Karyopharm Therapeutics Inc (KPTI) 2025 Q2 法說會逐字稿

Good morning. My name is Ludy, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics second-quarter 2025 financial results conference call. (Operator Instructions) Please be advised that this call is being recorded at the company's request.

早安.我叫 Ludy，今天我將擔任您的會議主持人。現在，我歡迎大家參加 Karyopharm Therapeutics 2025 年第二季財務業績電話會議。（操作員指示）請注意，此通話是應公司要求錄音的。

I would now like to turn the conference over to Brendan Strong, Senior Vice President, Investor Relations and Corporate Communications. Please go ahead.

現在，我想將會議交給投資者關係和企業傳播高級副總裁 Brendan Strong。請繼續。

Good morning. Thank you for joining us on today's conference call to discuss Karyopharm's second-quarter 2025 financial results and recent company progress. We issued a press release this morning detailing our financial results for the second quarter of 2025. This release, along with a slide presentation that we will reference during our call today, are available on our website.

早安.感謝您參加今天的電話會議，討論 Karyopharm 2025 年第二季的財務表現和公司近期進展。我們今天上午發布了一份新聞稿，詳細介紹了我們 2025 年第二季的財務表現。此新聞稿以及我們今天電話會議中將參考的幻燈片演示均可在我們的網站上找到。

For today's call, as seen on slide 2, I'm joined by Richard, Reshma, Sohanya, and Lori, who'll provide an update on our results for the second quarter of 2025 and discuss recent clinical developments.

如投影片 2 所示，在今天的電話會議中，Richard、Reshma、Sohanya 和 Lori 將與我一起介紹我們 2025 年第二季的業績更新，並討論最近的臨床發展。

Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995 as outlined on slide 3. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent Form 10-Q or 10-K on file with the SEC and in other filings that we may make with the SEC in the future.

在我們開始正式評論之前，我要提醒您，我們今天發表的各種言論均構成《1995 年私人證券訴訟改革法》安全港條款規定的前瞻性陳述，如幻燈片 3 所示。由於各種重要因素，實際結果可能與這些前瞻性陳述所示的結果有重大差異，包括我們向美國證券交易委員會提交的最新 10-Q 或 10-K 表格中的風險因素部分以及我們將來可能向美國證券交易委員會提交的其他文件中討論的因素。

Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any later date.

任何前瞻性陳述僅代表我們截至今天的觀點。雖然我們可能選擇在未來某個時間點更新這些前瞻性陳述，但我們明確表示不承擔任何義務，即使我們的觀點改變。因此，您不應依賴這些前瞻性陳述來代表我們以後的觀點。

I'll now turn the call over to Richard. Please turn to slide 4.

我現在將電話轉給理查德。請翻到幻燈片 4。

Thank you, Brendan, and thank you all for joining us today for Karyopharm's Q2 2025 earnings call. Before we begin, as outlined on slide 5, I want to address a topic that is on the minds of our employees, our partners, and our investors.

謝謝你，布倫丹，也謝謝大家今天參加 Karyopharm 2025 年第二季財報電話會議。在我們開始之前，正如幻燈片 5 所述，我想談談我們的員工、合作夥伴和投資者關心的一個主題。

We are operating in a period of financial constraints with a near-term debt maturity in October. We are actively engaged with our lenders and advisers to enhance our liquidity and maximize value.

我們正處於財務緊張時期，近期債務將於十月到期。我們積極與貸方和顧問合作，以增強我們的流動性並實現價值最大化。

Importantly, the fundamentals of our business remain strong with a profitable multi-myeloma commercial organization that provides us with a solid foundation that we can build on with two potentially transformative Phase 3 readouts expected over the next 12 months. These trials target diseases where patients have few treatment options and there is an opportunity to improve on existing therapies.

重要的是，我們業務的基本面依然強勁，我們擁有一個盈利的多發性骨髓瘤商業組織，這為我們提供了堅實的基礎，我們可以在此基礎上繼續發展，預計在未來 12 個月內將出現兩個具有變革意義的 3 期結果。這些試驗針對的是患者治療選擇很少的疾病，並且有機會改善現有的治療方法。

Based on the strength of our data to date, we believe we have the potential to redefine the standard of care for these patients. This is the value that we are building towards and what drives our confidence in the long-term trajectory of the company.

根據我們迄今為止的數據實力，我們相信我們有潛力重新定義這些患者的照護標準。這是我們正在努力實現的價值，也是我們對公司長期發展方向充滿信心的動力。

With that, let's get into our results for the quarter, where we delivered solid commercial results and made exciting progress towards enrolling our pivotal Phase 3 trials in myelofibrosis and endometrial cancer. I am pleased to report that we expect to close new patient screening this week in our Phase 3 SENTRY trial in patients with JAK-naive myelofibrosis.

讓我們來看看本季度的業績，我們取得了穩健的商業業績，並在開展骨髓纖維化和子宮內膜癌關鍵性 3 期試驗方面取得了令人興奮的進展。我很高興地報告，我們預計本週結束針對 JAK 初治骨髓纖維化患者的 3 期 SENTRY 試驗的新患者篩選。

This is a major milestone that is a result of many years of hard work and dedication from people throughout our organization and I thank all of our teams. We greatly thank the patients and clinical trial sites that are participating in SENTRY.

這是一個重要的里程碑，也是我們整個組織人員多年來辛勤工作和奉獻的結果，我感謝我們所有的團隊。我們非常感謝參與 SENTRY 的患者和臨床試驗站點。

Importantly, SENTRY will be our first Phase 3 trial readout where we utilize a lower dose of selinexor combined with antiemetics during the first two cycles of treatment to improve the tolerability of selinexor as we work to enhance the patient experience. Through our strong clinical trial execution, we are seeing the benefits of both of these factors in the preliminary blinded safety data that Reshma will review to date. We are eagerly anticipating top line data in March of 2026.

重要的是，SENTRY 將是我們的第一個 3 期試驗讀數，我們將在前兩個治療週期中使用較低劑量的 selinexor 聯合止吐藥，以提高 selinexor 的耐受性，同時努力改善患者體驗。透過我們強有力的臨床試驗執行，我們在 Reshma 迄今為止審查的初步盲法安全數據中看到了這兩個因素的好處。我們熱切期待 2026 年 3 月的頂線數據。

Turning to slide 6. Completing enrollment in our Phase 3 SENTRY trial is an important step on our over seven-year journey to demonstrate the role that XPO1 inhibition may play in patients with myelofibrosis. The Phase 3 trial caps a growing body of evidence that has consistently demonstrated the potential for XPO1 in myelofibrosis. We are optimistic about the potential for selinexor plus ruxolitinib to redefine the standard of care for patients living with this disease and pending positive data, the transformational opportunity this represents for our organization.

翻到幻燈片 6。完成我們 3 期 SENTRY 試驗的招募是我們七年多來證明 XPO1 抑制在骨髓纖維化患者中可能發揮的作用的重要一步。這項 3 期試驗總結了越來越多的證據，這些證據一致證明了 XPO1 在治療骨髓纖維化方面的潛力。我們對 selinexor 和 ruxolitinib 重新定義患有這種疾病的患者的護理標準的潛力以及即將獲得的積極數據以及這對我們組織代表的轉型機會感到樂觀。

As outlined on slide 7, given the opportunity to improve the standard of care, leading KOLs, including Dr. John Mascarenhas from Mount Sinai, who is the principal investigator for SENTRY, continue to highlight the need for new treatment options for patients with myelofibrosis. The depth and durability of response that Dr. Mascarenhas mentioned in a recent interview with a patient advocacy organization plays to the strength of selinexor.

如投影片 7 所述，鑑於有機會提高護理標準，領先的 KOL（包括 SENTRY 首席研究員、西奈山的 John Mascarenhas 博士）繼續強調對骨髓纖維化患者進行新治療選擇的需求。Mascarenhas 博士在最近接受患者權益組織採訪時提到的反應深度和持久性充分體現了 selinexor 的優勢。

Finally, as shown on slide 8, we estimate the peak revenue potential for selinexor in myelofibrosis is up to approximately $1 billion annually in the US alone and believe that commercial uptake would be rapid. We are very eager to bring this combination therapy to the market, pending the outcome of our data and future regulatory approvals.

最後，如幻燈片 8 所示，我們估計僅在美國，selinexor 在治療骨髓纖維化方面的峰值收入潛力就高達每年約 10 億美元，並且相信商業化應用將會很快。我們非常渴望將這種聯合療法推向市場，等待我們的數據結果和未來監管部門的批准。

Now I'd like to turn the call over to Reshma.

現在我想把電話轉給 Reshma。

Thank you, Richard. I will be sharing new blinded preliminary safety data with you today from our Phase 3 SENTRY trial that may support the potential of the combination of selinexor plus ruxolitinib, which may have a similar, if not more favorable safety profile than ruxolitinib alone. Before I get into the new data, let's review why we believe selinexor as an XPO1 inhibitor is a rational mechanism to evaluate in patients with myelofibrosis, starting on slide 10.

謝謝你，理查。今天，我將與您分享我們 3 期 SENTRY 試驗的新的盲法初步安全數據，這些數據可能支持 selinexor 與 ruxolitinib 聯合使用的潛力，其安全性可能與單獨使用 ruxolitinib 相似，甚至更佳。在介紹新數據之前，讓我們先回顧為什麼我們認為 selinexor 作為 XPO1 抑制劑是評估骨髓纖維化患者的合理機制，從投影片 10 開始。

Selinexor prevents the nuclear export of various proteins and messenger RNA molecules, thus inhibiting both JAK and non-JAK pathways. The latter, which includes the nuclear localization and activation of p53, an important tumor suppressor in myelofibrosis, given that approximately 95% of myelofibrosis patients are p53 wild-type.

