進行，不同藥物的獲益風險比正在不斷明確。我不僅要讓你們專注於藥物的活性（所有這些藥物的活性都很高，這對患者來說是好事），還要讓你們專注於藥物的安全性和耐受性。我建議你們研究一下各種藥物組合。

But Mollie, let me invite you to add any thoughts or comments maybe to build on mine.

不過莫莉，我想邀請你補充一些想法或評論，或許可以補充我的觀點。

Absolutely. As Troy said, it's not the black box warning that in and of itself is something to focus on. It's what it means the data has shown. And one of the best ways of understanding that is to look at the FDA's actual guidance document on the topic. It is very clear that once a drug causes at least a 20-millisecond change in the QTC prolongation, it is now considered to be significantly more likely to cause sudden cardiac death. It's not just Torsades we're looking at; it's any ventricular arrhythmia. And so the risk just becomes so much more increased. That is why they put the black box.

絕對地。正如特洛伊所說，黑框警告本身並不是值得關注的重點。這就是數據所顯示的結果。了解這一點的最佳方法之一就是查看 FDA 關於該主題的實際指導文件。很明顯，一旦某種藥物導致 QTC 間期延長至少 20 毫秒，那麼它現在被認為更有可能導致猝死。我們關注的不僅是尖端扭轉型室性心動過速；而是任何室性心律不整。因此，風險就大大增加了。這就是他們放置黑盒子的原因。

So it's understanding what data requires a black box warning that becomes really important in this situation and to patients who are trying to decide between options of what risks they are willing to take on and what risks they would rather avoid if they have the option to do so.

因此，了解哪些數據需要黑框警告就變得非常重要，這對於那些試圖在各種選擇中做出決定的患者來說至關重要，他們需要考慮自己願意承擔哪些風險，以及如果可以選擇的話，他們更願意避免哪些風險。

And as Troy pointed out, while something like differentiation syndrome is very well mitigated in earlier lines with combination therapy, you would actually potentially expect more issues with the ability to handle -- or at least equal issues with the ability to handle QTC prolongation just because of the various medications that are going to be given as concurrent therapies and as additional oncology therapies for these patients' treatment.

正如 Troy 指出的那樣，雖然像分化綜合徵這樣的問題在早期聯合治療中得到了很好的緩解，但實際上，由於將要同時使用多種藥物作為這些患者的輔助腫瘤治療，你可能會預期在處理 QTc 延長方面出現更多問題，或者至少在處理 QTc 延長方面會出現同等程度的問題。

And it becomes more complex when deciding how to administer a drug with QTC, black box warning with other drugs that have QTC prolongation. And so dosing and monitoring become extraordinarily important versus if you're going to administer it as a monotherapy in the relapsed refractory setting.

當決定如何使用具有 QTC 延長作用的藥物，以及與其他具有 QTC 延長作用的藥物一起服用時，情況就變得更加複雜了。因此，與在復發難治性情況下作為單一療法進行給藥相比，劑量和監測變得極為重要。

And again, as Troy said, the right denominator for looking at this is really your elderly patients, where in some of our competitors we see almost a 50% rate of QTC prolongation. That is going to be your NPM1 mutant patient population. So your NPM1 mutant patient population becomes a denominator that really is more appropriate for looking at these more severe QTC prolongations and episodes of Torsades and sudden cardiac death.

正如 Troy 所說，要真正了解這個問題，正確的分母應該是老年患者，而我們的一些競爭對手中，QTC 延長的發生率接近 50%。這將會是你的 NPM1 突變患者群。因此，NPM1 突變患者群體就成了更適合用來研究這些更嚴重的 QTC 延長、尖端扭轉型室性心動過速和猝死的分母。

Charles Yu, LifeSize Capital.

Charles Yu，LifeSize Capital。

So I guess with all of that in mind, for one, what kind of level of penetration or market share would you either expect or hope to achieve relative to your first mover competitor in the space, at least in the near term, the relapse refractory setting? And can you also perhaps give a little bit more color around the ongoing points of FDA regulatory engagement that seem to be continuing on as you head close to your PDUFA date? Thank you.

