Karyopharm Therapeutics Inc. (KPTI) 2026 Q2 法說會逐字稿

Good morning. My name is Anas, and I'll be your conference operator today. At this time, I would like to welcome everyone to Karyopharm's second-quarter 2026 financial results conference call. (Operator Instructions)

早安。我叫 Anas，今天將擔任本次會議的接線員。此刻，我謹代表公司歡迎各位參加 Karyopharm 2026 年第二季財務業績電話會議。(接線員指示)

Please be advised that this call is being recorded at the company's request. I would now like to turn the conference over to Brandon Strong, Senior Vice President, Investor Relations.

請注意，應公司要求，本次通話將被錄音。現在我想將會議交給投資人關係資深副總裁 Brandon Strong。

Good morning, and thank you all for joining us on today's conference call to discuss Karyopharm's second quarter 2026 financial results and recent company progress. We issued a press release this morning detailing our financial results for the second quarter of 2026. This release, along with the slide presentation that we will reference during our call today, are available on our website.

早安，感謝各位參加今天的電話會議，一同討論 Karyopharm 2026 年第二季財務業績以及公司近期進展。我們今早已發布新聞稿，詳述 2026 年第二季的財務結果。該新聞稿以及我們今天通話中將引用的簡報投影片，均可於公司網站取得。

For today's call, as shown on slide 2, I'm joined by Richard, Reshma, Sohanya, and Lori, who will review our second quarter financial results, provide an update on the significant progress we've made advancing our myelofibrosis program, discuss the clinical and regulatory momentum supporting our planned sNDA submission, and review our financial position and capital allocation priorities.

就今天的會議而言，如投影片 2 所示，我與 Richard、Reshma、Sohanya 以及 Lori 一同出席；他們將回顧我們第二季的財務結果，更新我們在推進骨髓纖維化計畫方面所取得的重大進展，討論支持我們規劃提交 sNDA 的臨床與法規動能，並回顧我們的財務狀況與資本配置優先事項。

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.

在開始正式發言之前，我要提醒各位，我們今天的部分陳述構成前瞻性聲明，適用於 1995 年《私人證券訴訟改革法案》之安全港條款，如投影片 3 所述。

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 we may make with the SEC in the future. Any forward-looking statements represent our views as of today only.

由於多項重要因素，實際結果可能與這些前瞻性聲明所示存在重大差異，包括我們最近提交給美國證券交易委員會（SEC）的 Form 10-Q 或 10-K 中風險因素章節所討論者，以及我們未來可能向 SEC 提交的其他文件中所述因素。任何前瞻性聲明僅代表我們截至今日的觀點。

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.

雖然我們未來可能選擇在某個時間點更新這些前瞻性聲明，但即使我們的觀點有所改變，我們亦明確聲明不負有任何更新義務。因此，您不應依賴這些前瞻性聲明作為我們在任何較晚日期之觀點的代表。接下來我把電話交給 Richard。

Please turn to slide 5.

請翻到投影片 5。

Thank you, Brandon, and good morning, everyone, and thank you for joining us today. The second quarter marked the beginning of an important new chapter for Karyopharm as we advanced selinexor from a compelling and differentiating Phase 3 data set toward our planned supplemental new drug application under the FDA's Accelerated Approval Pathway for patients with myelofibrosis.

謝謝你，Brandon。各位早安，也感謝各位今天加入我們。第二季標誌著 Karyopharm 開啟重要新篇章：我們正將 selinexor 從一套具說服力且具差異化的第三期數據，推進至我們規劃依據 FDA 加速核准途徑（Accelerated Approval Pathway）為骨髓纖維化患者提交的補充新藥申請（sNDA）。

Over the past several months, we've remained focused, moved with urgency, and executed against an ambitious plan, generating and presenting the SENTRY data, publishing the results in the Journal of Clinical Oncology, working collaboratively with the FDA to establish a regulatory pathway as we prepare our planned submission.

在過去幾個月中，我們始終保持專注、以緊迫感推進，並執行一項具雄心的計畫：產出並發表 SENTRY 數據、在《臨床腫瘤學期刊》（Journal of Clinical Oncology）發表結果，並與 FDA 協作建立法規途徑，同時為我們規劃的申請提交做準備。

The SENTRY study demonstrated statistically significant, rapid, deep, and sustained spleen responses, together with preliminary overall survival findings and evidence of potential disease modification. These findings have now been presented at leading international scientific meetings, published in a peer-reviewed journal, and continue to generate strong interest globally among the hematology community.