Selinexor 可阻止各種蛋白質和信使 RNA 分子的核輸出，進而抑制 JAK 和非 JAK 路徑。後者包括 p53 的核定位和激活，p53 是骨髓纖維化中的重要腫瘤抑制因子，因為大約 95% 的骨髓纖維化患者都是 p53 野生型。

As Richard indicated, we believe that the combination of selinexor plus ruxolitinib has the potential to establish a new treatment paradigm for myelofibrosis patients by addressing each of the four key pillars of this disease as outlined on slide 11. While no assurances can be given, our confidence continues to strengthen as we receive and review additional data, including updated blinded safety data that I will be reviewing shortly.

正如理查德所指出的，我們相信，selinexor 與 ruxolitinib 的組合有可能透過解決幻燈片 11 中概述的這種疾病的四個關鍵支柱，為骨髓纖維化患者建立新的治療模式。雖然無法做出任何保證，但隨著我們收到並審查更多數據（包括我將很快審查的更新的盲法安全數據），我們的信心不斷增強。

To set the stage, there has been a lack of new treatment options given that JAK inhibitors are the only approved class of therapies. Ruxolitinib has been the standard of care for over 13 years. As the potential first combination therapy in myelofibrosis, selinexor plus ruxolitinib would be a convenient all oral therapy that the myelofibrosis community has clearly indicated interest in adopting given the rapid, deep, and durable spleen reductions and symptom improvement observed from the Phase 1 study.

首先，由於JAK抑制劑是唯一核准的治療類型，因此缺乏新的治療選擇。魯索替尼已成為治療標準超過 13 年。作為骨髓纖維化的潛在首個聯合療法，selinexor 加 ruxolitinib 將是一種方便的全口服療法，鑑於第一階段研究觀察到的脾臟快速、深度和持久縮小以及症狀改善，骨髓纖維化社區已明確表示有興趣採用該療法。

Let's now focus on the four key hallmarks in myelofibrosis. First, spleen volume reduction. I think it is a very helpful reminder that only approximately one-third of patients achieved a spleen volume reduction of greater than 35% with ruxolitinib alone. Our Phase 1 data suggests that the combination could more than double the SVR35 rate with durable responses also seen.

現在讓我們專注於骨髓纖維化的四個主要特徵。一是脾臟體積縮小。我認為這是一個非常有用的提醒，只有大約三分之一的患者僅透過單獨使用蘆可替尼就實現了脾臟體積減少 35% 以上。我們的第一階段數據表明，該組合可使 SVR35 率提高一倍以上，並且還會出現持久的反應。

Second is symptom improvement. Data from our Phase 1 trial of selinexor in combination with ruxolitinib showed an average 18.5 point improvement in absolute TSS at week 24, which suggests this combination could provide a meaningful improvement over the 11- to 14-point improvement achieved by patients on ruxolitinib as observed in the Phase 3 MANIFEST-2 and TRANSFORM-1 trials.

二是症狀改善。我們進行的 selinexor 與蘆可替尼聯合治療的 1 期試驗數據顯示，第 24 週時絕對 TSS 平均改善了 18.5 分，這表明這種聯合治療可以帶來比蘆可替尼患者在 3 期 MANIFEST-2 和 TRANSFORM-1 試驗中觀察到的 11 至 14 分的改善更顯著的改善。

Third is hemoglobin stabilization and transfusion burden. The data that we presented in June at EHA show higher hemoglobin levels, lower transfusion burden in much lower rates of all grade in grade 3-plus anemia in myelofibrosis patients previously treated with JAK inhibitor therapies who were randomized to selinexor compared to the physician's choice arm, which included retreatment with the JAK inhibitor therapies, including ruxolitinib.

第三是血紅素穩定和輸血負擔。我們 6 月在 EHA 上發表的數據顯示，在接受 JAK 抑制劑治療的骨髓纖維化患者中，與醫生選擇組（包括接受包括蘆可替尼在內的 JAK 抑制劑療法再治療）相比，隨機接受 selinexor 治療的患者血紅蛋白水平更高、輸血負擔更低、3 級及以上貧血的發生率更低。

Fourth is disease modification. There is minimal evidence of disease modification with JAK inhibitors. Data observed from selinexor monotherapy studies in a pretreated myelofibrosis population as well as our Phase 1 combination data in JAK inhibitor naive myelofibrosis, suggest meaningful reductions in key cytokines that are critical to myelofibrosis pathogenesis, symptom development, and anemia; as well as improvements in bone marrow fibrosis, increases in erythroid progenitors, and mutational burden.

第四是疾病改良。JAK 抑制劑對病情改善的效果極小。在接受過治療的骨髓纖維化人群中進行的 selinexor 單藥治療研究以及我們在 JAK 抑製劑初治骨髓纖維化中的 I 期聯合用藥數據表明，對骨髓纖維化發病機制、症狀發展和貧血至關重要的關鍵細胞因子顯著減少；骨髓纖維化得到改善，紅系祖細胞增加，突變負擔減輕。

Turning to slide 12. We are pleased that our Phase 3 SENTRY trial will be closing new patients screening this week. Importantly, based upon an initial review of the baseline characteristics of the patients enrolled to date, they are representative of the intended patient population.

翻到第 12 張投影片。我們很高興我們的第三階段 SENTRY 試驗將於本週結束新患者篩檢。重要的是，根據對迄今為止入組患者基線特徵的初步審查，他們代表了目標患者群體。

One notable characteristic is the baseline TSS, which when excluding fatigue, may ultimately be higher than other Phase 3 trials; an important trend that may suggest that our trial could be well positioned to report a greater improvement in absolute TSS. In this new era of combination therapies, there have been challenges demonstrating meaningful symptom improvement above and beyond ruxolitinib.

一個顯著的特徵是基線 TSS，當排除疲勞時，最終可能高於其他 3 期試驗；這一重要趨勢可能表明我們的試驗可以很好地報告絕對 TSS 的更大改善。在這個聯合治療的新時代，證明其能比蘆可替尼更有效地改善症狀一直是個挑戰。

Based upon learnings from other trials, we believe we have optimized SENTRY for success. First, we changed the co-primary endpoint of TSS50 to absolute TSS, a more sensitive method by which to detect meaningful symptom improvement above and beyond ruxolitinib.

根據其他試驗的經驗，我們相信我們已經優化了 SENTRY 並取得了成功。首先，我們將 TSS50 的共同主要終點改為絕對 TSS，這是一種更敏感的方法，可以檢測出超越蘆可替尼的有意義的症狀改善。

Second, we have excluded the fatigue domain and the primary analysis of absolute TSS in alignment with the US FDA due to the difficulty in accurately assessing changes in this symptom. We are certainly not the first to exclude fatigue.

其次，由於難以準確評估這種症狀的變化，我們根據美國 FDA 的規定排除了疲勞領域和絕對 TSS 的主要分析。我們當然不是第一個排除疲勞的人。

In fact, both the pivotal trials that led to ruxolitinib and fedratinib approvals also excluded fatigue in their TSS50 analyses. It's also important to keep in mind that all of our studies have excluded fatigue and symptom analysis, including our Phase 1 study evaluating the combination of selinexor and ruxolitinib, as well as MSO35, which evaluated selinexor as a monotherapy in previously treated MF patients.

事實上，導致魯索替尼和 fedratinib 獲得批准的兩個關鍵試驗也在 TSS50 分析中排除了疲勞。還需要記住的是，我們所有的研究都排除了疲勞和症狀分析，包括評估 selinexor 和 ruxolitinib 組合的第 1 階段研究，以及 MSO35，後者評估了 selinexor 作為先前接受過治療的 MF 患者的單一療法。

Finally, absolute TSS in the Phase 3 SENTRY trial will be analyzed using the mixed models repeated measure approach or MMRM. This differs from our Phase 1, which given the limitations in sample size, could only evaluate the mean or average change at week 24. MMRM is viewed as a more sensitive and potentially more robust method by which to analyze absolute TSS.

最後，將使用混合模型重複測量方法或 MMRM 分析第 3 階段 SENTRY 試驗中的絕對 TSS。這與我們的第一階段不同，由於樣本量的限制，第一階段只能評估第 24 週的平均變化。MMRM 被視為一種分析絕對 TSS 的更敏感且可能更穩健的方法。

The co-primary endpoints in SENTRY are SVR35 in absolute TSS, which are tested sequentially. Some of the key secondary and exploratory endpoints that will also be analyzed include progression-free survival, overall survival, hemoglobin stabilization, variant allele frequency reduction, improvement in bone marrow fibrosis, and changes in cytokine levels.

SENTRY 中的共同主要終點是絕對 TSS 中的 SVR35，它們是按順序測試的。也將分析一些關鍵的次要和探索性終點，包括無惡化存活期、整體存活期、血紅蛋白穩定性、變異等位基因頻率降低、骨髓纖維化的改善以及細胞激素水平的變化。

Now, let's review the encouraging preliminary blinded aggregate safety data from this trial. As these are preliminary data, please keep in mind that these data may not be reflective of the trial's actual top line results.

現在，讓我們回顧一下這次試驗令人鼓舞的初步盲法整體安全數據。由於這些是初步數據，請記住這些數據可能無法反映試驗的實際頂線結果。

The data on slides 13 and 14 are from the first 61 patients that enrolled in the Phase 3 portion of the SENTRY that have now been followed for a median of over 12 months. These patients were included in the successfully passed futility analysis conducted in the beginning of the year.

投影片 13 和 14 的數據來自參加 SENTRY 第 3 階段的前 61 名患者，這些患者的追蹤時間中位數現已超過 12 個月。這些患者被納入了年初進行的成功通過的無效性分析中。

While only members of the DSMB had access to the unblinded efficacy and safety data from these patients, we have continued to track the safety events over time and took a snapshot of the blinded safety data from these 61 patients on July 1, 2025, which continued to look favorable.

