Karyopharm Therapeutics Inc (KPTI) 2025 Q3 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 third quarter 2025 financial results conference call. (Operator Instructions) Please be advised that this call is being recorded at the company's request.

早安.我叫盧迪，今天我將擔任你們的會議接線生。在此，我謹代表 Karyopharm Therapeutics 公司，歡迎各位參加 2025 年第三季財務業績電話會議。（操作員指示）請注意，本次通話正在依照本公司要求進行錄音。

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

現在我將把電話交給投資者關係和企業傳播高級副總裁布倫丹·斯特朗。請繼續。

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

早安，感謝各位參加今天的電話會議，共同討論 Karyopharm 2025 年第三季財務業績和公司近期進展。今天早上我們發布了一份新聞稿，詳細介紹了我們 2025 年第三季的財務表現。這份新聞稿以及我們將在今天電話會議中提到的幻燈片演示文稿，都可以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 will provide an update on our results for the third quarter of 2025 and discuss recent clinical developments.

如投影片 2 所示，今天的電話會議，我將與 Richard、Reshma、Sohanya 和 Lori 一起，介紹我們 2025 年第三季的業績，並討論最近的臨床進展。

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.

在我們正式發言之前，我要提醒各位，我們今天發表的各種言論構成了1995年《私人證券訴訟改革法案》安全港條款所指的前瞻性陳述，如幻燈片3所述。由於各種重要因素的影響，實際結果可能與這些前瞻性聲明所指出的結果有重大差異，這些因素包括我們在最近向美國證券交易委員會提交的 10-Q 表格或 10-K 表格的「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. I'll now turn the call over to Richard. Please turn to slide 4.

任何前瞻性陳述僅代表我們截至今日的觀點。雖然我們將來可能會選擇更新這些前瞻性聲明，但我們明確聲明，即使我們的觀點發生變化，我們也沒有義務這樣做。因此，您不應將這些前瞻性陳述視為我們截至任何後續日期的觀點。現在我將把電話交給理查。請翻到第4張投影片。

Thank you, Brendan, and thank you all for joining us today for Karyopharm's Q3 2025 earnings call. As we turn to slide 5, I'm pleased to share that this has been a very productive quarter for Karyopharm, one defined by meaningful clinical progress and strengthened financial flexibility that together set the stage for our next chapter of growth.

謝謝 Brendan，也謝謝各位今天參加 Karyopharm 2025 年第三季財報電話會議。翻到第 5 張幻燈片，我很高興地告訴大家，對於 Karyopharm 來說，這是一個碩果累累的季度，其特點是臨床取得了實質性進展，財務靈活性也得到了加強，這為我們下一個增長篇章奠定了基礎。

In Q3, we completed enrollment in our Phase III SENTRY trial in frontline myelofibrosis, marking a pivotal moment for Karyopharm. SENTRY represents a significant opportunity to redefine the standard of care for patients with myelofibrosis through the combination of selinexor plus ruxolitinib as a potential all-oral treatment option. With top-line results expected in March, we believe this trial could establish a new paradigm for how myelofibrosis is treated and further validate the relevance of XPO1 inhibition in hematological malignancies.

第三季度，我們完成了針對第一線骨髓纖維化的 III 期 SENTRY 試驗的患者招募，這標誌著 Karyopharm 的關鍵時刻。SENTRY 代表著一個重大的機會，透過將 selinexor 與 ruxolitinib 結合，作為一種潛在的全口服治療方案，重新定義骨髓纖維化患者的治療標準。預計 3 月將公佈初步結果，我們相信這項試驗可能會為骨髓纖維化的治療建立新的範式，並進一步驗證 XPO1 抑制在血液惡性腫瘤中的相關性。

The power of XPO1 inhibition is multidimensional. It simultaneously targets multiple pathways that enable malignant cell growth and proliferation. Targeting these relevant pathways concurrently overcomes the limitations of targeted therapies, such as ruxolitinib, a JAK inhibitor that mostly delivers symptomatic benefits that many consider palliative. This unique and potentially foundational mechanism could establish XPO1 inhibition as a key mechanism in myelofibrosis with further potential across the broader MPN landscape.

XPO1抑制的作用是多方面的。它同時靶向多種促進惡性細胞生長和增殖的路徑。同時針對這些相關路徑可以克服標靶治療的局限性，例如 JAK 抑制劑魯索替尼，它主要提供症狀緩解，許多人認為這只是安寧療護。這種獨特且可能具有奠基意義的機制可以將 XPO1 抑制確立為骨髓纖維化的關鍵機制，並有可能在更廣泛的 MPN 領域發揮進一步作用。

In October, we made significant progress in strengthening our financial foundation. Through comprehensive refinancing and capital restructuring, we secured approximately $100 million of financial flexibility and additional capital, extending our cash runway into the second quarter of 2026.

10月份，我們在加強財務基礎方面取得了重大進展。透過全面的再融資和資本重組，我們獲得了約 1 億美元的財務彈性和額外資本，使我們的現金儲備維持到 2026 年第二季。

Turning to our financial performance. Our profitable multi myeloma commercial organization provides a solid foundation on which to build. In the third quarter, we delivered total revenue of $44 million, an increase of 13% year-over-year, and US net product revenue grew 8.5%, reaching $32 million. This growth reflects the continued strength of XPOVIO in multiple myeloma and the disciplined execution of our commercial and operational teams.

接下來談談我們的財務表現。我們獲利的多發性骨髓瘤商業組織為未來的發展奠定了堅實的基礎。第三季度，我們實現了總營收 4,400 萬美元，年增 13%；美國淨產品收入成長 8.5%，達到 3,200 萬美元。這一成長反映了 XPOVIO 在多發性骨髓瘤領域持續的強勁實力，以及我們商業和營運團隊的嚴謹執行。

Importantly, we delivered this level of growth while continuing to reduce expenses. As we look ahead, our recent financing enables us to continue with focus and conviction around three core priorities. First, advancing our late-stage clinical programs, SENTRY and EC-042, which we believe have the potential to be truly transformative for patients and the company. Second, driving continued growth across our XPOVIO franchise; and third, maintaining financial discipline as we execute on our strategy and position Karyopharm for sustained success.

重要的是，我們在持續降低成本的同時，也實現了這樣的成長水準。展望未來，我們近期的融資使我們能夠繼續專注於三個核心優先事項並堅定不移地推進這些事項。首先，我們將推進後期臨床計畫 SENTRY 和 EC-042，我們相信這兩個計畫有可能真正改變病人和公司。第二，推動 XPOVIO 品牌持續成長；第三，在執行策略的同時保持財務紀律，使 Karyopharm 能夠取得持續成功。

Taken together, these underscore the momentum and transformation underway at Karyopharm. We are executing with clarity and purpose as we advance our mission to pioneer innovative cancer therapies that can meaningfully improve the lives of patients and deliver long-term value for all our stakeholders. As our next major milestone is the top-line myelofibrosis data from SENTRY, we will focus much of today's discussion on the science supporting this program and the significant commercial opportunity ahead. Now I'd like to turn the call over to Reshma to review our science.

總而言之，這些都突顯了 Karyopharm 正在發生的巨大發展勢頭和變革。我們正以清晰的目標和明確的方向推進我們的使命，即開創創新的癌症療法，從而切實改善患者的生活，並為所有利益相關者帶來長期價值。由於我們的下一個重大里程碑是 SENTRY 的骨髓纖維化主要數據，我們今天將重點討論支持該計畫的科學原理以及未來巨大的商業機會。現在我想把電話交給雷什瑪，讓她來回顧我們的科學觀點。

Thank you, Richard. There is a substantial need to develop new treatment options for patients with myelofibrosis. As shown on slide 7, this disease is heterogeneous and is defined by four hallmarks or defining features. These hallmarks include an enlarged spleen, abnormal blood cell production, bone marrow fibrosis, and constitutional symptoms. Furthermore, the median overall survival for intermediate to high-risk myelofibrosis patients is only four to five years.