SENTRY 研究顯示脾臟反應在統計上顯著，且反應快速、幅度深且可持續；同時亦有初步的整體存活期發現，以及可能具疾病修飾作用的證據。這些發現已在重要的國際科學會議上發表，並刊登於同儕審查期刊，持續在全球血液學界引發高度關注。

Taken together, we believe these data reinforce the potential for selinexor to fundamentally change the treatment of patients with myelofibrosis. That same focus, urgency, and commitment to execution continues to guide every step as we advance into the next phase of our myelofibrosis program.

綜合而言，我們相信這些數據進一步強化 selinexor 有潛力從根本上改變骨髓纖維化患者的治療方式。同樣的專注、緊迫感與執行承諾，將持續引導我們在骨髓纖維化計畫下一階段的每一步。

Turning to slide 6, as we announced in July, we remain on track to submit our sNDA in August as we complete the final elements of our submission in collaboration with the FDA. Our interactions with the agency continue to be constructive, and we remain focused on delivering a high-quality submission.

接著看投影片 6，如我們在 7 月所宣布，我們仍按計畫於 8 月提交 sNDA，並在與 FDA 協作下完成提交所需的最後要素。我們與主管機關的互動持續具建設性，我們也仍專注於提交高品質的申請資料。

Our confidence in this opportunity continues to be grounded in both the consistency of the SENTRY data and our constructive regulatory engagement. If approved, selinexor in combination with ruxolitinib would be the first approved combination therapy for patients with myelofibrosis, introducing a novel therapeutic mechanism for the treatment of this disease.

我們對此機會的信心，持續建立在 SENTRY 數據的一致性以及我們具建設性的法規互動之上。若獲核准，selinexor 與 ruxolitinib 的合併療法將成為首個獲核准用於骨髓纖維化患者的合併治療，並為此疾病的治療引入一種新穎的治療機制。

Turning to slide 7, while our focus today is on the important progress we've made in myelofibrosis, I'd also like to briefly address the top-line results from our Phase 3 XPORT-EC-042 study and the actions we've taken following those results.

接著看投影片 7，雖然我們今天的重點是骨髓纖維化方面的重要進展，我也想簡要說明我們第三期 XPORT-EC-042 研究的主要結果，以及我們在結果公布後所採取的行動。

While we were disappointed that the study did not achieve statistical significance for its primary endpoint in the mITT population, I want to thank the patients, investigators, and study teams whose commitment made this important trial possible. Although we observed a numerical improvement in median progression-free survival favoring selinexor, the study did not meet the statistical threshold required to support our development plans in endometrial cancer.

雖然我們對該研究在 mITT 族群未能於主要終點達到統計顯著性感到失望，但我要感謝所有患者、研究者與研究團隊；正是他們的投入使這項重要試驗得以完成。儘管我們觀察到中位無惡化存活期（PFS）在數值上改善且偏向 selinexor，但該研究未達到支持我們在子宮內膜癌開發計畫所需的統計門檻。

Following these results, we made the deliberate decision to sharpen our focus on hematology with our opportunities in myelofibrosis and multiple myeloma, where we believe selinexor has the greatest potential to improve patients' lives and create long-term shareholder value.

在這些結果之後，我們審慎決定將重心更聚焦於血液腫瘤領域，鎖定骨髓纖維化與多發性骨髓瘤的機會；我們相信在這些領域 selinexor 最有潛力改善患者生活並創造長期股東價值。

While we continue to follow patients in the near term, we are meaningfully reducing planned investment in endometrial cancer. Moving forward, our priorities are clear. Advancing our myelofibrosis program through the regulatory process, continuing to grow our multiple myeloma business, and leveraging the commercial, medical, and market access capabilities we have built over many years to a rapid and efficient launch in myelofibrosis if approved.

在短期內我們仍將持續追蹤患者，但我們將大幅降低原先規劃在子宮內膜癌上的投資。展望未來，我們的優先事項很明確。推進骨髓纖維化計畫完成法規流程、持續成長我們的多發性骨髓瘤業務，並運用我們多年建立的商業化、醫學與市場准入能力，在若獲核准的情況下，於骨髓纖維化領域進行快速且高效率的上市推廣。

As we execute against these priorities, we are equally focused on disciplined capital allocation. As we'll discuss, we are actively evaluating a range of financing opportunities and strategic alternatives with the objective of maximizing long-term shareholder value while preserving strategic flexibility as we advance our myelofibrosis program through these important milestones.

在執行這些優先事項的同時，我們也同樣重視嚴謹的資本配置。如我們將討論的，我們正積極評估多元的融資機會與策略替代方案，目標是在推進骨髓纖維化計畫達成這些重要里程碑的同時，最大化長期股東價值並保留策略彈性。

We are approaching this with the same focus, urgency, and discipline that have characterized our execution over the past several months. Looking ahead, we believe the company is entering one of the most important periods in its history.