雖然只有 DSMB 成員才能存取這些患者未盲化的療效和安全性數據，但我們一直在持續追蹤安全事件，並於 2025 年 7 月 1 日對這 61 名患者的盲化安全性數據進行了快照，結果仍然令人滿意。

Let's start by reviewing the adverse event summary on the left side of slide 13. The data on the 61 patients shown in the table include patients randomized to either the combination of selinexor plus ruxolitinib or ruxolitinib in a 2:1 ratio. Because these are blinded data, we do not know the rates by each arm.

我們先來回顧第 13 張投影片左側的不良事件摘要。表中顯示的 61 名患者的數據包括以 2:1 的比例隨機分配接受 selinexor 加 ruxolitinib 或 ruxolitinib 組合治療的患者。因為這些是盲數據，所以我們不知道每個組別的比率。

The second and third columns provide the treatment emergent adverse event summary, or TEAE summary, following a median follow-up of more than 7 months or 12 months, respectively. What you see in the summary is that many of the adverse events occur early, with no meaningful increase in rates after the median of seven months of follow-up.

第二列和第三列分別提供了中位追蹤時間超過 7 個月或 12 個月後的治療出現的不良事件摘要或 TEAE 摘要。您在摘要中看到，許多不良事件發生得很早，經過中位數七個月的追蹤後，發生率並沒有顯著增加。

In an effort to improve comparability, we then took our analysis one step further. Knowing that the 61 patients were randomized 2:1, we use the historical data on ruxolitinib to extrapolate the preliminary safety data for the approximately 40 patients that received the combination, which is shown in the blue boxes on the right side of the slide.

為了提高可比性，我們進一步進行了分析。已知 61 名患者以 2:1 的比例隨機分配，我們使用蘆可替尼的歷史數據來推斷接受該組合治療的約 40 名患者的初步安全數據，如幻燈片右側的藍色框所示。

As you can see, the percentage of patients that have had at least one TEAE is approximately 97%, similar to what has been described for ruxolitinib. However, when we focus on the grade 3-plus TEAEs, the extrapolated data suggests that the rate may be slightly lower for patients on the combination versus ruxolitinib at approximately 53% and 57%, respectively.

如您所見，出現過至少一次 TEAE 的患者比例約為 97%，與蘆可替尼的描述相似。然而，當我們關注 3 級及以上 TEAE 時，推斷的數據表明，合併用藥患者的發生率可能略低於蘆可替尼組患者，分別約為 53% 和 57%。

Looking at serious TEAEs, the extrapolated data suggests an even greater benefit for the combination therapy than ruxolitinib. Finally, the extrapolated rate of TEAEs leading to treatment discontinuation is only 5% to 7% for the combination, lower than 6% to 11% range that has been historically reported for ruxolitinib, which we view as an encouraging observation.

從嚴重的 TEAE 來看，推斷的數據表明聯合治療比蘆可替尼具有更大的益處。最後，對於合併用藥，導致治療中斷的 TEAE 外推率僅為 5% 至 7%，低於歷史上報告的蘆可替尼 6% 至 11% 的範圍，我們認為這是一個令人鼓舞的觀察結果。

Let's turn to the individual treatment emergent adverse events, as shown on slide 14. We took the same approach with these data as the ones I just described on the prior slide.

讓我們來看看個別治療中出現的不良事件，如幻燈片 14 所示。我們對這些數據採取了與我在上一張投影片中描述的方法相同的方法。

Starting on the left, you'll see the all-grade blinded safety data on the 61 patients with a median follow-up of more than seven months and again for more than 12 months. We also show two noteworthy grade 3/4 TEAEs at the bottom left, anemia and thrombocytopenia.

從左側開始，您將看到 61 名患者的全級別盲法安全性數據，平均追蹤時間超過 7 個月，並且再次超過 12 個月。我們也在左下角顯示了兩種值得注意的 3/4 級 TEAE，即貧血和血小板減少症。

Consistent with what I described on the prior slide, we see most TEAEs occurring within the first seven months of follow-up. Additional events are observed with the passage of time, resulting in the rates of TEAEs modestly increased at 12 months of follow-up.

與我在上一張投影片中所描述的一致，我們發現大多數 TEAE 發生在追蹤的前七個月內。隨著時間的推移，觀察到了更多事件，導致 12 個月的追蹤中 TEAE 的發生率略有增加。

The number that excites me the most is the extrapolated rate of grade 3/4 anemia. At approximately 26%, the extrapolated rate of Grade 3/4 anemia for the combination is meaningfully lower than the 37% historically reported for ruxolitinib. And while the extrapolated rate of all grade nausea is higher in the combination arm than ruxolitinib, the approximately 64% is substantially lower than the approximately 80% rate that we reported in the Phase 1 portion of this trial.

最讓我興奮的數字是3/4級貧血的推論率。該組合的 3/4 級貧血外推發生率約為 26%，明顯低於魯索替尼歷史報告的 37%。雖然合併治療組所有噁心的推論發生率高於蘆可替尼組，但約 64% 的發生率明顯低於我們在該試驗第 1 階段報告的約 80% 的發生率。

We have recently presented compelling cytokine data that could explain in part the efficacy absorbed with selinexor. In addition, slide 15 shows pictographs of bone marrows evaluated at baseline and at week 24 from a patient treated with the selinexor ruxolitinib combination, and is further evidence of the potential disease modification that selinexor may induce in patients with myelofibrosis.

我們最近提供了令人信服的細胞激素數據，可以部分解釋 selinexor 所吸收的功效。此外，幻燈片 15 展示了接受 selinexor 蘆可替尼組合治療的患者在基線和第 24 週評估的骨髓象形圖，這進一步證明了 selinexor 可能在骨髓纖維化患者中誘發潛在的病情改變。

These data were first presented by Dr. Harris Ali at the International Congress of Myeloproliferative Neoplasms in October of 2024. This JAK inhibitor naive myelofibrosis patient was treated with selinexor 60 milligrams and ruxolitinib 15 milligrams twice a day as per the USPI.

這些數據最初由哈里斯·阿里博士於 2024 年 10 月在國際骨髓增生性腫瘤大會上發表。該名未接受 JAK 抑制劑治療的骨髓纖維化患者依照 USPI 每天接受兩次 60 毫克 selinexor 和 15 毫克 ruxolitinib 治療。

Due to cytopenias, the ruxolitinib dose was decreased to suboptimal ruxolitinib doses five milligrams twice a day starting in cycle two. The patient achieved an SVR35 as early as week 12 and a TSS50 as early as week eight as a result of symptom reduction from a baseline of 42 points to 19.5 points at week eight.

由於血球減少，從第二週期開始，蘆可替尼劑量減少至次優劑量，即每天兩次，每次五毫克。由於症狀從基線時的 42 分減少到第八週時的 19.5 分，患者早在第 12 週就達到了 SVR35，並在第八週就達到了 TSS50。

The efficacy observed in this patient can be explained in part by the meaningful change occurring in their bone marrow, specifically a 46% reduction in fiber density assessed by digital pathology was observed at week 24 compared to baseline samples; as was an approximately 200% increase in erythroid progenitors, which are precursors of mature red blood cells. While this is a single patient experience, the increase in erythroid progenitors could also explain the potentially lower grade 3-plus anemia rates with the combination as compared to historical ruxolitinib data as I explained on the previous slide.

該患者所觀察到的療效可以部分解釋為其骨髓中發生的有意義的變化，具體而言，與基線樣本相比，第 24 週時透過數位病理學評估發現纖維密度降低了 46%；紅血球祖細胞（成熟紅血球的前體）增加了約 200%。雖然這只是單一患者的經歷，但紅系祖細胞的增加也可以解釋與歷史魯索利替尼數據相比，聯合用藥後 3 級以上貧血發生率可能較低，正如我在上一張幻燈片中解釋的那樣。

We are very encouraged about these data and what it could mean for patients if we see something similar in the top line results in the Phase 3 SENTRY trial. Specifically, it could suggest a combination therapy that has a safety profile similar if not potentially better than standard-of-care ruxolitinib.

我們對這些數據感到非常鼓舞，如果我們在第 3 階段 SENTRY 試驗的頂線結果中看到類似的情況，這對患者來說意味著什麼。具體來說，它可以建議一種聯合療法，其安全性與標準治療魯索利替尼相似，甚至可能更好。

Given that both grade 3-plus anemia and thrombocytopenia are the same, if not better, than ruxolitinib alone, it could also suggest decreased blood draws for the patient and reduced monitoring burden for physicians and healthcare staff.

鑑於 3 級以上貧血和血小板減少症與單獨使用蘆可替尼的效果相同（甚至更好），這也可能意味著減少患者的抽血次數並減輕醫生和醫護人員的監測負擔。

I would also like to provide an update on our Phase 2 SENTRY-2 trial, where we are evaluating selinexor as a monotherapy in JAK inhibitor-naive myelofibrosis patients with moderate thrombocytopenia. Enrollment in this trial has been slower than anticipated, given that the vast majority of sites enrolling on SENTRY-2 are also enrolling patients into SENTRY and we have asked sites to prioritize enrollment on SENTRY.

我還想提供我們第 2 階段 SENTRY-2 試驗的最新進展，我們正在評估 selinexor 作為單一療法治療患有中度血小板減少症的 JAK 抑製劑初治骨髓纖維化患者。由於絕大多數參加 SENTRY-2 試驗的站點也在招募 SENTRY 患者，並且我們已要求站點優先在 SENTRY 上招募患者，因此本次試驗的招募速度比預期的要慢。

In addition, patients with platelet counts between 50,000 and 100,000 represents only 10% to 15% of all JAK-naive myelofibrosis. Now that SENTRY enrollment is completed, we plan on expanding the enrollment criteria to include all patients with platelet counts above 50,000, pending they meet all other eligibility criteria. This should increase the number of patients that can participate in this trial.