所以，考慮到所有這些因素，首先，相對於該領域的先驅競爭對手，您期望或希望在短期內（至少在復發難治性領域）達到怎樣的滲透率或市場份額？此外，您能否再詳細介紹一下隨著 PDUFA 日期的臨近，FDA 監管似乎仍在進行的溝通要點？謝謝。

So Charles, I don't want to scold you. You asked two questions, and so we'll answer the first one, and then if there's time after others, we'll come back and get the second one.

查爾斯，我不想責備你。你問了兩個問題，所以我們先回答第一個問題，如果回答完其他問題後還有時間，我們會再回來回答第二個問題。

So Brian, could you please speak to Charles' first question relating to penetration and how we're going to compete with our competitor who is out there with a first-mover advantage?

那麼布萊恩，你能否回答查爾斯提出的第一個問題，即市場滲透率，以及我們將如何與擁有先發優勢的競爭對手競爭？

Yeah. Thanks, Charles, for that question. So we haven't guided on our market share penetration expectations quite yet, but what I can do is just share some of the feedback and expectations we have. So we've conducted extensive engagements with treating physicians, KOLs, community practitioners, academics, and tested our profile relative to others. And I think that the benefit-risk balance between a strong efficacy profile with good safety and tolerability that allows patients to be able to be well managed along with the combinability and even the convenience of a once-daily oral medication all come out the factors that suggest that ziftomenib has a best-in-class profile and that we'll be confident we'll be able to communicate on that best-in-class profile coming into the market.

是的。謝謝查爾斯提出的這個問題。因此，我們尚未就市場份額滲透預期給出具體說明，但我可以分享一些我們收到的回饋和預期。因此，我們與治療醫生、關鍵意見領袖、社區從業人員、學者進行了廣泛的交流，並測試了我們相對於其他機構的資格。我認為，ziftomenib 具有良好的療效、安全性和耐受性，能夠很好地管理患者，並且具有聯合用藥的便利性，每日一次口服藥物，所有這些因素都表明 ziftomenib 具有同類最佳的特性，我們有信心在產品上市後能夠宣傳其同類最佳的特性。

So without really guiding on any share calls quite yet, we anticipate -- well, we give credit that our -- we have a competitor who's already in the market, but we recognize that we anticipate both the skill of our team that we've hired that are ready to go and are ready to launch this product and the profile of the product are really going to help us to capture a majority share in this space.

因此，雖然目前還不能就任何股票份額做出具體指示，但我們預計——當然，我們承認——我們有一個已經進入市場的競爭對手，但我們認識到，我們聘請的團隊的技能，他們已經準備好推出這款產品，以及產品的特性，都將真正幫助我們在這個領域佔據多數市場份額。

(Operator Instructions) Roger Song, Jefferies.

（操作說明）羅傑‧宋，傑富瑞。

Hey, team. This is Nabil on for Roger. Thanks for taking my question. Just a quick one on the ASH data. The early data looked pretty encouraging with the CR rates and MRD negativity. As we head into the meeting, what other analyses or long-term outcomes are we expecting to see, like durability? Will we have also subgroup insights? Thank you.

嘿，團隊成員們。這裡是納比爾替羅傑報道。謝謝您回答我的問題。關於 ASH 數據，簡單說幾句。早期數據顯示，完全緩解率和微小殘留病灶陰性率都相當令人鼓舞。在會議召開之際，我們預計還會看到哪些其他分析或長期結果，例如持久性？我們是否也會有分組分析結果？謝謝。

Yeah, thanks, Nabil, for the question. Mollie, do you want to take Nabil's question?

好的，謝謝你的提問，納比爾。莫莉，你想回答納比爾的問題嗎？

Sure. As I said, the biggest thing you'll see is much longer follow-up. You'll see more granularity around the MRD negativity, breaking it down so that you have maybe some comparisons that you can make to previous VEN/AZA data to understand if there is additional impact with a targeted agent added on. And you'll see more durability, et cetera.