謝謝你，理查。迫切需要為骨髓纖維化患者開發新的治療方案。如投影片 7 所示，這種疾病具有異質性，並由四個標誌性特徵或定義特徵所定義。這些特徵包括脾臟腫大、血球生成異常、骨髓纖維化和全身症狀。此外，中高危險群骨髓纖維化患者的中位總存活期僅四至五年。

Lastly, JAK inhibitors are the only approved therapy for myelofibrosis. And while they may decrease symptom burden and lead to very modest spleen reduction, relevant JAK inhibitors, including ruxolitinib, the standard of care in frontline myelofibrosis, do not target all of the relevant pathways implicated in myelofibrosis, including NF-kappa beta, p53, and fibrosis-inducing pathways. As a result, treatment of frontline myelofibrosis patients with monotherapy JAK inhibitors do not adequately address the relevant drivers of pathogenesis in myelofibrosis.

最後，JAK抑制劑是目前唯一獲準用於治療骨髓纖維化的療法。雖然它們可以減輕症狀負擔並導致脾臟輕微縮小，但相關的 JAK 抑制劑（包括一線骨髓纖維化標準療法魯索替尼）並不能靶向所有與骨髓纖維化相關的通路，包括 NF-κB、p53 和纖維化誘導通路。因此，使用 JAK 抑制劑單藥治療第一線骨髓纖維化患者並不能充分解決骨髓纖維化發病機制的相關驅動因素。

On slide 8, our confidence in selinexor's potential in myelofibrosis is based upon a growing body of preclinical, nonclinical, translational and clinical efficacy and safety data sets. These data suggest XPO1 inhibition is a key mechanism that may facilitate potential synergy with ruxolitinib and other drugs relevant in myelofibrosis.

在第 8 張投影片中，我們對 selinexor 在骨髓纖維化治療的潛力的信心是基於不斷增長的臨床前、非臨床、轉化和臨床療效和安全性資料集。這些數據表明，XPO1 抑制是一種關鍵機制，可能促進魯索替尼和其他與骨髓纖維化相關的藥物產生潛在的協同作用。

This multi-targeted approach enables treatment of the underlying mechanisms that lead to myelofibrosis, and we believe may lead to meaningful efficacy across the key treatment drivers as well as a generally safe and manageable side effect profile.

這種多標靶治療方法能夠治療導致骨髓纖維化的潛在機制，我們相信它能夠顯著改善關鍵治療因​​素，並帶來整體上安全且可控的副作用。

This is supported by our blinded safety data, which I will take you through in a few slides as well as our substantial safety database with selinexor, where approximately 30,000 patients have been treated in clinical trials and in the post-market setting. This underscores our confidence in the ongoing Phase III SENTRY trial.

我們的盲法安全性數據也支持這一點，我將在幾張投影片中向大家詳細介紹。此外，我們還有塞利尼索的大量安全性資料庫，其中約有 30,000 名患者在臨床試驗和上市後環境中接受了治療。這更加凸顯了我們對正在進行的 III 期 SENTRY 試驗的信心。

As seen on slide 9, while JAK inhibitors directly inhibit the JAK-STAT pathways, multiple other pathways downstream of JAK-STAT support malignant clone proliferation and survival, bone marrow fibrosis, cytokine storms and proliferation of abnormal megakaryocytes. These pathways include NF-kappa beta, PI3-kinase, AKT/mTOR, and TGF-beta, a multifaceted approach with dual XPO1 and JAK inhibition simultaneously target upstream and downstream effectors of the JAK-STAT pathway, ultimately enabling apoptosis or cell death of the malignant clones.

如幻燈片 9 所示，雖然 JAK 抑制劑直接抑制 JAK-STAT 通路，但 JAK-STAT 下游的多個其他通路支持惡性克隆增殖和存活、骨髓纖維化、細胞激素風暴和異常巨核細胞增殖。這些路徑包括 NF-κB、PI3激酶、AKT/mTOR 和 TGF-β，採用多方面方法，同時抑制 XPO1 和 JAK，靶向 JAK-STAT 路徑的上游和下游效應因子，最終導致惡性克隆細胞凋亡或死亡。

Let's now focus on the key treatment drivers in myelofibrosis as seen on slide 10, spleen reduction, symptom improvement and lower rates of Grade 3+ anemia. First, spleen volume reduction. As a reminder, note that only approximately one-third of patients achieved a spleen volume reduction of greater than 35% with ruxolitinib alone. In contrast, our Phase I data suggests that the combination could more than double the SVR35 rate at 79%. A substantial proportion of patients achieving an SVR35 is coupled with very encouraging durability, specifically a 100% duration of response as of the data cutoff.

現在讓我們專注於第 10 張投影片中所示的骨髓纖維化的關鍵治療驅動因素，即脾臟縮小、症狀改善和 3 級及以上貧血發生率降低。首先，縮小脾臟體積。需要提醒的是，僅使用魯索替尼治療的患者中，只有大約三分之一的患者脾臟體積縮小了 35% 以上。相較之下，我們的 I 期數據表明，該組合療法可以將 SVR35 率提高一倍以上，達到 79%。相當一部分達到 SVR35 的患者俱有非常令人鼓舞的持久性，特別是截至數據截止時，應答持續時間達到 100%。

Second is symptom improvement. Data from this trial also 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 points achieved by patients on ruxolitinib as observed in the Phase III MANIFEST-2 and TRANSFOR-1 trials. Third is lower rates of Grade 3+ anemia.

其次是症狀改善。該試驗的數據還顯示，第 24 週的絕對 TSS 平均改善了 18.5 分，這表明該組合療法可能比 III 期 MANIFEST-2 和 TRANSFOR-1 試驗中觀察到的魯索替尼治療患者所獲得的 11 至 14 分的改善更有意義。第三，3級以上貧血的發生率較低。

The data that we presented in June at EHA from our Phase II 035 monotherapy trial showed lower rates of all grade and Grade 3+ anemia in myelofibrosis patients previously treated with JAK inhibitor therapies. Blinded safety data from the ongoing Phase III SENTRY study suggests a similar trend.

我們在 6 月於 EHA 上發表的 II 期 035 單藥治療試驗數據顯示，在先前接受過 JAK 抑制劑治療的骨髓纖維化患者中，所有等級和 3 級及以上貧血的發生率均較低。正在進行的 III 期 SENTRY 研究的盲法安全性數據顯示，也存在類似的趨勢。

Meaningful improvement of these treatment drivers requires disease modification or the elimination of the underlying mechanisms leading to development of an enlarged spleen constitutional symptoms and worsening cytopenias.

要顯著改善這些治療驅動因素，需要改變疾病或消除導致脾臟腫大、全身性症狀和血球減少症惡化的潛在機制。

Data observed from selinexor monotherapy studies in a pretreated myelofibrosis population as well as our Phase I 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.

在接受過治療的骨髓纖維化患者中進行的 selinexor 單藥治療研究以及我們在 JAK 抑製劑初治骨髓纖維化患者中進行的 I 期聯合治療研究的數據表明，關鍵細胞因子（對骨髓纖維化發病機制、症狀發展和貧血至關重要）顯著減少，骨髓纖維化負荷得到改善，紅系祖細胞和突變負荷增加。

Turning to slide 11. We are super excited that our Phase III SENTRY trial has completed enrollment with top line data expected in March 2026. The co-primary endpoints in SENTRY are SVR35 and absolute TSS, which are tested sequentially. As we have discussed before, it is important to reemphasize based upon learnings from other myelofibrosis trials that we believe we have optimized SENTRY for success.

翻到第11張幻燈片。我們非常興奮地宣布，我們的 III 期 SENTRY 試驗已完成招募，預計將於 2026 年 3 月公佈主要數據。SENTRY 的共同主要終點是 SVR35 和絕對 TSS，這兩個終點是按順序測試的。正如我們之前討論過的，根據其他骨髓纖維化試驗的經驗，我們再次強調，我們相信我們已經優化了 SENTRY 試驗，使其成功。

In alignment with the FDA, we changed the co-primary endpoint of TSS50 to absolute TSS and exclude the fatigue domain in the primary analysis of absolute TSS due to the ambiguity of patients' assessment of their fatigue. We are certainly not the first to exclude fatigue. In fact, both the pivotal trials that led to ruxolitinib and fedratinib approvals also excluded fatigue in their TSS50 analyses.