此外，血小板計數在 50,000 至 100,000 之間的患者僅佔所有 JAK 初治骨髓纖維化患者的 10% 至 15%。現在 SENTRY 招募已經完成，我們計劃擴大招募標準，將所有血小板計數超過 50,000 的患者納入其中，但前提是他們符合所有其他資格標準。這應該會增加可以參與該試驗的患者數量。

Our prior plan was to report preliminary data on a subset of patients from SENTRY-2 in the first half of this year. Given the enrollment challenges and the changes we are making to the enrollment criteria, we now plan to report top line data from all patients that we enroll in the 60-milligram cohort of this trial in 2026.

我們之前的計劃是在今年上半年報告 SENTRY-2 部分患者的初步數據。鑑於入組挑戰以及我們對入組標準所做的更改，我們現在計劃報告 2026 年參加該試驗 60 毫克組的所有患者的頂線數據。

Now, let's shift our focus to endometrial cancer, where p53 wild-type is such an important biomarker. As seen on slide 17, patients with both MMR proficient and TP53 wild-type tumors make up approximately 50% of all advanced or recurrent endometrial cancer cases, representing a very sizable group.

現在，讓我們將注意力轉移到子宮內膜癌，其中 p53 野生型是重要的生物標記。如幻燈片 17 所示，同時患有 MMR 功能正常和 TP53 野生型腫瘤的患者佔所有晚期或復發性子宮內膜癌病例的約 50%，這是一個非常龐大的群體。

Enrollment in the XPORT-EC-042 trial is progressing steadily as seen on slide 18, and we continue to expect to report top line data in the middle of 2026. I remain encouraged with the potential of selinexor to achieve clinically meaningful outcomes in the maintenance setting for patients with p53 wild-type endometrial cancer.

如第 18 頁投影片所示，XPORT-EC-042 試驗的招募工作正在穩步推進，我們預計將在 2026 年中期報告頂線數據。我仍然對 selinexor 在 p53 野生型子宮內膜癌患者的維持治療中取得具有臨床意義的結果的潛力感到鼓舞。

Lastly, our Phase 3 EMN29 SPd trial is outlined on slide 20. This trial aims to demonstrate the potential of an all-oral triplet treatment option for multiple myeloma patients that could also benefit those undergoing pre- and post T-cell engaging therapies. We expect to report top line data from this event-driven trial in the first half of 2026.

最後，我們的第 3 階段 EMN29 SPd 試驗概述於投影片 20。該試驗旨在證明全口服三重療法對多發性骨髓瘤患者的潛力，該療法也可使接受 T 細胞介導療法前後治療的患者受益。我們預計在 2026 年上半年報告此事件驅動試驗的頂線資料。

I will now turn the call to Sohanya.

現在我會把電話轉給 Sohanya。

Thank you, Reshma. On slide 22, I will discuss our commercial highlights for Q2 2025. XPOVIO net product revenue was $29.7 million this quarter, up 6% from the second quarter of 2024. Demand for XPOVIO was consistent in the second quarter of 2025 versus the second quarter of 2024, with the community setting continuing to drive approximately 60% of total US sales.

謝謝你，Reshma。在第 22 張投影片上，我將討論 2025 年第二季的商業亮點。XPOVIO 本季淨產品營收為 2,970 萬美元，較 2024 年第二季成長 6%。2025 年第二季與 2024 年第二季相比，XPOVIO 的需求保持一致，社區環境持續推動美國總銷售額的約 60%。

As we all know, the multiple myeloma market is highly competitive and is becoming more competitive each year. Within this market, XPOVIO is positioned in the community as a flexible therapy with a differentiated mechanism of action, oral convenient option following treatment with an anti-CD38 therapy, as well as in patients who cannot access or fail a T-cell engaging therapy. In the academic setting, XPOVIO is being increasingly used before and following T-cell therapies.

眾所周知，多發性骨髓瘤市場競爭非常激烈，而且每年的競爭都愈發激烈。在這個市場中，XPOVIO 被定位為一種具有差異化作用機制的靈活療法，是抗 CD38 療法治療後的便捷口服選擇，也適用於無法獲得 T 細胞介導療法或 T 細胞介導療法治療失敗的患者。在學術領域，XPOVIO 在 T 細胞治療前後的應用越來越廣泛。

Taking our results for the first half of the year into account, including the atypical level of returns in the first quarter of this year, we expect net product revenue for full-year 2025 will be in the range of $110 million to $120 million. Finally, we continue to expand global patient access to selinexor and are now approved in various indications in 50 countries. This is translating into growth in royalty revenue from Menarini, Antengene and other international partners. Royalty revenue increased 28% to $1.6 million in the second quarter of 2025 compared to the second quarter of 2024, reflecting increased global demand for XPOVIO and NEXPOVIO.

考慮到我們上半年的業績，包括今年第一季非典型的回報水平，我們預計 2025 年全年淨產品收入將在 1.1 億美元至 1.2 億美元之間。最後，我們繼續擴大全球患者獲得 selinexor 的機會，目前該藥物已在 50 個國家獲得各種適應症的批准。這意味著來自美納里尼、安騰醫藥和其他國際合作夥伴的專利費收入將會成長。2025 年第二季的特許權使用費收入與 2024 年第二季相比成長 28%，達到 160 萬美元，反映出全球對 XPOVIO 和 NEXPOVIO 的需求增加。

With data from our Phase 3 SENTRY trial in sight, our commercial team is preparing for a very rapid launch in myelofibrosis, if approved. As outlined on slide 23, we continue to believe that our peak annual revenue opportunity in the US alone is up to approximately $1 billion, with additional royalty and milestone revenue globally.

隨著我們第三階段 SENTRY 試驗的數據即將公佈，如果獲得批准，我們的商業團隊正在為骨髓纖維化治療的快速推出做準備。正如第 23 張投影片所述，我們仍然相信，僅在美國，我們的年收入高峰機會就高達約 10 億美元，並且在全球範圍內還有額外的特許權使用費和里程碑收入。

As you think about this opportunity, keep in mind that the average real-world duration for the current standard of care is approximately 13 months. And given the data we have reported to date, we believe we may have an opportunity to extend this further when ruxolitinib is combined with selinexor.

當您考慮這個機會時，請記住目前護理標準的平均實際持續時間約為 13 個月。鑑於我們迄今為止報告的數據，我們相信當魯索利替尼與塞利尼索結合時，我們可能有機會進一步擴展這一範圍。

On slide 24, we outline why we believe we are well positioned for a rapid launch in myelofibrosis pending positive data and approval. As we've shared previously, 75% of the physicians that we surveyed say that they intend to adopt a combination therapy in myelofibrosis if one becomes available.

在第 24 張投影片上，我們概述了為什麼我們相信，在獲得積極數據和批准後，我們已做好準備，可以快速推出骨髓纖維化治療產品。正如我們之前所分享的，75% 接受我們調查的醫生表示，如果有聯合療法可用於治療骨髓纖維化，他們打算採用該療法。

If selinexor is approved in combination with ruxolitinib, we could be the first combination therapy on the market. We would be an all-oral therapy, which makes adoption much easier, especially in the community setting. On this point, there is an 80% overlap in the community between myelofibrosis and multiple myeloma prescribers that our organization is already calling on, which enables us to drive a rapid launch and minimizes the upfront investment required for the launch.

如果 selinexor 與 ruxolitinib 聯合用藥獲得批准，我們可能會成為市場上首個聯合療法。我們將採用全口服療法，這使得採用變得更加容易，特別是在社區環境中。在這一點上，我們組織已經在呼籲的骨髓纖維化和多發性骨髓瘤處方者在社區中有 80% 的重疊，這使我們能夠推動快速啟動，並最大限度地減少啟動所需的前期投資。

Finally, in endometrial cancer, as shown on slide 25, we continue to believe that we have a significant opportunity in the p53 wild-type and pMMR patient population, which represents approximately 50% of advanced or recurrent endometrial cancer patients. Similar to what I outlined from myelofibrosis, there is a large overlap between the potential community-based oncologists caring for endometrial cancer patients and those we are already engaging with.

最後，對於子宮內膜癌，如第 25 張幻燈片所示，我們仍然相信，在 p53 野生型和 pMMR 患者群體中，我們擁有重大機會，該群體約佔晚期或復發性子宮內膜癌患者的 50%。與我從骨髓纖維化中概述的情況類似，照顧子宮內膜癌患者的潛在社區腫瘤學家與我們已經接觸的腫瘤學家之間存在很大的重疊。

Now, I'll turn the call over to Lori.

現在，我將把電話轉給 Lori。

Good morning, everyone, and thank you, Sohanya. Turning to our financials. Since we issued a press release earlier today with the full financial results, I will focus on the highlights and reviewing our guidance for 2025 on slide 27.

大家早安，謝謝你，Sohanya。談到我們的財務狀況。由於我們今天早些時候發布了一份包含完整財務業績的新聞稿，因此我將在第 27 張幻燈片上重點介紹其中的亮點並回顧我們對 2025 年的指導。

Total revenue for the second quarter of 2025 was $37.9 million compared to $42.8 million for the second quarter of 2024. The decline was primarily attributable to $6 million of non-recurring license related revenue from our partners recognized during the second quarter of 2024. US XPOVIO net product revenue for the second quarter of 2025 was $29.7 million compared to $28 million for the second quarter of 2024.

2025 年第二季總營收為 3,790 萬美元，而 2024 年第二季總營收為 4,280 萬美元。下降主要歸因於我們 2024 年第二季確認的來自合作夥伴的 600 萬美元非經常性許可相關收入。美國 XPOVIO 2025 年第二季淨產品收入為 2,970 萬美元，而 2024 年第二季為 2,800 萬美元。

As expected, the rate of product returns this quarter reverted to historic levels following the atypical increase reported in the first quarter of this year. As a result, the gross to net provisions for XPOVIO in the second quarter were 26.8%, down from the 45% that we reported in the first quarter of this year and down from 29.3% in the second quarter of 2024.