當然。正如我所說，你會看到的最大變化是更長的後續追蹤時間。你會看到 MRD 陰性結果的更細粒度分析，將其分解，以便你可以與先前的 VEN/AZA 數據進行比較，以了解添加標靶藥物是否會產生額外的影響。而且你會發現它更耐用等等。

And yes, we will be breaking it down by subgroups. You'll understand what our FLT3 patients look like that were in the trial, what our IDH patients look like that were in the trial. So it should just be a much more even comprehensive view of the data that we have seen thus far in our rather large patient pool that we're being able to present in both the relapse refractory and the frontline setting where you're going to see 30 to 70 patients, which is extremely robust and able to really show you more maybe the truth of what these patient populations look like. So we're excited to share it with you.

是的，我們會按小組進行細分。您將了解參與試驗的 FLT3 患者長什麼樣，參與試驗的 IDH 患者長什麼樣子。因此，這應該能讓我們更全面地了解迄今為止在我們相當大的患者群體中看到的數據，我們能夠在復發難治性治療和一線治療環境中展示這些數據，您將看到 30 到 70 名患者，這非常可靠，並且能夠真正向您展示這些患者群體的真實面貌。所以我們很高興與您分享。

Jason Zemansky, Bank of America.

傑森‧澤曼斯基，美國銀行。

Congrats on the great progress, and thank you for taking our question. Troy, I wanted to ask a follow-up regarding the commercial launch and NPM1. But is having a differentiated label enough to overcome the second-mover advantage when you think about sort of prescriber inertia? Is it more so that -- just I guess getting drug to patients? I mean, how do you overcome some of the hurdles here just given the timelines? Thanks.

恭喜你們取得如此巨大的進展，感謝你們回答我們的問題。Troy，我想就商業發布和 NPM1 詢問一些後續問題。但是，考慮到醫生的慣性，擁有差異化的標籤是否足以克服後發優勢呢？是不是只是為了把藥送到病人手中？我的意思是，考慮到時間限制，你如何克服這裡的一些障礙？謝謝。

Sure. Maybe I'll just make a quick comment, and then I'll let Brian take it, because he's really the one who should speak to this. These physicians, I mean, you all talk to them, right? They are very sophisticated, constantly taking in new data, and looking for options that offer the best benefit-risk for their patients. The patients are also extremely sophisticated.

當然。我可能只會簡單說幾句，然後就讓布萊恩來回答吧，因為他才是真正應該談論這個問題的人。我的意思是，你們都跟這些醫生談過，對吧？他們非常成熟，不斷吸收新數據，並尋找能為患者帶來最佳效益風險比的方案。這些患者也都非常精明。

They have all sorts of access to information, and they are, again, others might say it's efficacy, efficacy, efficacy. Yeah, that's important. All of these agents are efficacious, right? That's the great thing for patients. And we should all celebrate the fact that patients have multiple options. But these docs are now having conversations with their patients about the risk benefit. And there's a striking difference between the relapsed refractory setting, where a number of these patients are in-patient, versus the frontline setting, where our hope is that we send them home and they're able to stay on continuation therapy for months or even years.

他們有各種各樣的資訊獲取管道，而且，其他人可能會說，關鍵在於效率、效率、效率。是的，這很重要。這些藥物都有效，對嗎？這對患者來說是件好事。我們都應該慶幸患者現在有多種治療選擇。但現在這些醫生正在與患者討論風險效益問題。復發難治性病例與第一線治療病例之間存在顯著差異，在一線治療病例中，許多患者需要住院治療，而我們希望能夠讓他們回家，並讓他們接受數月甚至數年的後續治療。

So Jason, I mean, I'm not going to deny there is an advantage to an incumbent, but I think when you're coming forward as we believe we are with a superior benefit-risk profile in a very competitive space, I think we will see the market reached its equilibrium.

所以傑森，我的意思是，我不會否認現有企業有優勢，但我認為，當我們在競爭非常激烈的領域中以更優的收益風險比脫穎而出時，市場終將達到平衡。

Brian, what thoughts would you like to add to my comments?