為了與 FDA 保持一致，我們將 TSS50 的共同主要終點改為絕對 TSS，並且由於患者對自身疲勞的評估存在歧義，我們在絕對 TSS 的主要分析中排除了疲勞領域。我們當然不是第一個將疲勞排除在外的人。事實上，促成魯索替尼和費德拉替尼獲準的兩項關鍵試驗都在其 TSS50 分析中排除了疲勞因素。

Encouragingly, amongst approximately 350 patients enrolled in SENTRY, the mean baseline TSS, excluding fatigue is approximately 22.5. Note that the 21.9 that you will see in our ASH abstract today was preliminary data and before enrollment was completed. Our mean baseline of approximately 22.5 compares favorably to other comparable trials.

令人鼓舞的是，在 SENTRY 研究中入組的約 350 名患者中，不包括疲勞在內的平均基線 TSS 評分約為 22.5。請注意，您今天在我們 ASH 摘要中看到的 21.9 是初步數據，是在完成入組之前的數據。我們的平均基線值約為 22.5，與其他類似試驗相比，此數值具有優勢。

Importantly, as you compare our number to other trials, please remember other Phase III trials may include fatigue in their baseline scores. How does the fatigue domain affect the score? Given that in the Phase III MANIFEST-2 trial, the average fatigue score at baseline was approximately 5 points.

重要的是，在將我們的數據與其他試驗進行比較時，請記住其他 III 期試驗的基線評分中可能包括疲勞。疲勞程度如何影響評分？鑑於在 III 期 MANIFEST-2 試驗中，基線時的平均疲勞評分約為 5 分。

Our baseline score, if we included fatigue, would be approximately 5 points higher, which gives us confidence in the patient population that we have enrolled. Shifting back to our trial design, absolute TSS in the Phase III SENTRY trial will be analyzed using the mixed models repeated measure approach, or MMRM, which is viewed as a more sensitive and potentially more robust method by which to analyze absolute TSS.

如果將疲勞因素納入考量，我們的基線評分將提高約 5 分，這讓我們對所招募的患者群體充滿信心。回到我們的試驗設計，在 III 期 SENTRY 試驗中，絕對 TSS 將採用混合模型重複測量方法 (MMRM) 進行分析，該方法被認為是一種更靈敏、可能更穩健的絕對 TSS 分析方法。

Now let's review the encouraging preliminary blinded aggregate safety data from this trial. As these are preliminary and blinded data, please keep in mind that this data may not be reflective of the trial's actual top line results. The data on slide 12 are from the first 61 patients that enrolled in the Phase III portion of 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.

現在讓我們回顧一下這項試驗中令人鼓舞的初步盲法匯總安全性數據。由於這些數據是初步的、盲法的，請記住，這些數據可能無法反映試驗的實際主要結果。第 12 張投影片上的數據來自 SENTRY III 期研究中前 61 名入組患者，目前已對他們進行了超過 12 個月的中位追蹤。這些患者被納入了年初成功進行的無效性分析中。

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 continue to look favorable. The most common TEAEs are provided for the first 61 patients randomized to the trial and include patients randomized to both the combination of selinexor plus ruxolitinib or ruxolitinib arms in a 2:1 ratio. Because these are blinded data, we do not know the rates by each arm.

我們持續追蹤安全事件，並於 2025 年 7 月 1 日對這 61 名患者的盲法安全資料進行了快照，結果仍然令人滿意。試驗中隨機分配的前 61 名患者提供了最常見的治療期間出現的不良事件，其中包括以 2:1 的比例隨機分配到 selinexor 加 ruxolitinib 聯合治療組或 ruxolitinib 單藥治療組的患者。由於這些數據經過了盲法處理，我們無法得知各組的發生率。

In an effort to improve comparability, we then took our analysis one step further. Knowing that the 61 patients were randomized 2:1, we used 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 orange boxes in the middle 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 的比例隨機分組，我們利用魯索替尼的歷史數據推斷出接受聯合治療的約 40 名患者的初步安全性數據，這些數據在幻燈片中間的橙色方框中顯示。

The number that I am most optimistic by 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. Grade 3/4 thrombocytopenia rates are relatively similar, with 9% suggested for the combination treated patients compared with the approximately 6% reported for ruxolitinib alone.

我最樂觀的數字是 3/4 級貧血的推算率。此聯合療法的 3/4 級貧血發生率約為 26%，明顯低於魯索替尼歷史報告的 37%。3/4 級血小板減少症的發生率相對相似，合併治療組患者的發生率為 9%，而單獨使用魯索替尼治療的患者報告的發生率約為 6%。

Finally, the extrapolated rate of treatment-emergent adverse events leading to discontinuation is only approximately 5% to 7% for the combination, lower than the 6% to 11% range that has been historically reported from ruxolitinib, which we view as an encouraging observation. 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 III SENTRY trial.

最後，合併用藥導致治療中出現的不良事件的推算發生率僅為 5% 至 7%，低於魯索替尼歷史上報道的 6% 至 11% 的範圍，我們認為這是一個令人鼓舞的觀察結果。我們對這些數據以及如果在 III 期 SENTRY 試驗的主要結果中看到類似結果對患者可能意味著什麼感到非常鼓舞。

Specifically, it could suggest a combination therapy that has a safety profile similar, if not potentially better than standard of care ruxolitinib, given that both Grade 3 plus anemia and thrombocytopenia are similar, if not better, than ruxolitinib alone, could suggest decreased blood draws for the patient and reduced monitoring burdens for physicians and health care staff.

具體而言，鑑於 3 級及以上貧血和血小板減少症的發生率與單獨使用魯索替尼相似甚至更低，這可能提示聯合療法具有與標準治療魯索替尼相似甚至更好的安全性，這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。

As we await our Phase III data, it is informative to review a case study on slide 13 that shows meaningful efficacy, overall tolerability, and the potential for disease modification. This patient is enrolled in the Phase I combination study of selinexor and ruxolitinib and has been on the study treatment for over 3.5 years. This 81-year-old female was diagnosed with myelofibrosis secondary to polycythemia vera.

在我們等待 III 期數據之際，回顧第 13 張投影片上的案例研究很有幫助，該案例研究顯示了有意義的療效、整體耐受性和疾病改善的潛力。該患者參與了 selinexor 和 ruxolitinib 的 I 期聯合研究，並已接受研究治療超過 3.5 年。這位 81 歲的女性被診斷出患有真性紅血球增多症繼發的骨髓纖維化。

She initiated treatment with selinexor 60 milligrams in combination with ruxolitinib in March 2022. Her baseline spleen volume was 2,058 cubic centimeters for TSS without fatigue at baseline was 7, and variant allele frequency burden or VAF was 83%, meaning that 83% of her cells had a cancer-driving mutation.

2022 年 3 月，她開始接受 selinexor 60 毫克與 ruxolitinib 合併治療。她的基線脾臟體積為 2,058 立方厘米，基線時無疲勞的 TSS 為 7，變異等位基因頻率負荷或 VAF 為 83%，這意味著她 83% 的細胞具有癌症驅動突變。

She achieved an SVR35 and TSS50 at week 24 and complete resolution of her symptoms by approximately week 52. Furthermore, her VAF levels decreased to 0, signifying eradication of the cancer-driving mutation. To this day, she still continues on therapy with minimal side effects, with more than 3.5 years on therapy.

她在治療第 24 週達到 SVR35 和 TSS50，並在大約第 52 週時症狀完全緩解。此外，她的 VAF 水平降至 0，表明致癌突變已被根除。時至今日，她仍在接受治療，副作用極小，至今已接受治療超過 3.5 年。

This patient exemplifies the potential a multi-pathway approach can deliver in a disease as complex as myelofibrosis. XPO1 inhibitors' unique ability to simultaneously target multiple relevant pathways suggest their foundational potential in all patients with MS as well as other myeloproliferative neoplasms.

該患者充分體現了多途徑治療方法在治療骨髓纖維化這種複雜疾病方面所能發揮的巨大潛力。XPO1 抑制劑能夠同時針對多個相關通路，這種獨特的能力表明它們在所有 MS 患者以及其他骨髓增生性腫瘤患者中具有基礎性潛力。

I will now turn the call to Sohanya.

現在我將把電話轉給索哈尼亞。

Thank you, Reshma. As shown on slide 15, our commercial organization executed well this quarter within the highly competitive multiple myeloma market. XPOVIO net product revenue in Q3 grew 8.5% year-over-year to $32 million. Demand for XPOVIO was consistent year-over-year, with the community setting continuing to drive approximately 60% of total U.S. sales.