正如預期的那樣，在今年第一季出現非典型增長之後，本季的產品退貨率已恢復到歷史水平。因此，XPOVIO 第二季的總撥備與淨撥備比率為 26.8%，低於我們今年第一季報告的 45%，也低於 2024 年第二季的 29.3%。

The year-over-year decline was primarily driven by mix and lower 340B discounts in the second quarter of 2025. We expect our gross to net provisions will remain relatively consistent with Q2 2025 for the remainder of the year.

年比下降主要是由於 2025 年第二季的產品組合和 340B 折扣較低所致。我們預計，在今年剩餘時間內，我們的總撥備與淨撥備比率將與 2025 年第二季保持相對一致。

R&D expenses for the second quarter of 2025 were $32.8 million, down 15% when compared to $38.4 million for the second quarter of 2024. The decrease was due to a reduction in head count and contractors related to our cost optimization initiatives, combined with lower clinical trial and related costs, primarily from our Phase 3 clinical trial in multiple myeloma.

2025 年第二季的研發費用為 3,280 萬美元，與 2024 年第二季的 3,840 萬美元相比下降了 15%。減少的原因是與我們的成本優化計劃相關的員工數量和承包商的減少，加上臨床試驗和相關成本的降低，主要是來自我們針對多發性骨髓瘤的 3 期臨床試驗。

SG&A expenses for the second quarter of 2025 were $28.5 million, down 8% when compared to $31.1 million for the second quarter of 2024. The decrease was primarily due to the realization of previously implemented cost reduction initiatives.

2025 年第二季的銷售、一般及行政費用為 2,850 萬美元，與 2024 年第二季的 3,110 萬美元相比下降 8%。下降的主要原因是先前實施的成本削減措施的實現。

Interest expense was $11.2 million in the second quarter of 2025, up from $8.9 million in the second quarter of 2024. As a reminder, we announced a refinancing in the second quarter of 2024 that raised interest expense. However, there was only a partial quarter impact in the second quarter of 2024. Last year's refinancing also resulted in a $44.7 million gain on the extinguishment of debt in the second quarter of 2024.

2025 年第二季的利息支出為 1,120 萬美元，高於 2024 年第二季的 890 萬美元。提醒一下，我們在 2024 年第二季宣布了再融資，這增加了利息支出。不過，2024 年第二季僅產生了部分季度影響。去年的再融資也導致 2024 年第二季債務清償收益為 4,470 萬美元。

Other expense was $2.2 million in the second quarter of 2025 compared to $14.3 million of other income in the second quarter of 2024. These amounts were attributable to reoccurring non-cash fair value remeasurements of embedded derivatives and liability classified common stock warrants related to the refinancing transactions in the second quarter of 2024.

2025 年第二季的其他支出為 220 萬美元，而 2024 年第二季的其他收入為 1,430 萬美元。這些金額歸因於 2024 年第二季與再融資交易相關的嵌入式衍生性商品和負債分類普通股認股權證的重複非現金公允價值重計量。

We reported a net loss of $37.3 million or $4.32 per share on a GAAP basis. This figure includes $11.2 million in interest expense related to our debt instruments, as well as approximately $2 million in noncash losses from the remeasurement of embedded derivatives and liability classified common stock warrants.

根據 GAAP 計算，我們的淨虧損為 3,730 萬美元，即每股 4.32 美元。這一數字包括與我們的債務工具相關的 1,120 萬美元利息費用，以及因重新計量嵌入式衍生性商品和負債分類普通股認股權證而產生的約 200 萬美元非現金損失。

Our net loss from operations was $24.5 million for the second quarter of 2025. This operating result reflects the performance of our core business during the quarter. From an earnings per share perspective, our GAAP EPS includes both interest expense and mark-to-market impact of the warrant and derivative remeasurement.

2025 年第二季度，我們的營業淨虧損為 2,450 萬美元。這項經營業績反映了我們本季核心業務的表現。從每股盈餘的角度來看，我們的 GAAP EPS 包括利息費用以及認股權證和衍生性商品重估的市價影響。

We continue to be very diligent in allocating our resources and pipeline prioritization. We announced a roughly 20% reduction in our workforce in early July. You will start to see the financial impact of these actions when we report our results for the fourth quarter of this year.

我們繼續非常勤勉地分配我們的資源和管道優先順序。我們在 7 月初宣布裁員約 20%。當我們報告今年第四季的業績時，您將開始看到這些行動的財務影響。

In 2026, we expect these actions to lower our annual spend by approximately $13 million. We exited the second quarter of 2025 with cash, cash equivalents, restricted cash and investments of $52 million compared to $109.1 million as of December 31, 2024.

到 2026 年，我們預計這些措施將使我們的年度支出降低約 1,300 萬美元。截至 2025 年第二季度，我們的現金、現金等價物、受限現金和投資為 5,200 萬美元，而截至 2024 年 12 月 31 日為 1.091 億美元。

Based on our current operating plans, our guidance for the full year of 2025 is as follows: total revenue of $140 million to $155 million, consisting of US XPOVIO net product revenue and license, royalty, and milestone revenue expected to be earned from our partners, primarily Menarini and Antengene. US XPOVIO net product revenue to be in the range of $110 million to $120 million.

根據我們目前的營運計劃，我們對 2025 年全年的預期如下：總收入 1.4 億美元至 1.55 億美元，包括美國 XPOVIO 淨產品收入以及預計從我們的合作夥伴（主要是 Menarini 和 Antengene）獲得的許可、特許權使用費和里程碑收入。美國 XPOVIO 淨產品收入將介於 1.1 億美元至 1.2 億美元之間。

R&D and SG&A expenses to be in the range of $240 million to $250 million. And finally, we expect our existing liquidity, including the revenue we expect to generate from XPOVIO net product sales, as well as revenue generated from our license agreements, will be sufficient to fund our planned operations to the October 15 maturity of our senior convertible notes.

研發和銷售、一般及行政費用在 2.4 億美元至 2.5 億美元之間。最後，我們預計我們現有的流動資金（包括我們預計從 XPOVIO 淨產品銷售中產生的收入以及從我們的許可協議中產生的收入）將足以資助我們計劃的運營，直到我們的高級可轉換票據於 10 月 15 日到期。

Excluding the remaining $24.5 million 2025 notes maturity, and $25 million minimum liquidity covenant, we expect that our liquidity is sufficient to fund our planned operations into January 2026. As we address this, we are working closely with our advisers, including Centerview Partners, to explore potential financing and strategic alternatives to enhance liquidity and maximize value.

除去剩餘的 2450 萬美元 2025 年到期票據和 2500 萬美元最低流動性契約，我們預計我們的流動性足以資助我們到 2026 年 1 月的計劃運營。在解決這個問題時，我們正在與包括 Centerview Partners 在內的顧問密切合作，探索潛在的融資和策略替代方案，以提高流動性並實現價值最大化。

I will now turn the call back to Richard for some final thoughts.

現在我將把電話轉回給理查德，請他發表一些最後的看法。

Thank you, Lori. Turning to slide 29. We continue to believe that myelofibrosis in endometrial cancer, depending on the data from our ongoing Phase 3 clinical trials, are both game-changing opportunities for patients and our organization. With the myelofibrosis opportunity alone, representing up to a potential $1 billion in peak annual revenue in the US alone.

謝謝你，洛瑞。翻到第 29 張投影片。我們仍然相信，根據我們正在進行的 3 期臨床試驗的數據，子宮內膜癌中的骨髓纖維化對於患者和我們的組織來說都是改變遊戲規則的機會。僅就骨髓纖維化治療機會而言，僅在美國就可能帶來高達 10 億美元的年收入高峰。

To deliver on these opportunities, we are working with urgency and discipline to address our liquidity, while keeping our focus squarely on the opportunity in front of us to bring meaningful, much needed innovation to patients and generate significant value.

為了抓住這些機會，我們正在緊急而有紀律地解決我們的流動性問題，同時將我們的注意力集中在我們面前的機會上，為患者帶來有意義的、急需的創新並創造巨大的價值。

I'd like to thank our employees, our partners and our investors for their continued support and belief in our potential. We look forward to updating you on our progress in the coming months. And I would now like to ask the operator to open the call up to the Q&A portion of today's call. Operator?

我要感謝我們的員工、合作夥伴和投資者對我們潛力的持續支持和信任。我們期待在未來幾個月向您通報我們的進展。現在我想請接線生開始今天電話會議的問答部分。操作員？

(Operator Instructions) Ted Tenthoff, Piper Sandler.

（操作員指示）Ted Tenthoff，Piper Sandler。

I guess one biggest question has to do -- really two, if I may. First, just on myelofibrosis, everything seems to be pointing in the right direction. What's your biggest worry about that potential readout? Is it Jakafi doing better? Is there -- what could be the snake hiding in the bushes or the graphs or whatever that could surprise us?

我想最大的問題有一個——實際上兩個，如果可以的話。首先，就骨髓纖維化而言，一切似乎都指向正確的方向。對於這個潛在的讀數，您最大的擔憂是什麼？Jakafi 表現比較好嗎？有沒有──隱藏在灌木叢或圖表中的蛇會是什麼，或是其他什麼會讓我們感到驚訝的東西？

And then the second question is just with, really, three big readouts next year with myelofibrosis, the XPORT-MM-031 trial and also endometrial. How are you planning on prepping and being ready for all of those data readouts at the same time? Is that going to cause any problems just in terms of processing everything?

第二個問題是，明年實際上有三個重要的讀數，分別是骨髓纖維化、XPORT-MM-031 試驗和子宮內膜。您計劃如何同時準備並準備好讀取所有這些資料？就處理所有事情而言，這會造成任何問題嗎？

Yes. Thanks, Ted. A couple of great questions. I'll take the second one first, and that's a great opportunity that we're excited about, to have three big readouts in front of us and to be getting ready for potentially positive data across all those readouts, is what we're super excited about as an organization. Obviously, building on the foundation in multiple myeloma, I think that's something which is our bread and butter organization is really ready for.