布萊恩，還有什麼想補充的嗎？

Thanks, Troy. I think you captured it well, I think, but I want to maybe just add just a couple of points that -- the advantage I think right now that you're seeing, there's a one-year advantage in the market potentially, but it's a few weeks, five weeks at most advantage in the NPM1 space. Our teams are out there, as I mentioned. We've been engaging. We've been spending the last year working with payers to ensure that there is not going to be any kind of blocking available. And the profile of ziftomenib, I think, really has resonated where payers wouldn't see a need to do something like that.

謝謝你，特洛伊。我認為你已經很好地抓住了重點，但我可能只想補充幾點——我認為你現在看到的優勢，在市場上可能存在一年的優勢，但在 NPM1 領域，最多只有幾週或五週的優勢。正如我剛才提到的，我們的團隊就在那裡。我們一直在積極參與。過去一年，我們一直在與付款方合作，以確保不會出現任何形式的阻礙。我認為，ziftomenib 的療效確實引起了支付方的共鳴，他們原本認為沒有必要採取類似的措施。

So from an access perspective, we think that we'll have a very powerful, strong position in that space. Our goal is to build a distribution model that is seamless and easy for physicians and their practices to prescribe ziftomenib. One of the things that might be even more simplistic, as we talk about the simplicity, is that we'll have one SKU. We're not going to have multiple SKUs of different products that they have to worry about inventory and dosing challenges, things like that.

因此，從市場准入的角度來看，我們認為我們將在該領域擁有非常強大的地位。我們的目標是建立一個無縫且便利的經銷模式，讓醫生及其診所能夠輕鬆地開立 ziftomenib 處方。說到簡單性，還有一件可能更簡單的事情，那就是我們將只有一個 SKU。我們不會有多種不同產品的 SKU，讓他們擔心庫存和劑量方面的挑戰等等。

So there may be some advantages we think that we'll be able to capitalize on in the near term. But I just go back finally to say that the field team that we've hired has extensive experience with these practices. They are itching to be out there to speak about ziftomenib and they're ready to go. And I feel like that if you give us the time for launch, I think you'll see that the profile that Troy outlined and our ability to execute is going to be on par or better than anyone in the industry. So I'm very confident we'll have an opportunity to really overcome any second move or disadvantage that may be perceived.

因此，我們認為在短期內我們或許能夠利用一些優勢。最後我想說的是，我們聘請的現場團隊在這些方面擁有豐富的經驗。他們迫不及待地想要站出來談論齊夫托美尼，他們已經準備好了。我覺得，如果給我們足夠的時間進行推廣，你們就會看到，Troy 所描繪的藍圖以及我們的執行能力，將會達到甚至超過業內任何其他公司。所以我非常有信心，我們有機會真正克服任何可能出現的二次進攻或劣勢。

Thank you, Brian. That was great. Let me just add just a couple more thoughts, Jason, to your question. We are going to be promoting on labels. The label is going to be relapsed refractory and PM1 mutant AML, clearly, the adult population. But as we indicated in the prepared remarks and as you've seen, I think we have now the most comprehensive and I would argue the most aggressive overall development program. We have two Phase 3s underway in intensive and non-intensive. We're combining with both FLT3 inhibitors.

謝謝你，布萊恩。那很棒。傑森，關於你的問題，我還有幾點補充。我們將透過唱片公司進行推廣。標籤將為復發難治性 PM1 突變型 AML，顯然，指的是成人族群。但正如我們在準備好的演講稿中指出的，也正如你們所看到的，我認為我們現在擁有最全面、我認為也是最積極的整體發展計劃。我們正在進行兩個第三階段項目，分別是密集型和非密集型項目。我們正在將兩種 FLT3 抑制劑合併使用。

We have combinations with LDAC, with FLAG-IDA. And as Mollie said, we're coming forward not with a handful of patients. We're coming forward with 20, 30, 40, 70, 100 patients at a time. So we're really giving -- which is why I think we have two -- our two presentations at ASH are both orals. We have a massive development and medical affairs effort supporting our commercial launch. We won't be able to promote in those. We'll be publishing, we'll be educating, we'll be collaborating, but everyone is looking forward to combinations.