謝謝你，雷什瑪。如投影片 15 所示，本季我們的商業組織在競爭激烈的多發性骨髓瘤市場中表現出色。XPOVIO 第三季淨產品營收年增 8.5%，達到 3,200 萬美元。XPOVIO 的需求與去年同期保持穩定，社區環境持續推動美國總銷售額的約 60%。

XPOVIO is positioned in both the community and academic settings as a flexible therapy with a differentiated mechanism of action, oral convenient option, and increasingly used in the third line in patients before a T cell therapy or in patients who cannot access these complex therapies. Additionally, it is used in the fourth line plus setting once patients progress on a T cell therapy. Based on our results year-to-date, we are confident in our ability to deliver within our full year guidance range of $110 million to $120 million.

XPOVIO 在社區和學術環境中均被定位為一種靈活的療法，具有不同的作用機制，口服方便，並且越來越多地用於 T 細胞療法之前的患者的第三線治療，或用於無法獲得這些複雜療法的患者的治療。此外，當患者在 T 細胞療法中病情進展後，它還可用於第四線及以後的治療。根據我們今年迄今的業績，我們有信心實現全年1.1億美元至1.2億美元的業績目標。

Now turning to myelofibrosis outlined on slide 17. We are excited to be working towards a potentially transformative commercial launch that we expect will redefine the way that frontline myelofibrosis patients are treated. Our conviction is driven by the high unmet need in myelofibrosis, combined with the fact that there has been no real innovation in the market beyond JAK inhibitors over the past 14 years.

現在就來看看投影片 17 中概述的骨髓纖維化。我們很高興能夠致力於一項可能具有變革意義的商業發布，我們期望它能夠重新定義一線骨髓纖維化患者的治療方式。我們之所以如此堅信，是因為骨髓纖維化領域存在著巨大的未滿足需求，而且在過去 14 年裡，除了 JAK 抑制劑之外，市場上並沒有真正的創新。

Ruxolitinib has been the standard of care for more than a decade and is being used in the vast majority of intermediate to high-risk patients, even though fewer than 35% of these patients achieve an SVR35. Physicians and patients want to see deep and durable reduction in spleen volume.

魯索替尼已成為十多年來的標準治療方法，並用於絕大多數中高風險患者，儘管只有不到 35% 的患者能達到 SVR35。醫生和患者都希望看到脾臟體積大幅且持久地縮小。

And as Reshma discussed, the data from our Phase I trial highlights our potential in this area, with selinexor plus ruxolitinib helping more than twice as many patients achieving a spleen volume reduction of 35% or more. In addition, many patients experience constitutional symptoms and anemia, both of which negatively affect patient quality of life. And these are areas where we believe the selinexor plus ruxolitinib combination may make a meaningful difference. So, this presents us with a significant opportunity to improve upon the standard of care in combination with the market leader.

正如 Reshma 所討論的那樣，我們 I 期試驗的數據突顯了我們在該領域的潛力，selinexor 加 ruxolitinib 幫助超過兩倍的患者實現了脾臟體積減少 35% 或更多。此外，許多患者還會出現全身症狀和貧血，這兩種情況都會對患者的生活品質產生負面影響。我們認為，在這些領域，塞利尼索加魯索替尼聯合用藥可能會產生顯著效果。因此，這為我們提供了一個與市場領導者合作，提高護理標準的重要機會。

Slide 18 provides an overview of our potential commercial opportunity. We have the opportunity to redefine the standard of care, expand the market, and lead with a new frontline combination therapy that may offer very differentiated results for patients. This isn't an incremental change in the treatment landscape. It is a potentially transformational change for patients. Here are some figures that help inform our view that selinexor's peak revenue opportunity could be up to approximately $1 billion annually in the US.

第 18 張投影片概述了我們潛在的商業機會。我們有機會重新定義治療標準，擴大市場，並引領一種新的前線聯合療法，這種療法可能為患者帶來非常不同的治療效果。這並非治療領域的漸進式改變。這對患者來說可能是一項具有變革意義的改變。以下一些數據有助於我們理解，selinexor 在美國的高峰收入機會可能高達每年約 10 億美元。

If you look at the overall prevalent market, there are 20,000 patients living with myelofibrosis in the US, which represents a multibillion-dollar marketplace. As we look at the opportunity for patients that can benefit from selinexor plus ruxolitinib, there are approximately 4,000 newly diagnosed patients each year in the US with intermediate to high-risk myelofibrosis that have a platelet count above 100,000.

如果縱觀整個市場，美國有 2 萬名骨髓纖維化患者，這代表著一個價值數十億美元的市場。當我們檢視哪些患者可以從 selinexor 加 ruxolitinib 中獲益時，我們發現美國每年約有 4,000 名新確診的中高危險骨髓纖維化患者，他們的血小板計數超過 100,000。

This is our target market. Most of these patients receive ruxolitinib today. 75% of US physicians showed an intent to treat with combination therapy based on third-party market research. There is a clear appetite among physicians to evolve from a monotherapy to a combination treatment approach. Finally, the real-world duration of therapy for ruxolitinib is approximately 13 months. Our assumption is that the combination of selinexor plus ruxolitinib would be used for at least 13 months.

這是我們的目標市場。目前大多數此類患者接受魯索替尼治療。根據第三方市場調查，75%的美國醫生表示有意採用聯合療法治療這些患者。醫生們明顯希望從單一療法轉向聯合療法。最後，魯索替尼的實際治療持續時間約為 13 個月。我們假設 selinexor 加 ruxolitinib 的組合至少​​要使用 13 個月。

Looking at all of this together, you will see that our peak revenue opportunity may approach $1 billion annually in the US alone. As we prepare for potential commercialization, we have spent the past year speaking with leading KOLs at academic medical centers as well as community-based physicians and have received overwhelming support for the need to improve upon the current standard of care. Our position in the market, if approved, will be very clear and focused. If you're going to prescribe ruxolitinib to a patient with newly diagnosed myelofibrosis, prescribe selinexor plus ruxolitinib instead.

綜合以上所有因素來看，你會發現，光是在美國，我們的高峰收入機會就可能接近每年 10 億美元。在為潛在的商業化做準備的過程中，過去一年我們與學術醫療中心的領先KOL以及社區醫生進行了交流，並得到了他們對改進當前護理標準的強烈支持。如果獲得批准，我們在市場上的定位將非常清晰明確。如果要給新確診的骨髓纖維化患者開魯索替尼，請改為開塞利尼索加魯索替尼。

Finally, our existing commercial capabilities are highly synergistic in myelofibrosis and prepare us for a rapid and successful launch, as shown on slide 19. We have market access, a patient support hub, scientific and medical affairs, marketing, and a sales team with deep relationships with potential prescribers. In the academic setting, we already call on all the key institutions.

最後，我們現有的商業能力在骨髓纖維化領域具有高度協同效應，並為我們快速成功地推出產品做好了準備，如幻燈片 19 所示。我們擁有市場准入、患者支援中心、科學和醫學事務、行銷以及與潛在處方醫生建立深厚關係的銷售團隊。在學術領域，我們已經聯繫了所有關鍵機構。

In the community setting where a majority of newly diagnosed myelofibrosis patients are treated, there's approximately 80% overlap with our existing customer base. Pending positive data and subsequent regulatory approval, our commercial team will be ready to drive rapid and strong uptake as we bring this transformative therapy to patients.

在大多數新確診的骨髓纖維化患者接受治療的社區環境中，與我們現有客戶群的重疊率約為 80%。如果獲得積極數據和後續監管部門的批准，我們的商業團隊將做好準備，推動快速且強勁的市場推廣，將這種變革性療法帶給患者。

Now I'll turn the call over to Lori.

現在我把電話交給洛瑞。

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 21.

大家早安，謝謝索哈尼亞。接下來看一下財務數據。由於我們今天早些時候發布了包含完整財務業績的新聞稿，我將重點介紹亮點，並在第 21 頁回顧我們對 2025 年的指導意見。

Total revenue for the third quarter of 2025 was $44 million, an increase of 13.4% compared to $38.8 million in the third quarter of 2024. US XPOVIO net product revenue for the third quarter of 2025 was $32 million, an increase of 8.5% compared to $29.5 million in the third quarter of 2024. Gross to net provisions for XPOVIO were 27% in the third quarter, consistent with the second quarter of 2025 and down from 31% in the third quarter of 2024. We expect gross to net provisions to remain relatively consistent with the third quarter levels in the fourth quarter of 2025.