是的。謝謝，泰德。有幾個很好的問題。我首先選擇第二個，這是一個很好的機會，我們對此感到興奮，我們面前有三個重要的讀數，並為所有這些讀數中可能出現的積極數據做好準備，這是我們作為一個組織感到非常興奮的事情。顯然，在多發性骨髓瘤的基礎上，我認為這是我們的支柱組織真正準備好的事情。

Myelofibrosis is a key area for us, obviously, and you've heard us talk -- and we talked again today that there is significant overlap in the prescriber base. So to be able to build on our foundation, leverage our commercial capabilities, and get out and start being able to get ready for myelofibrosis and ultimately launching it, pending positive data, again, I think we're well ready for.

顯然，骨髓纖維化是我們的一個重點領域，您已經聽到我們談論過——我們今天再次談到，處方者基礎存在很大的重疊。因此，為了能夠鞏固我們的基礎，利用我們的商業能力，並開始為骨髓纖維化做好準備，並最終啟動它，等待積極的數據，我認為我們已經做好了充分的準備。

And then, endometrial cancer, largely the same. There's a lot of overlap because a number of these patients, both in myelofibrosis and endometrial cancer are seen in the community. So our organization, our payer capabilities, our medical affairs capabilities, our commercial capabilities, all have a lot of synergy to be able to bring both myelofibrosis and endometrial cancer to patients rapidly.

然後，子宮內膜癌也大致相同。存在著許多重疊，因為社區中有許多患有骨髓纖維化和子宮內膜癌的患者。因此，我們的組織、付款人能力、醫療事務能力、商業能力都具有很大的協同作用，能夠迅速為患者帶來骨髓纖維化和子宮內膜癌。

So that's a good problem that we're excited about. And the organization already, is starting to work on getting ready for myelofibrosis, obviously, is our next potentially transformative opportunity and we're looking forward to updating you more on the future.

所以這是一個令我們興奮的好問題。組織已經開始為骨髓纖維化做好準備，顯然，這是我們下一個潛在的變革機會，我們期待向您提供更多關於未來的資訊。

And for the second part of the question, I'll turn that over to Reshma to talk with you about MF. Our -- and talk about our biggest worry, I think there's just -- broadly, I'll say, it's just a high level of excitement, really a high level of excitement that we're building on the foundation that's been put in place with ruxolitinib. And so to be able to potentially combine with the standard of care, and create a new standard of care for patients, obviously, is very exciting for us, especially given that that's an all-oral with two already approved medications.

對於問題的第二部分，我將交給 Reshma 來和您討論 MF。說到我們最大的擔憂，我認為——總的來說，我會說，這只是一種高度的興奮，我們在蘆可替尼的基礎上真正建立了一種高度的興奮。因此，能夠潛在地與標準護理相結合，並為患者創造新的護理標準，顯然對我們來說非常令人興奮，特別是考慮到這是一種已經獲得兩種批准的全口服藥物。

But I'll let Reshma maybe share with you what her biggest worry is with regards to looking at the Phase 3 readout with selinexor and ruxolitinib.

但我會讓 Reshma 與您分享她在查看 selinexor 和 ruxolitinib 的 3 期讀數時最大的擔憂是什麼。

Yes. Thanks, Richard, and thanks, Ted, for the question. It's interesting. Worry, I'm not sure I would couch it in those words. As Richard was mentioning, right, we've been exploring myelofibrosis for so many years.

是的。謝謝理查德，也謝謝泰德提出這個問題。這很有趣。擔心，我不確定我是否會用這些話來表達。正如理查德所提到的，我們對骨髓纖維化的研究已經很多年了。

I mean, seven-plus years, both with preclinical data, obviously, teasing apart the mechanism. We've got multiple clinical data sets. We've got a Phase 1 study evaluating the combination in this relevant patient population of JAK-naive myelofibrosis.

我的意思是，七年多的時間，顯然都有臨床前數據，可以梳理出其中的機制。我們有多個臨床數據集。我們已進行一項 I 期研究，評估該組合療法在 JAK 初治骨髓纖維化相關患者群體中的作用。

And I have to say, I like what we've got, right? We've shown some very, very compelling SVR data, SVR35 at week 24 that more than doubles what we've observed with historical ruxolitinib that leads to SVR rates and only approximately one-third of all patients even with symptom improvement. And I'll admit, right, symptom improvement has been the Achilles heel of so many Phase 3 trials.

我必須說，我喜歡我們所擁有的，對吧？我們已經展示了一些非常非常令人信服的 SVR 數據，第 24 週的 SVR35 是我們觀察到的歷史蘆可替尼的兩倍多，導致 SVR 率，並且只有大約三分之一的患者症狀得到改善。我承認，症狀改善一直是許多 3 期試驗的致命弱點。

With that said, I like the data that we've observed to date, both from a TSS50 standpoint, but also an absolute TSS, that latter, which shows an 18.5 point improvement at week 24 relative to baseline. And again, I always contextualize that with some of the monotherapy data that also shows some very compelling TSS data as well.

話雖如此，我喜歡我們迄今為止觀察到的數據，無論是從 TSS50 的角度，還是從絕對 TSS 的角度，後者顯示第 24 週相對於基線提高了 18.5 點。再次強調，我總是將其與一些單一療法數據聯繫起來，這些數據也顯示了一些非常令人信服的 TSS 數據。

But beyond that, right, SVR and TSS are only two of the key hallmarks that we evaluate in myelofibrosis. I really am quite encouraged by the disease modification data, both with the cytokines as well as bone marrow fibrosis, obviously, the impact on hemoglobin stabilization. This really intriguing observation that we're also including improving the safety, especially the Grade 3-plus anemia rates relative to historical control.

但除此之外，SVR 和 TSS 只是我們評估骨髓纖維化的兩個關鍵指標。我確實對疾病改良數據感到非常鼓舞，包括細胞激素和骨髓纖維化，顯然還有對血紅素穩定的影響。這是一個非常有趣的觀察結果，我們還包括提高安全性，特別是相對於歷史控制的 3 級以上貧血率。

So I think like when I step back, right, I mean, the Phase 3 is going to be the Phase 3. But I think going into that Phase 3, I really, again, like what we see in that, the combination really can meaningfully improve on not only the key endpoints of SVR35 and absolute TSS, but all of the areas that obviously are very relevant to the patient as well as their physician.

所以我想當我退後一步時，對的，我的意思是，第三階段將是第三階段。但我認為進入第 3 階段後，我真的再次喜歡我們所看到的結果，這種組合確實不僅可以顯著改善 SVR35 和絕對 TSS 的關鍵終點，而且可以顯著改善所有與患者及其醫生非常相關的領域。

That's very helpful. And I share your enthusiasm. So I'm looking forward to the data readouts.

這非常有幫助。我和你一樣充滿熱情。所以我期待數據讀數。

Colleen Kusy, Baird.

科琳·庫西，貝爾德。

Helpful update on the baseline characteristics for the pivotal MF combo study. You spoke to higher TSS at baseline. Can you talk about that a little bit more on how you think that will impact your results and specifically, have you seen a ceiling effect with other trials?

對關鍵 MF 組合研究的基線特徵進行有益的更新。您在基線時談到了更高的 TSS。您能否進一步談談這將如何影響您的結果，特別是，您是否在其他試驗中看到天花板效應？

Yes. Thanks, Colleen. Great question. So some of the data, especially when we look at historical trials in this JAK-naive myelofibrosis, it does just whether you're looking at TSS50 or absolute TSS that the higher the baseline, right, the more likely you're going to see that meaningful outcome, either a 50% improvement or that proportion of patients who can achieve that 50% improvement. Or overall, that average reduction in that mean TSS at week 24 relative to baseline.

是的。謝謝，科琳。好問題。因此，一些數據，特別是當我們查看這種 JAK 初治骨髓纖維化的歷史試驗時，無論您查看的是 TSS50 還是絕對 TSS，基線越高，就越有可能看到有意義的結果，無論是 50% 的改善還是能夠實現 50% 改善的患者比例。或者總體而言，第 24 週的平均 TSS 相對於基線的平均減少量。

So the higher you can push it, the more likely again, you can achieve a meaningful outcome. And so again, these are just preliminary characteristics. We have not enrolled all of our patients. So ultimately, when we complete enrollment, we'll take a snapshot of where that baseline TSS is.

因此，你推動的越高，你就越有可能再次取得有意義的成果。所以，這些只是初步特徵。我們尚未招募所有患者。因此，最終，當我們完成註冊時，我們將對基線 TSS 的位置進行快照。

But I'm really encouraged where that -- where the evolution has been within the Phase 3 trial, i.e., again, pushing to higher baseline TSS. So yes, excited to see where we are right now.

但我真的很受鼓舞，因為第三階段試驗的進展已經取得進展，即再次推動更高的基線 TSS。是的，我很高興看到我們現在所處的位置。

Okay. And one quick follow-up, if I can. You touched on this a little bit, but can you just further explain the rationale again for why you think you're seeing the lower rates of Grade 3/4 anemia with the combination? And how important do you think that will be for physicians and potential uptake of the combination?

好的。如果可以的話，我再快速跟進。您稍微提到了這一點，但是您能否進一步解釋為什麼您認為這種組合會導致 3/4 級貧血發生率較低？您認為這對於醫生和潛在的組合採用有多重要？

Yes. It's a really, really intriguing observation. And I really do think that it's probably due to the disease modification that is occurring with selinexor plus ruxolitinib. We've touched upon some really compelling cytokine data. This was back at EHA, in June, when we looked at selinexor as a monotherapy in that previously treated population.