我們與 LDAC 和 FLAG-IDA 有組合。正如莫莉所說，我們並非只有少數患者站出來。我們一次會送來 20、30、40、70、100 名患者。所以我們真的在全力以赴——這也是為什麼我們在 ASH 上的兩個演講都是口頭報告的原因。我們投入了大量的研發和醫療事務力量來支持我們的商業化上市。我們將無法在那些地方晉升。我們將出版發行，我們將進行教育，我們將開展合作，但每個人都期待著各種組合的出現。

Everyone's looking forward to earlier lines of therapy. We're not looking at one quarter or even two quarters. Our goal is how do we make ziftomenib the cornerstone therapy throughout the treatment continuum. And I think we have the right strategy to do that. As Brian said, a few weeks coming behind isn't really going to make much of a difference at all. So appreciate the question.

大家都期待著更早進行治療。我們關注的不是一個季度，甚至不是兩個季度。我們的目標是如何使齊夫托美尼成為整個治療過程中的基石療法。我認為我們有正確的策略來實現這一目標。正如布萊恩所說，晚幾週其實根本不會造成什麼影響。非常感謝您的提問。

(Operator Instructions) Reni Benjamin, JMP Securities.

（操作員說明）Reni Benjamin，JMP Securities。

Congrats on all the progress. Thanks for taking the questions. I guess, Troy, you had mentioned in your prepared remarks regarding the joint launch meetings. I'd love to -- can you provide any sort of color in what goes on in these meetings, how many people, what's the split between you and KK? Do you hit the ground running as soon as you get approval? Do you wait until next year? Just any sort of color as to how this will move forward. Thanks.

祝賀你們取得的所有進展。謝謝您回答問題。我想，特洛伊，你在事先準備好的演講稿中提到了聯合發射會議。我很想了解－您能否詳細介紹一下這些會議的內容，例如有多少人參加，您和KK的參與比例是多少？一旦獲得批准，您是否立即開始工作？你打算等到明年嗎？任何能說明事情將如何發展的跡像都行。謝謝。

Yeah, Ren. Thanks for the question. This was the best launch meeting I've ever attended. It was electrifying. It really was. People are so excited to bring this therapy forward. But let me turn it over to Brian, who can maybe give you a bit more specificity about what the goals of the launch meeting were and how the two teams came together as 1K to really move this forward. Brian?

是的，任。謝謝你的提問。這是我參加過的最棒的新品發表會。真是令人興奮。確實如此。大家都很興奮能推動這項療法的實施。但讓我把麥克風交給布萊恩，他或許能更具體地說明啟動會議的目標是什麼，以及兩個團隊如何以 1K 的身份走到一起，真正推動這件事向前發展。布萊恩？

Yeah, sure. Thanks, Troy. Yeah, Reni, so this launch meeting, and as typically what you'll do as you prepare, is to bring the field teams together so that they're well-trained and ensure that they're ready to go in case we have an approval. Timing of a launch meeting, you can do them after you get approval, you can do them before. We tried to build a bit of a buffer where we thought October gives us an opportunity for the teams to be ready as close as possible to a potential approval.

當然可以。謝謝你，特洛伊。是的，雷尼，所以這次啟動​​會議，以及你通常在準備過程中會做的事情，就是把現場團隊聚集在一起，以便他們接受良好的培訓，並確保如果我們獲得批准，他們已經做好準備。關於發表會的召開時間，可以在獲得批准後召開，也可以在獲得批准前召開。我們試著留出一些緩衝時間，我們認為十月能讓各團隊有機會盡可能接近可能的批准做好準備。

And essentially, this is a team where we had all of the fields members that are both from Kyowa Kirin and from Kura, that not just for our sales organizations that are going to be working together. We'll have the two field forces are going to be putting their efforts towards raising awareness and selling ziftomenib to the target physicians, but they're basically -- we put that group together as well as our field market access teams, our field medical teams, and we spent several days just working through understanding the role of menin in AML, the challenges for patients with relapsed/refractory AML, did some certifications, pre-certifications for the team so they're ready to go and are prepared.