2025 年第三季總營收為 4,400 萬美元，比 2024 年第三季的 3,880 萬美元成長了 13.4%。美國 XPOVIO 公司 2025 年第三季淨產品收入為 3,200 萬美元，比 2024 年第三季的 2,950 萬美元成長了 8.5%。XPOVIO 第三季毛利淨利差為 27%，與 2025 年第二季持平，低於 2024 年第三季的 31%。我們預計 2025 年第四季毛撥備與淨撥備水準將與第三季水準保持相對一致。

License and other revenue was $12 million in the third quarter, up nearly 30% from third quarter of 2024, primarily driven by higher milestone revenue from our partner, Menarini. This included the final amount of revenue that we will record from Menarini related to the $15 million of annual R&D reimbursement. In the fourth quarter, our license and other revenue will primarily be royalty revenue since we do not expect to achieve any significant additional milestones in Q4 2025.

第三季授權和其他收入為 1,200 萬美元，比 2024 年第三季成長近 30%，主要得益於合作夥伴 Menarini 的里程碑收入增加。這其中包括我們將從 Menarini 確認的與 1500 萬美元年度研發報銷相關的最終收入金額。第四季度，我們的授權和其他收入將主要來自特許權使用費收入，因為我們預計在 2025 年第四季不會實現任何重大的額外里程碑。

Turning to expenses. We continue to be very disciplined in managing our operating expenses and prioritizing our pipeline investments, including additional cost reduction initiatives that we implemented in the third quarter. Research and development expenses for the third quarter of 2025 were $30.5 million, down 16% compared to $36.1 million in the third quarter of 2024.

接下來談談費用。我們繼續嚴格控制營運支出，優先考慮管道投資，包括我們在第三季實施的額外成本削減措施。2025 年第三季的研發費用為 3,050 萬美元，比 2024 年第三季的 3,610 萬美元下降了 16%。

The decrease was primarily driven by lower clinical trial and related costs for selinexor in multiple myeloma, reflecting the reduced scope of our Phase III trial, as well as lower personnel and stock-based compensation expenses resulting from previously implemented cost reduction initiatives.

此次下降主要歸因於塞利尼索治療多發性骨髓瘤的臨床試驗及相關成本降低，這反映了我們 III 期試驗範圍的縮小，以及先前實施的成本削減措施帶來的人員和股票補償費用的降低。

Selling, general, and administrative expenses were $26.6 million for the quarter, down 4% compared to $27.6 million in the third quarter of 2024. The decrease was primarily attributable to the continued realization of our cost reduction initiatives. Taken together, our loss from operations improved by approximately 42% in the third quarter of 2025 compared to the third quarter of 2024. Interest expense was $11 million in the third quarter of 2025 compared to $11.4 million in the third quarter of 2024.

本季銷售、一般及行政費用為 2,660 萬美元，比 2024 年第三季的 2,760 萬美元下降了 4%。下降的主要原因是成本削減措施的持續實施。綜合來看，2025 年第三季我們的營運虧損比 2024 年第三季減少了約 42%。2025 年第三季利息支出為 1,100 萬美元，而 2024 年第三季利息支出為 1,140 萬美元。

Other expense was $7.4 million in the third quarter of 2025 compared to $3.8 million of other income in the third quarter 2024. This nonoperational item is primarily driven by reoccurring noncash fair value remeasurements of embedded derivatives and liability classified common stock warrants related to the refinancing transactions completed in the second quarter of 2024.

2025 年第三季其他支出為 740 萬美元，而 2024 年第三季其他收入為 380 萬美元。此非經營性項目主要由與 2024 年第二季完成的再融資交易相關的嵌入式衍生性商品及負債分類普通股認股權證的經常性非現金公允價值重估所驅動。

We reported a net loss of $33.1 million or $3.82 per share on a GAAP basis. More than half of this loss is driven by below-the-line items, including interest expense, which is almost entirely noncash at this point and the $7.4 million of noncash mark-to-market adjustments that I just mentioned. Excluding these items, our underlying operating performance continues to show meaningful improvement.

根據美國通用會計準則（GAAP），我們報告淨虧損3,310萬美元，即每股虧損3.82美元。超過一半的損失是由以下項目造成的：利息支出（目前幾乎全部是非現金支出）以及我剛才提到的 740 萬美元的非現金按市值計價調整。剔除這些項目後，我們的基本經營績效持續呈現顯著改善。

Finally, prior to the receipt of approximately $36 million of gross proceeds from the financing transactions that we announced in October, we ended the third quarter with $46.2 million in cash, cash equivalents, restricted cash and investments compared to $109.1 million as of December 31, 2024.

最後，在我們於 10 月宣布的融資交易收到約 3,600 萬美元的總收益之前，截至第三季末，我們持有現金、現金等價物、受限現金和投資 4,620 萬美元，而截至 2024 年 12 月 31 日，這一數字為 1.091 億美元。

On a pro forma basis, after deducting transaction-related expenses, we would have had approximately $78 million in cash. Importantly, from a cash perspective, our interest payments do not start again until June 2026, and our royalty payments do not begin again until the third quarter of 2026.

以備考基準計算，扣除交易相關費用後，我們大約會有 7,800 萬美元現金。重要的是，從現金角度來看，我們的利息支付要到 2026 年 6 月才會再次開始，而我們的特許權使用費支付要到 2026 年第三季才會再次開始。

Based on our current operating plans, our guidance for the full year 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 年全年的業績預期如下：總收入為 1.4 億美元至 1.55 億美元，其中包括美國 XPOVIO 淨產品收入以及預計從我們的合作夥伴（主要是 Menarini 和 Antengene）獲得的許可費、特許權使用費和里程碑收入；美國 XPOVIO 1.1.2 億美元在 1.2 億美元之間預計收入。

We are lowering our range of R&D and SG&A expenses to $235 million to $245 million, down from $240 million to $250 million. With the financing that we announced last month, 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 into the second quarter of 2026.

我們將研發和銷售、一般及行政費用範圍從 2.4 億美元至 2.5 億美元下調至 2.35 億美元至 2.45 億美元。憑藉我們上個月宣布的融資，我們預計我們現有的流動資金，包括我們預計從 XPOVIO 淨產品銷售中獲得的收入以及從我們的許可協議中獲得的收入，將足以支持我們計劃的運營到 2026 年第二季度。

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，讓他做最後的總結。

Thank you, Lori. Before we close on slide 23, I want to emphasize how far Karyopharm has come and where we're heading. This quarter reflects clear execution against our priorities and the progress we've made has positioned us to enter 2026 with confidence. With SENTRY enrollment complete, a strong commercial foundation and a reinforced balance sheet, we are focused squarely on what matters most, delivering two potentially transformative Phase III readouts that could reshape the future for patients with myelofibrosis and endometrial cancer.

謝謝你，洛里。在結束第 23 張投影片之前，我想強調一下 Karyopharm 已經取得了多大的發展成就以及我們未來的發展方向。本季體現了我們在各項優先事項上的清晰執行，我們取得的進展使我們能夠充滿信心地邁入 2026 年。隨著 SENTRY 招募工作的完成、強大的商業基礎和穩健的資產負債表，我們正全力以赴地專注於最重要的事情，即提供兩項可能具有變革意義的 III 期研究結果，從而重塑骨髓纖維化和子宮內膜癌患者的未來。

Our team's dedication, scientific rigor and focus on patients continue to drive everything we do. We believe the opportunities ahead are significant, and we are executing with purpose and discipline to realize them.

我們團隊的奉獻精神、科學嚴謹性和對病人的關注，始終是我們一切工作的動力。我們相信未來的機會龐大，我們將以目標明確、嚴謹的態度去實現這些機會。

Thank you for your continued support and confidence in Karyopharm. We look forward to updating you as we advance towards these important milestones. I would now like to ask the operator to open the call up to the Q&A portion of today's call. Operator?

感謝您一直以來對Karyopharm的支持與信任。我們期待在邁向這些重要里程碑的過程中及時向您報告最新進展。現在我想請接線生開啟今天的問答環節。操作員？

(Operator Instructions) Peter Lawson, Barclays.