是的。這是一個非常非常有趣的觀察。我確實認為這可能是由於 selinexor 和 ruxolitinib 聯合治療後病情發生了變化。我們已經觸及了一些真正令人信服的細胞激素數據。這是 6 月在 EHA 舉行的活動，當時我們將 Selinexor 作為單一療法應用於先前接受過治療的人。

What those data suggested is that it's decreasing key cytokines that are involved in all aspects of anemia, specifically, hepcidin, ferritin, et cetera, right? You see decreases in those rates. Obviously or potentially could be translating to lower grade 3-plus anemia.

這些數據表明，它正在減少與貧血各個方面有關的關鍵細胞因子，特別是鐵調素、鐵蛋白等，對嗎？您會看到這些比率有所下降。顯然或潛在地可能轉化為低度 3 級以上貧血。

I'm really liking with what we see from the very preliminary data coming out of the bone marrow fibrosis, too, a really marked decrease in that reticulin density. It suggests that you're clearing out that marrow. And potentially allowing for some repopulation of those key cells that ultimately can produce erythrocytes and lead to higher hemoglobin.

我真的很喜歡我們從骨髓纖維化的初步數據中看到的結果，網狀蛋白密度確實明顯下降。這表示你正在清理骨髓。並可能允許一些關鍵細胞重新繁殖，最終產生紅血球並導致更高的血紅蛋白。

So that also could not only lead to efficacy, i.e., higher hemoglobin, but also potentially translate to lower grade 3-plus rates. Early days, right? These are just hypothesis-generating data. But I love the fact that we see these clinical outcomes married with these disease modification data that, again, can explain both the efficacy and safety aspects that we see in our trials.

因此，這不僅可以提高療效，即提高血紅素，還可能降低 3 級以上發病率。還只是早期吧？這些只是假設生成的數據。但我很高興看到這些臨床結果與這些疾病改良數據結合在一起，這再次解釋了我們在試驗中看到的功效和安全性方面。

Peter Lawson, Barclays.

巴克萊銀行的彼得·勞森。

And just as we think about revenues and the drivers, what was the contribution? I may have missed this volume pricing versus inventory? And then how should we think about that for the rest of the year? And then I have a follow-up.

當我們考慮收入和驅動因素時，貢獻是什麼？我可能錯過了批量定價與庫存的關係？那麼，我們該如何考慮今年剩下的時間呢？然後我有一個後續問題。

Yes. Thanks, Peter. Inventory was relatively consistent across the period. So I think as Sohanya shared, there's a balance, we saw an improvement in the GTN. And that's something that we obviously talked to last quarter when we had this onetime returns issue. And so overall, we also have seen demand to be relatively consistent. So that's the balance in the drivers.

是的。謝謝，彼得。整個期間的庫存相對穩定。因此我認為，正如 Sohanya 所說，存在著一種平衡，我們看到了 GTN 的改進。上個季度，當我們遇到一次性退貨問題時，我們顯然已經討論過這個問題。因此整體而言，我們也看到需求相對穩定。這就是驅動程式的平衡。

Great. And then that early blinded safety data looks really encouraging for lower grade 3 anemia and discontinuation rates versus ruxolitinib. How confident are you that those kind of backing out of data sets will hold once it's unblinded?

偉大的。然後，早期的盲法安全數據看起來確實令人鼓舞，因為與蘆可替尼相比，3 級貧血和停藥率較低。一旦揭開盲目性，您對這些資料集的支援有多大信心？

It's a good question. And Peter, I always say, I wish I had that perfect crystal ball. Sometimes crystal balls can be fuzzy. But with that said, I like the evolution that we've seen in these blinded safety data. We've taken a couple of snapshots.

這是個好問題。彼得，我總是說，我希望我有一個完美的水晶球。有時水晶球可能會變得模糊。但話雖如此，我喜歡我們在這些盲法安全資料中看到的進展。我們拍攝了幾張快照。

So we've taken advantage of these 61 patients. They, again, were included as part of that futility analysis that the Data Safety Monitoring Board evaluated earlier this year. With approximately six months of follow-up, we see a really nice evolution in that safety profile, especially when we extrapolate with historical ruxolitinib.

所以我們利用了這 61 位患者。它們再次被納入資料安全監測委員會今年稍早評估的無效性分析的一部分。經過大約六個月的跟踪，我們看到了安全性方面的真正良好的進展，特別是當我們根據歷史上的蘆可替尼進行推斷時。

And when we continue to follow those patients and took an updated snapshot, as of July 1, we really see a similar kind of trend. Yes, numerically, we do see increases in some of these rates of AEs, whether it's all grade or grade 3-plus, but a really nice compared to historical ruxolitinib.

當我們繼續追蹤這些患者並拍攝最新快照時，截至 7 月 1 日，我們確實看到了類似的趨勢。是的，從數字上看，我們確實看到一些 AE 發生率有所增加，無論是所有級別還是 3 級以上，但與歷史上的蘆可替尼相比，這確實很不錯。

I think one of the key things, when I do these extrapolations or I should say, we, as a team, do these extrapolations, is that historical ruxolitinib safety data has been relatively consistent, right? So when we look at the MANIFEST Phase 3 trial versus the COMFORT right? They span more than a decade.

我認為，當我進行這些推斷時，或者我應該說，我們作為一個團隊進行這些推斷時，關鍵的事情之一是，歷史上的蘆可替尼安全數據是相對一致的，對嗎？那麼，當我們對比 MANIFEST 第 3 階段試驗和 COMFORT 時，情況如何？它們跨越了十多年。

And yet, again, it's interesting to see that that ruxolitinib safety data, by and large, is very consistent. So it allows us or it gives us a little bit more confidence when we extrapolate to what the combination is likely going to see as relatively stable. So ultimately, we'll need to just see what the Phase 3 data demonstrate. But again, encouraged by this preliminary observation.

然而，再次有趣的是，蘆可替尼的安全數據總體上非常一致。因此，當我們推斷組合可能相對穩定時，它讓我們更有信心。所以最終，我們只需要看看第三階段的數據能證明什麼。但再次，這項初步觀察令我們感到鼓舞。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特（Maury Raycroft），傑富瑞集團（Jefferies）。

This is Amy on for Maury. Congrats on the quarter. I have two questions, one on the endometrial, the other on the SENTRY-2 study. So for the endometrial Phase 3, can you talk about the enrollment progress so far? And what percentage of the target has already been enrolled?

這是 Amy 為 Maury 表演的。恭喜本季取得佳績。我有兩個問題，一個關於子宮內膜，另一個關於 SENTRY-2 研究。那麼對於子宮內膜 3 期研究，您能談談目前的入組進展嗎？目標族群中已經招募了多少比例的人？

And for the SENTRY-2, could you help us understand how the protocol amendment would help with enrollment of the study, considering the Phase 3 SENTRY and this original SENTRY-2 are not in the same population?

對於 SENTRY-2，考慮到第 3 階段 SENTRY 和原始的 SENTRY-2 不屬於同一人群，您能否幫助我們了解協議修正案將如何幫助研究的招募？

And what is the bar for success now for this amended study? And would you plan to show in the top line? And how should we contextualize the data with the new population?

那麼，這項修訂研究的成功標準是什麼？您打算出現在頂級節目中嗎？我們該如何將數據與新人連結起來？

Yes. Thanks, Amy. So I'll take the first one. For endometrial cancer, so enrollment is very steady, right? This is a unique study in that it's a biomarker-driven maintenance study.

是的。謝謝，艾米。所以我會選第一個。對於子宮內膜癌來說，入學率非常穩定，對嗎？這是一項獨特的研究，因為它是一項由生物標記驅動的維護研究。

What we are seeing right now and aiming to complete is that what we call the top of the funnel, i.e., the number of patients who have submitted samples to Foundation Medicine for assessment of their p53 status. We see nice flows of samples into that bucket and anticipate top line results in the middle of 2026. So again, very encouraged by the progress made to date.

我們現在看到的以及我們想要完成的目標是所謂的漏斗頂部，即向 Foundation Medicine 提交樣本以評估其 p53 狀態的患者數量。我們看到大量樣本流入該桶，並預計在 2026 年中期獲得頂線結果。因此，我對迄今為止的進展感到非常鼓舞。

We have not released any target enrollment as of today. So we're not giving out any numbers again. We're confident with what we are seeing at the top of the funnel, as well as the subsequent randomization that we are going to hit top line results in the middle of 2026.

截至今天我們尚未公佈任何目標招生人數。所以我們不會再透露任何數字。我們對漏斗頂部所看到的情況以及隨後的隨機化充滿信心，我們將在 2026 年中期取得頂線成果。

In terms of SENTRY-2, so another good question. So let me just back up for a minute. So SENTRY-2 was also looking at that JAK-naive myelofibrosis patient population, we're evaluating selinexor as a monotherapy in a single-arm cohort in this population.

就 SENTRY-2 而言，這是另一個好問題。所以讓我先回顧一下。因此，SENTRY-2 也在研究未接受 JAK 治療的骨髓纖維化患者群體，我們正在評估 selinexor 作為該族群單一療法的效果。

Now, keep in mind that the population had been different and still is different than our combination trial SENTRY, the ongoing Phase 3, largely based upon their platelet counts. So SENTRY-2 is just enrolling patients who have baseline platelet counts between 50 and 100. SENTRY is enrolling patients with 100 and above.

現在，請記住，人群曾經不同，並且仍然與我們的聯合試驗 SENTRY（正在進行的第 3 階段）不同，這主要取決於他們的血小板計數。因此，SENTRY-2 僅招募基線血小板計數在 50 至 100 之間的患者。SENTRY 正在招募 100 歲以上的患者。

What we plan to do -- so this hasn't occurred yet, but what we plan to do is to amend the trial to allow all patients with baseline platelet counts of 50 all the way, there's no limit to enroll as part of this trial. So now that we are opening up that baseline platelet cap, we do anticipate that the enrollment is going to pick up relative to what we've seen to date.