我們將以過去幾個月一貫的專注、緊迫感與紀律來推進此事。展望未來，我們相信公司正進入其歷史上最重要的時期之一。

Turning to slide 8, over the coming quarters we expect several important milestones, beginning with the potential inclusion in the treatment guidelines in Compendia, our planned sNDA submission in myelofibrosis this month, followed by potential FDA filing acceptance of the sNDA, and its potential to be accepted for priority review and ultimately a potential approval and launch as early as the first quarter of 2027.

接著看投影片 8，在接下來幾個季度，我們預期將迎來數個重要里程碑：首先可能納入 Compendia 的治療指引；本月我們規劃提交骨髓纖維化的 sNDA；接著可能獲 FDA 受理（filing acceptance）；並可能被接受優先審查，最終可能在最早 2027 年第一季獲核准並上市。

Additionally, we remain on track to report top-line data from the 60 milligram cohort of the Phase 2 SENTRY-2 study in the second half of this year, which we expect will further establish the role of selinexor in myelofibrosis. We are entering this next phase with a clear strategy, a focused organization, and an established hematology platform that positions us well for what lies ahead.

此外，我們仍按計畫於今年下半年公布第 2 期 SENTRY-2 研究 60 毫克劑量隊列的主要數據，我們預期這將進一步確立 selinexor 在骨髓纖維化中的角色。我們以明確的策略、聚焦的組織，以及既有的血液腫瘤平台進入下一階段，這使我們能為未來的挑戰做好充分準備。

With that, I'll turn the call over to Reshma, who will discuss the clinical and regulatory foundations supporting our planned submission for the first ever combination and why we believe selinexor is a necessary novel therapeutic mechanism that has the potential to fundamentally change the treatment of patients with myelofibrosis. Reshma?

接下來，我把電話交給 Reshma，她將說明支持我們規劃中首次聯合療法申請的臨床與法規基礎，以及為何我們相信 selinexor 是一種必要的新型治療機制，具有從根本上改變骨髓纖維化患者治療方式的潛力。Reshma？

Thank you, Richard. As Richard discussed, we believe selinexor has the potential to fundamentally change the treatment of patients with myelofibrosis. I'd like to spend the next few minutes discussing why we believe the scientific evidence supporting that opportunity has continued to strengthen, why it supports our planned sNDA submission, and how we continue to build the clinical foundation for selinexor in myelofibrosis.

謝謝你，Richard。如 Richard 所述，我們相信 selinexor 有潛力從根本上改變骨髓纖維化患者的治療。接下來幾分鐘，我想談談為何我們認為支持此機會的科學證據持續增強、為何其支持我們規劃中的 sNDA 送件，以及我們如何持續建立 selinexor 在骨髓纖維化的臨床基礎。

Turning to slide 10, the biological rationale for combining XPO1 and JAK inhibition is compelling. STAT activation is a key driver of malignant clone proliferation, splenomegaly, and disease-related symptoms, while XPO1 activity is important for malignant cell survival. By targeting these complementary pathways simultaneously, we believe selinexor has the potential to complement JAK inhibition and improve outcomes beyond symptom control alone.

請看第 10 張投影片，將 XPO1 抑制與 JAK 抑制合併的生物學理據相當有說服力。STAT 活化是惡性克隆增殖、脾腫大與疾病相關症狀的關鍵驅動因素，而 XPO1 活性對惡性細胞存活也很重要。透過同時鎖定這些互補路徑，我們相信 selinexor 有潛力補強 JAK 抑制，並將療效提升至不僅止於症狀控制。

Turning to slide 11, myelofibrosis remains a disease with a high unmet need given clinical activity with the currently approved therapies is modest. As a result, spleen volume reduction of at least 35% is observed in less than one-third of patients. Overall survival improvements are limited, and meaningful modifications of the underlying disease is not observed.

請看第 11 張投影片，骨髓纖維化仍是一種高度未被滿足醫療需求的疾病，因為目前已核准療法的臨床活性有限。因此，脾臟體積至少縮小 35% 的情況在不到三分之一的患者中觀察到。整體存活期的改善有限，且未觀察到對基礎疾病的有意義改變。

Turning to slide 12, a distinctive profile has been observed from the SENTRY trial, given the compelling SVR35 results that are rapid, deep, and sustained, a promising OS signal, a first-of-a-kind prediction between SVR35 and OS, and a safe and manageable adverse event profile. These data appear to support SVR35 as a reasonably likely surrogate endpoint, enabling an sNDA under the accelerated approval pathway.