（操作說明）彼得·勞森，巴克萊銀行。

I guess first is just around the MF data that we're seeing March '26. If you could just kind of walk through what we should see if it's like SVR PFS and OS trends if that's going to be staged across other medical meetings in 2026. And then a follow-up question would just be around the size of the sales force. I know you've kind of talked about 80% overlap, but interested to see how many you would add or dedicate to MF and also the kind of the ex-US strategy.

我想首先要看的就是我們在 2026 年 3 月看到的 MF 數據。如果您能簡要介紹一下，如果像 SVR、PFS 和 OS 趨勢這樣的數據將在 2026 年的其他醫學會議上公佈，我們應該看到什麼，那就太好了。然後，後續問題可能就是關於銷售團隊的規模。我知道您之前提到過 80% 的重疊，但我很想知道您會增加多少或專門用於 MF，以及美國以外的策略是什麼。

Thanks, Peter. So maybe the first part, Peter, are you asking about when we plan to share the data post March? It wasn't quite clear the question in the first part.

謝謝你，彼得。所以，彼得，你是不是想問我們計劃在三月之後何時分享數據？第一部分的問題不太清楚。

Just the level of detail we'd see in -- for MF, whether it's SVR, TSS, OS trends and then -- or if it's spread across the year thing.

我們看到的細節程度——對於 MF 來說，無論是 SVR、TSS、OS 趨勢，還是它跨越全年的情況。

Sure. Yes, I'll turn to Reshma for that first part, and then I'll turn to Sohanya for the second part with regards to our commercial capabilities.

當然。是的，關於第一部分，我會請Reshma回答；關於我們的商業能力，我會請Sohanya回答第二部分。

Yes. Thanks, Peter. This is Reshma. So, the top line results, you're correct, expected more to 2026. I anticipate at this point, really just providing again sort of those top line details.

是的。謝謝你，彼得。這是雷什瑪。所以，整體結果，你說得對，預計到 2026 年會有更多成長。我預計此時此刻，真的只是再次提供一些主要細節。

So, you're correct, the primary endpoints of SVR35 at week 24, absolute TSS, potentially, right, some other secondary endpoints, including hemoglobin and/or disease modification. And then, of course, we'll touch upon safety. But we'll get granular as we get closer to that milestone.

所以，你說得對，主要終點是第 24 週的 SVR35、絕對 TSS，可能還有一些其他次要終點，包括血紅素和/或疾病改善。當然，接下來我們還會談到安全問題。但隨著我們越來越接近那個里程碑，我們會變得更加細緻。

Peter, as far as the sales force, as you mentioned, very strong overlap, particularly in the community setting, of course, with our current organization. And in the academic setting, we already call on those accounts. So, we expect really minimal additions to our commercial structure. Our capabilities are already highly synergistic. As far as ex-US, we'll continue to work with our ex-US partners to drive launches in each of the countries and additional royalty and milestone revenues globally.

Peter，就銷售團隊而言，正如你所提到的，與我們目前的組織相比，重疊度非常高，尤其是在社區環境中。在學術環境中，我們已經會用到這些帳戶。因此，我們預計商業結構不會有太大變化。我們雙方的能力已經高度互補。至於美國以外的地區，我們將繼續與美國以外的合作夥伴共同努力，推動產品在每個國家的上市，並在全球範圍內獲得額外的特許權使用費和里程碑收入。

Ted Tenthoff, Piper Sandler.

泰德·滕索夫，派珀·桑德勒。

Congrats on all the progress both on the clinical side and financial side. Can you remind us, are there any milestones associated with data or warrants or things like that for the recent financial restructuring that could extend that capital beyond the second quarter? And are there any geographies where you don't currently have distributors in place for myelofibrosis?

祝賀你們在臨床和財務方面都取得了進展。您能否提醒我們一下，最近的財務重組是否有任何與數據、認股權證或其他類似事項相關的里程碑，可以延長該筆資金的使用期限至第二季度之後？目前是否存在您尚未在骨髓纖維化領域設立經銷商的地區？

Thanks, Ted. Maybe on the first part, are you just asking about milestones from a financing perspective with regards to positive data? Or maybe just clarify that part of the question.

謝謝你，泰德。或許在第一部分，您只是從融資角度詢問有關積極數據的里程碑事件嗎？或者，或許可以把問題的這一部分解釋得更清楚一些。

Yes. So, milestones were there any warrants or anything like that, that could trigger to extend the June or the 2Q deadline. I was trying to remember back.

是的。那麼，里程碑事件中是否有任何條件或類似的事情，可能會觸發延長 6 月或第二季截止日期。我努力回想過去。

From a pure warrant or financing perspective, no specific triggers with regards to positive MF data. Obviously, pending positive data, we think that will be a very, very strong inflection and value point for us. And on the second part with regards to our partnerships globally, no, we have well-established partners for selinexor globally.

從純粹的認股權證或融資角度來看，與積極的共同基金數據相關的沒有具體觸發因素。顯然，在獲得正面數據之前，我們認為這將是我們股價的一個非常非常強勁的轉折點和價值點。至於第二部分，關於我們在全球範圍內的合作夥伴關係，不，我們在全球範圍內都有成熟的 selinexor 合作夥伴。

And as Sohanya mentioned, I think they're very excited and engaged and looking forward to positive data and moving forward with a registration strategy and commercialization strategy globally, which we would be able to do. With the exception, one market we still don't have partnered is Japan. That would be the only additional market we would look to partner with in the future moving forward.

正如 Sohanya 所提到的，我認為他們非常興奮，積極參與，期待獲得積極的數據，並在全球範圍內推進註冊戰略和商業化戰略，而我們也能夠做到這一點。除此之外，我們還沒有與日本市場建立合作關係。這將是我們未來唯一會考慮與之合作的市場。

Colleen Kusy, Baird.

科琳·庫西，貝爾德。

Congrats on all the progress. Hopeful for the baseline TSS number, 22.5%, I think you said, Reshma, quite a lot higher than what you had enrolled in the Phase I, I believe. And based on the data that you had at AACR in 2023, it actually looks like fairly similar response for TSS above and below 20, which could just be due to the small end, but just curious how you would expect that might impact the read-through from Phase I to the pivotal Phase III? And then I'll have a follow-up after.

祝賀你們取得的所有進展。雷什瑪，我想你說過，基線 TSS 數值為 22.5%，這比你在第一階段招募的數值要高得多。根據您在 2023 年 AACR 會議上提供的數據，TSS 高於和低於 20 時的反應似乎相當相似，這可能只是因為樣本量較小，但我很好奇您認為這會對從 I 期到關鍵性 III 期的解讀產生怎樣的影響？之後我還會跟進。

Yes. It's a great question, Colleen. I think we're very encouraged by how the baseline TSS is evolving. As you mentioned, 22.5%, approximately 22.5 in almost the full ITT. I think you're right.

是的。科琳，你問得好。我認為我們對基線 TSS 的發展感到非常鼓舞。正如您所提到的，22.5%，幾乎在整個 ITT 中約為 22.5%。我覺得你說得對。

Sort of the Phase I, it's small. So, we're very encouraged by those numbers. Clearly, it suggests that absolute TSS as well as TSS50 can be achieved with the combination relative to historical ruxolitinib data. I think what we were trying to accomplish in the Phase III was to drive that baseline TSS without fatigue as high as possible.

算是第一階段，規模很小。所以，我們對這些數字感到非常鼓舞。顯然，這表明相對於歷史魯索替尼數據，該聯合療法可以達到絕對 TSS 以及 TSS50。我認為我們在第三階段的目標是盡可能提高無疲勞狀態下的基線 TSS 值。

And so again, very encouraged with that 22.5%, especially as I compare it to other contemporary trials in which that 22.5 likely is higher than even those. So, it really suggests that we could see a potentially meaningful improvement for absolute TSS with our combination versus ruxolitinib alone.

因此，我對 22.5% 這個結果感到非常鼓舞，尤其是當我將其與其他同期試驗進行比較時，發現 22.5% 甚至可能高於其他試驗的結果。因此，這確實表明，與單獨使用魯索替尼相比，我們的聯合療法可能會在絕對 TSS 方面帶來潛在的顯著改善。

That's super helpful. And then in that same AACR update, it looks like there was some variability in response for platelet count above and below 200,000, which again could just be driven by small end. But curious if you have the baseline platelet count and what your kind of thoughts are on the activity based on platelet count.