本質上，這是一個由協和麒麟和藏馬兩家公司的所有現場成員組成的團隊，他們不僅來自我們的銷售部門，而且將共同合作。我們將派出兩支現場銷售隊伍，致力於提高目標醫生對 ziftomenib 的認識並進行銷售。我們組建了這個團隊，包括我們的現場市場准入團隊和現場醫療團隊，並花了幾天時間深入了解 menin 在 AML 中的作用、復發/難治性 AML 患者面臨的挑戰，並為團隊進行了一些認證和預認證，以便他們隨時可以開始工作。

As soon as we get to an anticipated FDA approval, the teams will then recertify on that final prescribing information, and we'll be able to get out in the field immediately. We've been planning our organizational readiness in case of an early approval.

一旦我們獲得預期的 FDA 批准，團隊將對最終處方資訊進行重新認證，然後我們就可以立即投入使用。我們一直在製定組織方面的準備計劃，以應對可能提前獲得批准的情況。

So the teams, I can say, have been ready to go for at least since that meeting in October. And probably even before that, we had all the rest of our organizational readiness put together. So we've been trying to pull together that full team. And as Troy said, it was a really well-executed meeting between both companies, and there's a tremendous amount of energy and readiness for that anticipated approval as soon as by end of November as our target PDUFA date, we'll be ready to go.

所以可以說，各隊至少從十月份的那次會議以來就已經做好了準備。甚至可能在此之前，我們已經做好了所有其他組織的準備。所以我們一直在努力組建完整的團隊。正如 Troy 所說，這是兩家公司之間非常成功的會議，雙方都充滿了熱情和準備，期待在 11 月底（我們的目標 PDUFA 日期）獲得預期的批准，屆時我們將做好準備。

Peter Lawson, Barclays.

Peter Lawson，巴克萊銀行。

Hey guys, it's Alex, it's on for Peter. Thanks for taking our question. Just a quick one for me on what the label could look like. Is there any potential for the monitoring requirements for differentiation syndrome to be different from other AML drugs?

大家好，我是Alex，現在輪到Peter了。感謝您回答我們的問題。請您幫我快速看一下標籤可能的樣子。針對分化症候群的監測要求是否有可能與其他 AML 藥物有所不同？

Alex, you're asking -- let me make sure I'm reading your question back. Are you asking, is there going be a different -- potentially a difference in the monitoring requirements for DS in the label? Is that your question? Yeah. Molly, do you want to --?

Alex，你在問——讓我確認一下我是否理解了你的問題。您是想問，標籤中對DS的監測要求是否會有所不同嗎？這就是你的問題嗎？是的。莫莉，你想…——？

Yeah, or how to address it versus prior drugs. Yeah, thank you.

是的，或者說，如何應對它與先前藥物的差異。是啊，謝謝。

Yeah, absolutely. So obviously, I don't want to comment on ongoing discussions. We're still nearing our PDUFA date, and so obviously things are still evolving; however, our differentiation syndrome guidance has been laid out in our protocols and in our IB for years now, and it is unchanged. I don't think that it is any additional monitoring that would be unexpected for this patient population in general who is regularly getting labs tested, et cetera. But let's wait and see and have a more fulsome discussion once we actually have, hopefully, the approval in hand.

是的，絕對的。很顯然，我不想對正在進行的討論發表評論。我們距離 PDUFA 日期還有一段時間，所以很明顯情況仍在發展變化；但是，我們的分化綜合徵指南已經在我們的方案和 IB 中製定多年，並且沒有改變。我認為對於這部分患者群體來說，定期進行實驗室檢查等，進行額外的監測並不會出乎意料。但我們還是等等看，等真正拿到批准後再進行更全面的討論吧。

David Dai, UBS.

David Dai，瑞銀集團。

And I just want to come back to that, the market dynamics between you and the competitors. So Troy, I'm wondering, based on your pre-launch work you and Kyowa Kirin have been doing, could you maybe share some of the initial feedback from physicians on how they're viewing [ziftomenib's tolerability] versus the competitor's many inhibitors in the space, the [MPL1] space?