我們計劃要做的是——這還沒有發生，但我們計劃要做的是修改試驗，允許所有基線血小板計數為 50 的患者無限制地參加本次試驗。因此，既然我們現在已經開放了基線血小板上限，我們確實預計入學人數將比我們迄今為止看到的情況增加。

In terms of the bar, so because the amendment has not been issued yet, we don't see any difference in the bar. So we do anticipate that the majority of the patients enrolled is part of the 60-milligram cohort are still going to be that moderate thrombocytopenia population, 50 to 100. This is a very high unmet need, small population at approximately 14%.

就標準而言，由於修正案尚未發布，因此我們看不出標準有任何差異。因此，我們確實預計，60 毫克組的大部分患者仍將是中度血小板減少症患者，人數為 50 至 100 人。這是一個非常高的未滿足需求，人口較少，約 14%。

Because there's not really effective therapies for that population, that bar is anywhere above 25%, right? 25% to 30% relative to historical controls of approximately 15%.

因為對該族群來說沒有真正有效的治療方法，所以這個門檻肯定在 25% 以上，對嗎？相對於歷史控制率約 15% 而言，這一數字上升至 25% 至 30%。

Brian Abrahams, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Brian Abrahams。

I guess maybe asking a safety question a little bit of a different way. I'm curious, like what's your view as to what the potential reasons why you're seeing this possible overall difference in tolerability when you look at those extrapolated safety rates versus the Phase 1? Is there anything you can tell us about the use of antiemetics in the study, whether patients are continuing to use them or stopping after those first 2 mandatory cycles?

我想也許可以用稍微不同的方式來問安全問題。我很好奇，當您查看與第一階段相比推斷出的安全率時，您認為導致耐受性出現這種總體差異的潛在原因是什麼？您能否告訴我們有關研究中止吐藥使用情況的任何信息，患者是否繼續使用它們，還是在前兩個強制週期後停止使用？

And then my second question is there's been some recent changes in FDA leadership at SEDAR. And I'm curious if you had any updated communications with the agency since your alignment on the new co-primary endpoints for the Phase 3? And your level of confidence that they're positioned on what's going to be required remains the same as your prior feedback?

我的第二個問題是，FDA 在 SEDAR 的領導層最近發生了一些變化。我很好奇，自從你們就第三階段新的共同主要終點達成一致以來，是否與該機構進行過任何更新的溝通？您對於他們所處位置的信心程度是否與您先前的回饋一樣？

Thanks, Brian, for the question. So it really is a very nice evolution, both to historical ruxolitinib, but as you mentioned, also to the Phase 1 data. And arguably, I think some of the greatest benefit is around the GI toxicity. It's very well known with selinexor.

謝謝 Brian 提出的問題。因此，這確實是一個非常好的進展，不僅對歷史上的蘆可替尼而言，而且正如您所提到的，對第一階段的數據也是如此。並且可以說，我認為最大的益處在於胃腸道毒性。其因 selinexor 而廣為人知。

But what we see in our Phase 3 extrapolated data is a really nice improvement both with that nausea as well as vomiting. So in that Phase 1, yes, we saw 80% of the patients experience any grade nausea, approximately 50% of the patients experiencing any grade vomiting.

但我們在第 3 階段推斷的數據中看到，噁心和嘔吐都有了很好的改善。因此，在第一階段，是的，我們看到 80% 的患者出現不同程度的噁心，大約 50% 的患者有不同程度的嘔吐。

And what we are now, potentially, seeing in our Phase 3 is reduction in both the nausea and vomiting from 80% to 64%, even vomiting from 50% to now close to what you see and expect with historical ruxolitinib around 10%, 12%. I think you hit the hammer on the head, why do we see this? I think it's really because of all of the antiemetics.

我們現在可能在第 3 階段看到的是噁心和嘔吐減少，從 80% 減少到 64%，嘔吐甚至從 50% 減少到現在接近您看到和預期的歷史蘆可替尼的 10%、12% 左右的水平。我認為你擊中了要害，我們為什麼會看到這種情況？我認為這確實是因為所有的止吐藥。

So in our Phase 1 antiemetic usage was not consistent. So there was many patients, unfortunately, who did not take dual antiemetics. There were quite a few patients who only took one. They were some patients who didn't take any.

因此，我們在第一階段的止吐藥使用情況並不一致。因此，不幸的是，有許多患者沒有服用雙重止吐藥。有不少病人只服用了一片。他們是一些沒有服用任何藥物的病人。

In our Phase 3, we've really tightened that requirement. Virtually all of those patients above 90% are taking those dual antiemetics for the first two cycles and then its optional thereafter. And I think it's because of those required dual antiemetics, we see this improvement in nausea, but I think the really nice improvement is again in that vomiting, about from 50% all the way down to 10%. So a really nice improvement, not only to the Phase 1, but again also relative to historical ruxolitinib.

在第三階段，我們確實加強了這個要求。幾乎所有超過 90% 的患者都在前兩個週期服用雙重止吐藥，之後則可選擇是否服用。我認為這是由於需要雙重止吐藥，我們看到噁心症狀有所改善，但我認為真正好的改善還是在嘔吐方面，大約從 50% 下降到 10%。因此，這確實是一個很大的進步，不僅對於第一階段而言，而且相對於歷史上的蘆可替尼也是如此。

In terms of the FDA, yes, so lots of evolution going on with the FDA, as we all know. With that said, no additional feedback. So we got that feedback back in the third quarter of 2024, around the endpoint change and have not gotten any additional feedback. Because everything is so documented, we feel confident in the position that the FDA will ultimately take on our Phase 3 when we meet with them, hopefully, next year.

就 FDA 而言，是的，眾所周知，FDA 正在發生許多變化。話雖如此，但沒有其他反饋。因此，我們在 2024 年第三季收到了有關端點變更的回饋，但沒有收到任何其他回饋。因為一切都有記錄在案，所以我們對 FDA 最終在我們與 FDA 會面時（希望是在明年）對我們的第 3 階段採取的立場充滿信心。

And Brian, I think -- and just to add to that. I think when we look at the agency, I think we feel we're really positive about the evolutions and how they're focused on accelerating access to meaningful cures, treatments, and diagnostics. And just a couple of months back, we participated in a really valuable CEO listening tour with the commissioner and really appreciate the interactions, I think in the evolution. So continuing to look forward to working positive with them to bring new medicines to patients.

我認為布萊恩 — — 只是補充一下。我認為，當我們審視該機構時，我們對這些進展以及他們如何專注於加速獲得有意義的治療、治療和診斷方法感到非常樂觀。就在幾個月前，我們與專員一起參加了一次非常有價值的 CEO 傾聽之旅，我非常欣賞這次互動，我認為這是一個進步。因此，我們繼續期待與他們積極合作，為患者帶來新的藥物。

Jonathan Chang, Leerink Partners.

Jonathan Chang，Leerink Partners。

Can you discuss the scenarios being explored to enhance liquidity and maximize value? What existing and/or potential XPOVIO opportunities are being considered in these scenarios?

您能否討論一下正在探索的增強流動性和最大化價值的方案？在這些場景中正在考慮哪些現有和/或潛在的 XPOVIO 機會？

Thanks, Jonathan. I mean, on that side, there's really nothing more to add on this point beyond what we've stated in our 8-K in July and what we shared today in the press release and in our 10-Q. As we've stated, we are exploring a full range of financing and strategic alternatives that are going to enable us to extend our cash runway or enhance liquidity and maximize value.

謝謝，喬納森。我的意思是，在這方面，除了我們在 7 月的 8-K 報告中所述以及我們今天在新聞稿和 10-Q 報告中分享的內容之外，真的沒有什麼可以補充的了。正如我們所說，我們正在探索全方位的融資和策略替代方案，這將使我們能夠延長現金流或增強流動性並實現價值最大化。

We have engaged Centerview Partners, which, as you know, is a real leader in this area to help us through this. And we don't intend to discuss or disclose any further developments unless and until our Board has approved a real specific action or otherwise determined that further disclosure is appropriate.

我們已聘請 Centerview Partners 來幫助我們解決這個問題，正如您所知，它是該領域的真正領導者。我們不打算討論或披露任何進一步的發展，除非我們的董事會批准了一項真正的具體行動或以其他方式確定進一步披露是適當的。

So that's where we are now and continuing to work on it, obviously, as we move forward. And obviously, with XPOVIO, it encompasses the totality of XPOVIO.

這就是我們現在所處的狀態，顯然我們會繼續努力，繼續前進。顯然，有了 XPOVIO，它就涵蓋了 XPOVIO 的全部。

And I'm showing no further questions at this time. I would like to turn it back to Richard Paulson for closing remarks.

我現在沒有其他問題了。我想請理查保爾森作最後發言。

Thanks, operator. I think as you heard today, our organization is very focused on delivering on the opportunities in front of us. As we've stated, we're working with real urgency and with discipline to address our liquidity and keeping our focus squarely on the opportunities we have in front of us, which is why we do what we do every day, and that's to bring meaningful much needed innovation to patients and to generate significant value. So once again, I'd like to thank our employees, our partners, our investors for their continued support and the belief in our potential and thank you for joining the call today.

謝謝，接線生。我想正如你們今天所聽到的，我們的組織非常注重抓住我們面前的機會。正如我們所說，我們正在緊急而有紀律地解決我們的流動性問題，並將我們的注意力集中在我們面前的機會上，這就是我們每天所做的事情的原因，那就是為患者帶來有意義的、急需的創新並創造巨大的價值。因此，我要再次感謝我們的員工、合作夥伴和投資者對我們潛力的持續支持和信任，也感謝大家今天的電話會議。

Thank you, presenters. And ladies and gentlemen, this concludes today's conference call. Thank you all for joining. You may now disconnect.

謝謝各位主持人。女士們、先生們，今天的電話會議到此結束。感謝大家的加入。您現在可以斷開連線。