這太有幫助了。然後在同一份 AACR 更新中，血小板計數高於和低於 200,000 時的反應似乎存在一些差異，這可能只是由較小的末端驅動的。但我很好奇您是否有基線血小板計數，以及您對基於血小板計數的活動有何看法。

Yes. We're seeing more than half of the patients with baseline platelet counts above 200 which again is what I would expect. There's nothing biological or mechanistic that would suggest that platelet count is a key variable that would impact the overall SVR35 rate or even the absolute PSS. So again, it's a number we're watching. It's a baseline characteristic that I think is very consistent with other Phase III trials.

是的。我們發現超過一半的患者基線血小板計數高於 200，這也在我的預期中。沒有任何生物學或機制上的證據表明血小板計數是影響整體 SVR35 率甚至絕對 PSS 的關鍵變數。所以，這是我們關注的數字。我認為這是一個基本特徵，與其他 III 期試驗非常一致。

In general, that variable as well as all of the other variables are in line with what we would expect and again, very encouraged with how this patient population is enrolled and who they represent across the frontline myelofibrosis population.

總的來說，該變數以及所有其他變數都符合我們的預期，並且再次強調，我們對該患者群體的招募方式以及他們代表的一線骨髓纖維化患者群體感到非常鼓舞。

Maurice Raycroft, Jefferies.

莫里斯‧雷克羅夫特，傑富瑞集團。

Congrats on the progress. So, ASH abstracts are coming out pretty soon. Just confirming, it sounds like your Phase III baseline data is going to be at ASH. Can you talk more about what's in the abstract and then what is going to be at the conference?

恭喜你取得進展。所以，ASH會議摘要很快就會公佈。確認一下，聽起來你們的 III 期基線數據將在 ASH 會議上公佈。能否詳細介紹摘要的內容以及會議的具體安排？

Yes. Thanks for the question, Maurice. So, the ASH, so it's going to be an abstract only. We're not going to present an additional poster. So, any additional data in the full ITT is going to be presented with the top line results in March of 2026.

是的。謝謝你的提問，莫里斯。所以，ASH會議只會是摘要。我們不會再展示其他海報。因此，完整的 ITT 中的任何附加數據都將與 2026 年 3 月的整體結果一起公佈。

So, when the data come out in about 20 minutes, really, what you're going to see is just the baseline characteristics amongst 320 patients. So, this is a subset. These were the available patients at the time of the data cutoff. And as I mentioned on my prepared remarks as well as with some of the questions today, just very encouraged with how that patient population has evolved and again, very consistent with what we would expect.

所以，大約 20 分鐘後數據出來的時候，你實際上看到的只是 320 名患者的基線特徵。所以，這是一個子集。這些是數據截止時可獲得的患者資訊。正如我在準備好的發言稿以及今天回答的一些問題中所提到的，我對患者群體的發展感到非常鼓舞，而且這與我們的預期非常一致。

And maybe as a follow-up, for the slightly lower treatment-emergent adverse events leading to discontinuation for the 61 patients in the blinded safety review. Can you comment on whether that rate is mostly in line with what you're seeing for the full study? I guess, any additional perspective there that you could share?

或許可以作為後續研究，針對盲法安全性審查中 61 名患者因治療期間出現的不良事件而導致停藥的情況，略有減少。您能否評論一下，這個比率是否與您在整個研究中觀察到的結果基本一致？我想問，您還有什麼其他見解可以分享嗎？

Yes, great question. So, one of the things that I'm very encouraged by is that we've followed these 61 patients and taken a snapshot across their AE summary, including their treatment discontinuation rates as well as the specific AEs as well as a couple of Grade 3 plus AEs. And what I'm encouraged by, again, is that despite whether we look at a seven-month median follow-up or even a 12-month median follow-up, rates, including treatment-emergent discontinuation rates are remarkably stable, right?

是的，問得好。因此，令我非常鼓舞的是，我們已經追蹤了這 61 名患者，並對他們的所有不良事件進行了總結，包括治療中斷率、具體不良事件以及一些 3 級及以上不良事件。令我感到鼓舞的是，無論我們觀察的是 7 個月的中位追蹤期還是 12 個月的中位追蹤期，包括治療期間出現的停藥率在內的各項指標都非常穩定，對吧？

So it really suggests that a majority of the events, including discontinuations potentially are occurring early, and we don't continue to see this accumulation as the patients are followed over time. Now what the top line results are going to show, we'll see at the top of the -- at the time that we report the top line results, but again, very encouraged by how the 61 patients are evolving.

所以這確實表明，大多數事件（包括停藥）可能發生在早期，而且隨著對患者的追蹤時間延長，我們並沒有繼續看到這種累積現象。現在，主要結果會顯示什麼，我們將在公佈主要結果時看到，但再次強調，我們對這 61 名患者的病情進展感到非常鼓舞。

Brian Abrahams, RBC Capital Markets.

Brian Abrahams，加拿大皇家銀行資本市場。

Congrats on all the progress. I wanted to drill down a little bit more on some of the market research findings, in particular, the high 75% intent to treat with the combo in frontline MF. I'm curious if you could talk a little bit more about sort of the types of patients that you're hearing physicians would try on a combo. Ruxolitinib initially, whether or not some of the payer feedback maybe you've been getting the early payer feedback has been aligned with what you're hearing from physicians in terms of the degree of frontline use.

祝賀你們取得的所有進展。我想更深入探討一些市場研究結果，特別是關於第一線 MF 聯合治療方案高達 75% 的意向治療情況。我很好奇您能否再詳細談談您聽說醫生們會嘗試對哪些類型的患者進行聯合治療。魯索替尼最初，無論你是否收到了一些支付方的回饋，早期支付方的回饋是否與你從醫生那裡聽到的關於一線使用程度的回饋一致。

And then with the space expected to evolve and more targeted treatments like mccarls and more targeted JAKs, what impact do you think that might have on the way selinexor is ultimately positioned should it be successful in Phase III?

隨著該領域的發展，以及像McCarls和JAKs這樣的標靶治療藥物的出現，您認為如果selinexor在III期臨床試驗中取得成功，這將對其最終定位產生什麼影響？

Yes. Thanks, Brian. Maybe I'll start kind of with the second part of your question, and I'll turn it over to Sohanya to talk to. I think broadly, in myelofibrosis, as you know and as Sohanya talked about, there's been really no new innovation in the front line, only JAK inhibition in myelofibrosis. So, there's significant opportunity across the whole space to improve outcomes for patients and to bring new innovation to patients, which is exactly what we're focused on.

是的。謝謝你，布萊恩。或許我可以先回答你問題的第二部分，然後把這個問題交給索哈尼亞來討論。我認為總的來說，正如你所知，也正如索哈尼亞所說，在骨髓纖維化領域，一線治療方面真的沒有什麼新的創新，只有JAK抑制劑用於治療骨髓纖維化。因此，整個領域都存在著巨大的機會來改善患者的治療效果，並為患者帶來新的創新，而這正是我們所關注的。

We're bringing a novel MOA such as selinexor and XPO1 inhibition, which we think can have a really meaningful benefit to patients. And when we look across the space again, I think the data we've shown, as we've talked about, we've been working on myelofibrosis for over seven-plus years. Reshma talked about the breadth of our data and showing impact as a monotherapy and obviously, as a combination.

我們正在引入一種新的作用機制，例如塞利尼索和 XPO1 抑制劑，我們認為這可以為患者帶來真正有意義的益處。當我們再次放眼整個領域時，我認為我們已經展示了數據，正如我們討論過的，我們已經研究骨髓纖維化超過七年了。Reshma 談到了我們數據的廣度，以及作為單一療法和聯合療法所展現的影響。

And I think what we're excited about, obviously, is to work to deliver that positive Phase III trial and then to continue expanding in MPNs as well as with selinexor, with eltanexor, our novel second-generation XPO1 inhibitor and a whole suite of XPO1 inhibitors that we have, which we think may be able to have an impact across a broad range of MPNs. With regards to the CALR, we need to wait.