我想再回到你和競爭對手之間的市場動態這個問題。所以 Troy，我想問一下，根據你和 Kyowa Kirin 所做的上市前工作，你能否分享一些醫生對 [ziftomenib] 耐受性與該領域（[MPL1] 領域）競爭對手的眾多抑製劑相比的初步反饋？

Yeah, David. I'm going to ask Brian to speak to that. As you can imagine, we've done a lot of market research and sought the opinions of KOLs and practicing physicians. But Brian, maybe you can speak to the lessons learned thus far about ziftomenib’s profile relative to our competitors.

是的，大衛。我會請布萊恩談談這件事。正如您所想，我們進行了大量的市場調查，並徵求了關鍵意見領袖和執業醫生的意見。但布萊恩，或許你可以談談到目前為止，我們從 ziftomenib 的概況（相對於我們的競爭對手而言）中學到的經驗教訓。

Sure. Thank you, David, for that question. So I'll speak to the feedback we received and really kind of align it around four key parameters or pillars, you could call them. First is the efficacy. We've tested the profiles of ziftomenib relative to other potential menin inhibitor competition, and it seems that the view is that the efficacy is kind of a table stakes to get in.

當然。謝謝你，大衛，提出這個問題。所以，我會談談我們收到的回饋，並圍繞四個關鍵參數或支柱（你可以這樣稱呼它們）進行調整。首先是功效。我們已經測試了 ziftomenib 相對於其他潛在的 menin 抑制劑競爭對手的特性，結果顯示，療效似乎是進入該領域的必要條件。

You'll see that the CR/CRh, duration of response, things like that are seen to be relatively similar. Safety and tolerability is something that did stand out as a differentiator between ziftomenib and other products, which that alone, as Troy said, is not -- safety is not something that wins on a product, but it's that balance of benefit and risk and the tolerability of that. Really, things can tip the scales.

你會發現 CR/CRh、反應持續時間等指標都相對相似。安全性和耐受性確實是 ziftomenib 與其他產品的一個顯著區別，但正如 Troy 所說，這本身並不是決定性因素——安全性並不是一個產品獲勝的關鍵，而是收益與風險之間的平衡以及對這種平衡的耐受性。確實，一些因素可能會左右局勢。

The other two pillars around -- that we found really helped to differentiate ziftomenib is one around the combinability with current concomitant medications. As Troy mentioned, we're going to be focusing on our on-label use emotionally, which is going to be in that relapsed refractory monotherapy space. But those patients typically get concomitant meds like Azoles and others to manage the challenges of being a relapsed refractory AML patient. And the combinability and simplicity of a dose where you don't have to do a lot of modifications seems to be meaningful for physicians as well and for patients because it's more straightforward.

我們發現，真正有助於區分 ziftomenib 的另外兩個支柱是它與目前伴隨用藥的可組合性。正如 Troy 所提到的，我們將專注於情緒方面的標籤內使用，也就是復發難治性單藥治療領域。但這些患者通常會同時服用唑類藥物等藥物，以應對復發難治性 AML 患者所面臨的挑戰。而且，這種劑量組合簡單、無需進行太多調整的方案，對於醫生和患者來說似乎都很有意義，因為它更直接。

And then finally, the third was around simplicity. Once a day, daily dosing, there's one dose that each -- most patients or all patients really need is that 600-milligram dose is very straightforward and imagine for a NPM1 relapse refractory patient who is typically in the elderly population, the simplicity of having that once daily dose is also meaningful.

最後，第三個主題是簡潔。每日一次，每日給藥，每個患者——大多數患者或所有患者真正需要的劑量是 600 毫克，這非常簡單明了。想像一下，對於通常屬於老年族群的 NPM1 復發難治性患者來說，每日一次給藥的簡便性也意義重大。

So that's really what we've heard is that there are -- of course, we've also heard, as Troy said, any therapies for these patients are really going to be important that can deliver some efficacy. But when you have choices, that's when you start to parse out what those differences may be. And that's where we feel pretty confident in the profile of ziftomenib as a differentiative agent coming into the market.

所以，我們聽到的主要是——當然，正如特洛伊所說，我們也聽到，任何能夠對這些患者產生療效的療法都非常重要。但當你有選擇的時候，你就會開始仔細分析這些選擇之間的差異。正因如此，我們對 ziftomenib 作為一種具有差異化優勢的藥物進入市場充滿信心。

Li Wang Watsek, Cantor Fitzgerald.

李旺·瓦塞克，康托·菲茨杰拉德。

And I guess just given the recent disruptions at FDA, including within Sedar, I'm just curious, have you noticed or anticipate any changes in terms of cadence and discussions with agency?

鑑於 FDA 最近發生的一些混亂，包括 Sedar 內部的混亂，我很好奇，您是否注意到或預計在與該機構的溝通節奏和討論方面會有任何變化？

Short answer, Lee, we haven't noticed any difference. We don't anticipate any difference. We're on track for our November 30 PDUFA date. I think we characterized the interactions with the agency as open and constructive. We don't know what we don't know, but I think at this point, we feel like we're in good shape and we're tracking toward a positive review outcome.

簡而言之，李，我們沒有發現任何差異。我們預計不會有任何不同。我們正按計畫推進，將於11月30日提交PDUFA申請。我認為我們對與該機構的互動進行了開放和建設性的描述。我們不知道我們不知道什麼，但我認為目前我們感覺情況良好，正朝著正面的評價結果邁進。

The path to approval in AML is much better precedented than some of these other instances. The fact that we have a competitor who was just approved in the same indication just a few weeks before, I think gives us good confidence that we're on track. But obviously, we'll continue to stay vigilant. And Mollie and her regulatory team are doing a terrific job. But so far, it's all systems are go.

與其他一些領域相比，反洗錢領域的審批流程有更完善的先例可循。就在幾週前，我們的競爭對手剛剛在同一適應症領域獲得批准，我認為這讓我們更有信心，我們正走在正確的道路上。但很顯然，我們會繼續保持警覺。莫莉和她的監管團隊做得非常出色。但目前為止，一切進展順利。

There are no further questions at this time. So I would now like to turn the call back over to Troy Wilson for our closing remarks. Thank you.

目前沒有其他問題了。現在我謹將電話交還給特洛伊·威爾遜，請他作總結發言。謝謝。

Thank you, Dani. Thank you all once again for joining the call today and for your questions and the discussion. We'll be participating in the Jefferies Investor Conference in London later this month. And just as a reminder, we'll also be hosting a virtual analyst and investor event on December 8 at the ASH Annual Meeting in Orlando. So we'll look forward to speaking with many of you at these events. As we move forward, our focus remains on executing with discipline, investing wisely, and advancing a pipeline designed to make a real difference for patients.

謝謝你，丹妮。再次感謝各位今天參加電話會議，感謝你們提出的問題和參與討論。本月晚些時候，我們將參加在倫敦舉行的傑富瑞投資者大會。另外提醒大家，我們也將在 12 月 8 日於奧蘭多舉行的 ASH 年會上舉辦一場虛擬分析師和投資者活動。所以我們期待在這些活動中與大家交流。展望未來，我們將繼續專注於嚴謹執行、明智投資，並推動旨在為患者帶來真正改​​變的研發管線。

With our pipeline, our experienced, passionate team, and a strong balance sheet, we think we're well-positioned to deliver long-term value for both our patients and our shareholders. Until our next update. If you have any additional questions, you know how to find us. Please reach out. Thank you all once again, and we hope you all have an enjoyable Tuesday morning and a productive day.

憑藉我們的研發管線、經驗豐富、充滿熱情的團隊以及穩健的資產負債表，我們認為我們有能力為患者和股東創造長期價值。下次更新見。如果您還有其他問題，您知道如何找到我們。請聯絡我們。再次感謝大家，祝大家週二上午愉快，工作順利。

With that, we'll adjourn the call. Thanks, everyone.

至此，我們將結束通話。謝謝大家。