顯然，我們感到興奮的是，我們將努力完成積極的 III 期試驗，然後繼續擴大在 MPN 領域的應用，同時我們還將使用 selinexor、eltanexor（我們新型的第二代 XPO1 抑製劑）以及我們擁有的一系列 XPO1 抑製劑，我們認為這些抑製劑可能對多種 MPN 產生影響。關於 CALR，我們需要等待。

We haven't seen any data in myelofibrosis. So again, I think there's a lot of opportunity for innovation and improvement. And what we're excited about again is in the very near-term to read out a potentially positive trial in a combination with such an impact for patients.

我們還沒有看到任何關於骨髓纖維化的數據。所以，我認為還有很多創新和改進的機會。我們再次感到興奮的是，在不久的將來，我們將公佈一項可能對患者產生重大影響的聯合療法的積極試驗結果。

And I'll let Sohanya talk to that because that's really what our market research indicates when we talk about the 75% intent to prescribe that combination therapy upfront for treatment-naive patients.

我會讓索哈尼亞來談談這個問題，因為我們的市場調查確實表明，對於初次接受治療的患者，有 75% 的人打算先開立這種聯合療法。

Thanks, Richard. Just to kind of add a little bit more to that. The target patient in the market research would be the newly diagnosed intermediate to high-risk patient with greater than 100,000 platelets. And the market research kind of just a little bit of background was comprised of both community and academic physicians. The proportions were in line with what we've seen in real world, the majority community physicians that are treating newly diagnosed myelofibrosis patients.

謝謝你，理查。只是想再補充一點。市場調查的目標患者是新確診的中高風險患者，其血小板計數超過 10 萬。市場調查方面，我們主要訪問了社區醫生和學術醫生，了解了一些背景資訊。這一比例與我們在現實世界中看到的情況一致，即大多數社區醫生正在治療新確診的骨髓纖維化患者。

So, the value proposition for selinexor is very simple, clear and focused. If a prescriber is already prescribing or planning to prescribe rux alone for a newly diagnosed myelofibrosis patient upon approval, they will then just do a seli plus rux combination. So, we are not competing with ruxolitinib, which is the standard of care go-to treatment for our target patient population. We're simply an addition with ruxolitinib, the current market leader. As we look at the sort of payer environment, we don't anticipate any kind of pushback with the payers.

因此，selinexor 的價值主張非常簡單、清晰且明確。如果處方醫生已經或計劃在獲得批准後單獨為新確診的骨髓纖維化患者開立魯西酮處方，那麼他們只需進行司來昔布加魯西酮的聯合治療即可。因此，我們並非與魯索替尼競爭，魯索替尼是我們目標患者群體的標準治療首選藥物。我們只是對目前市場領導者魯索替尼的一種補充。從支付方環境來看，我們預期不會遇到任何支付方的阻力。

And generally, as Richard pointed out, there really has been little innovation beyond the JAK inhibitors. So, there's a tremendous appetite to move these physicians from a monotherapy to a combination treatment approach.

正如理查德指出的那樣，總的來說，除了 JAK 抑制劑之外，真的沒有什麼創新。因此，人們非常希望這些醫生能夠從單一療法轉向聯合治療方法。

Jonathan Chang, Leerink.

Jonathan Chang，Leerink。

Just regarding the commercial potential launch in myelofibrosis, can you discuss any relevant learnings from the multi myeloma experience?

就骨髓纖維化領域的商業化潛力而言，您能否分享一下從多發性骨髓瘤的經驗中獲得的任何相關教訓？

Yes. I think broadly, Jonathan, the learnings from our multi myeloma experience really have been built in into the trial design, where in multi myeloma came to the marketplace, as you know, at a much higher dose at 80 milligrams twice weekly or 160 milligrams. And what we've learned over the past number of years is the importance and the ability to use selinexor at a lower dose.

是的。喬納森，我認為總的來說，我們從多發性骨髓瘤治療中學到的經驗教訓確實已經融入試驗設計中。你知道，多發性骨髓瘤藥物上市時的劑量要高得多，每週兩次 80 毫克，或 160 毫克。過去幾年我們了解到，使用較低劑量的塞利尼索非常重要且可行。

And we've obviously built that in with our trial now being at 60 milligrams once weekly. And we've also learned the importance of the dual antiemetics to use for the first couple of cycles as patients initiate therapy on XPO1 inhibition. We know that the nausea is transient and gets better over time. So, we've seen both those learnings over our multiple myeloma experience. We've built that in already to the design of the trial.

顯然，我們已經將這一點考慮在內，目前的試驗劑量為每週一次，每次 60 毫克。我們也了解到，在患者開始接受 XPO1 抑制劑治療的前幾個療程中，使用雙重止吐藥物非常重要。我們知道這種噁心是暫時的，隨著時間的推移會好轉。所以，我們在與多發性骨髓瘤抗爭的過程中，已經體會到了這兩方面的經驗教訓。我們已經在試驗設計中考慮到了這一點。

And so, I think moving forward and what we've seen already and what Reshma has shared in the blinded safety data is really the benefit to patients, the benefit overall to the tolerability profile. And as we saw from the very low TAE discontinuations, the benefit for patients.

因此，我認為展望未來，我們已經看到的以及 Reshma 在盲法安全性數據中分享的內容，真正對患者有益的是整體耐受性方面的益處。從 TAE 治療中斷率極低的情況來看，患者從中受益匪淺。

And I think the case study Reshma talked to with the patient on the combination for over 3.5 years and so benefiting really talks to the outcomes for patients from those learnings we've built in. So, we feel very positive about the learnings we've built in and the potential to transform outcomes for myelofibrosis patients in the front line.

我認為，雷什瑪與患者就該聯合療法進行了長達 3.5 年的案例研究，患者從中受益，這真正體現了我們從這些經驗中學到的知識對患者帶來的療效。因此，我們對已累積的經驗以及改變第一線骨髓纖維化患者治療結果的潛力感到非常樂觀。

Yes. I would add that the kind of biggest differentiating point between the two landscapes is the degree of competition. Myeloma, highly competitive with overlapping competitors across classes, very different situation in myelofibrosis, really little to no innovation beyond the JAK inhibitors. Also, I would say the myelofibrosis space is primed to be what the myeloma space was over a decade ago. Over a decade ago in myeloma, they were using monotherapies and then evolving to doublets.

是的。我想補充的是，這兩種景觀之間最大的差異在於競爭程度。多發性骨髓瘤的競爭非常激烈，各類別的競爭對手都有重疊；而骨髓纖維化的情況則截然不同，除了 JAK 抑制劑之外，幾乎沒有任何創新。另外，我認為骨髓纖維化領域已經準備好像十多年前的骨髓瘤領域一樣。十多年前，在多發性骨髓瘤的治療中，他們先使用單藥療法，然後逐漸發展到雙藥療法。

That is the level of transformation, I think we're about to see in myelofibrosis. The second point is given that we have established a commercial organization that has worked very closely with community physicians who will be the majority of prescribers for the newly diagnosed patients, there's a high degree of synergy, and we expect to launch rapidly with myelofibrosis.

我認為，這就是骨髓纖維化即將發生的轉變。第二點是，我們已經建立了一個商業組織，該組織與社區醫生密切合作，而社區醫生將是新確診患者的主要處方醫生，因此存在高度協同效應，我們預計骨髓纖維化治療將迅速啟動。

And that concludes today's question-and-answer session. I would like to turn it back to Richard Paulson for closing remarks.

今天的問答環節到此結束。我謹將發言權交還給理查德·保爾森，請他作總結發言。

Thank you, operator, and thank you to everyone again for joining us on today's call. As you can tell, we are very excited about our prospects to redefine the current standard of care for the majority of frontline myelofibrosis patients. We look forward to sharing top line data with you in March and pending future regulatory approvals, our organization is well prepared to rapidly deliver on the commercial opportunity. Once again, thanks for joining today.

謝謝接線員，也再次感謝各位參加今天的電話會議。正如您所看到的，我們對重新定義目前大多數第一線骨髓纖維化患者的護理標準充滿信心。我們期待在三月與您分享初步數據，並且，在獲得未來監管部門的批准後，我們公司已做好充分準備，迅速抓住商業機會。再次感謝您今天的參與。

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

謝謝。女士們、先生們，今天的電話會議到此結束。感謝各位的參與。您現在可以斷開連線了。