請看第 12 張投影片，SENTRY 試驗觀察到一個具特色的療效與安全性概況：SVR35 結果具說服力，反應快速、幅度深且可持續；整體存活期（OS）出現令人鼓舞的訊號；首次建立 SVR35 與 OS 之間的預測關係；且不良事件概況安全且可管理。這些數據似乎支持 SVR35 作為「合理可能」的替代終點（surrogate endpoint），使得可在加速核准途徑下提出 sNDA。

Turning to slide 13, at week 24, a nearly double spleen response rate was observed with the combination of selinexor plus ruxolitinib versus ruxolitinib alone. What's particularly important is the quality and kinetics of that response. As shown on slide 14, the responses were rapid, emerging as early as week 12, and deep, with greater average spleen volume reductions relative to baseline observed with the combination. Both response rates and depth of response were sustained through week 36.

請看第 13 張投影片，在第 24 週，selinexor 加上 ruxolitinib 的合併治療，相較於單用 ruxolitinib，觀察到近乎加倍的脾臟反應率。特別重要的是該反應的品質與動態。如第 14 張投影片所示，反應快速，最早在第 12 週即出現；且反應更深，合併治療相較基線的平均脾臟體積縮小幅度更大。反應率與反應深度皆可維持至第 36 週。

Importantly, as seen on slide 15, the benefit was consistent across pre-specified patient subgroups, reinforcing the robustness of the treatment effect in the vast majority of frontline myelofibrosis patients. Especially important is a subgroup analysis by ruxolitinib dosing as seen on slide 16. Even with average suboptimal doses of ruxolitinib less than 15 milligrams per day, SVR35 rates with the combination were as high as 50% compared to zero observed with ruxolitinib alone, indicating that with the combination, SVR35 is driven by selinexor and supported by modest doses of ruxolitinib.

重要的是，如第 15 張投影片所示，療效在預先指定的患者亞組中一致，強化了治療效果在絕大多數一線骨髓纖維化患者中的穩健性。同樣特別重要的是如第 16 張投影片所示、依 ruxolitinib 劑量進行的亞組分析。即使 ruxolitinib 的平均劑量偏低、低於每日 15 毫克，合併治療的 SVR35 比例仍高達 50%，而單用 ruxolitinib 則為 0%，顯示在合併治療下，SVR35 主要由 selinexor 驅動，並由中等劑量的 ruxolitinib 所支持。

From a clinical practice standpoint, these data suggest that ruxolitinib dose reductions may not compromise efficacy when combined with selinexor. As shown on slide 17, at the time of the top-line analysis, the overall survival hazard ratio was 0.43, and patients continued to be followed as these data mature.

從臨床實務角度來看，這些數據顯示，當與 selinexor 合併使用時，降低 ruxolitinib 劑量可能不會犧牲療效。如第 17 張投影片所示，在主要分析時點，整體存活期的風險比（hazard ratio）為 0.43，且隨著數據成熟，患者仍持續追蹤中。

On slide 18, a post hoc landmark analysis demonstrated that irrespective of treatment, SVR35 at week 24 predicted overall survival. This observation is further reinforced by the longer term follow up from the Phase 1 trial on slide 19, in which the same relationship between SVR35 and overall survival is observed. On slide 20, the importance of the SVR35-OS relationship becomes even clearer when viewed in the context of the broader myelofibrosis literature.

在第 18 張投影片，一項事後（post hoc）地標分析顯示，不論接受何種治療，第 24 週達到 SVR35 可預測整體存活期。此觀察結果亦由第 19 張投影片所示第 1 期試驗的較長期追蹤進一步支持，其中同樣觀察到 SVR35 與整體存活期之間的關係。在第 20 張投影片，當把 SVR35 與 OS 的關係放在更廣泛的骨髓纖維化文獻脈絡中來看，其重要性更為清楚。

Over the past several years, a substantial body of retrospective evidence from Phase 3 JAK inhibitor trials has demonstrated that greater SVR35 rate differences observed across the two arms correlate with improved overall survival. SENTRY now provides an important opportunity to build on that body of evidence as the first Phase 3 trial that prospectively demonstrates the same relationship and establishes SVR35 as a potential surrogate endpoint for overall survival. This underscores the importance of treating patients with the combination early in the disease course, increasing the likelihood an SVR35 reduction is observed, thus potentially maximizing overall survival.

過去數年，大量來自第 3 期 JAK 抑制劑試驗的回溯性證據顯示，兩組之間觀察到的 SVR35 比例差異越大，與整體存活期改善的相關性越高。SENTRY 現在提供了一個重要機會，在此證據基礎上更進一步：它是首個以前瞻性方式證實相同關係的第 3 期試驗，並將 SVR35 建立為整體存活期的潛在替代終點。這也凸顯在疾病早期以合併療法治療患者的重要性，提高觀察到 SVR35 降低的可能性，從而可能最大化整體存活期。

On slide 21, we also observed higher rates of variant allele frequency reduction with selinexor plus ruxolitinib as early as week 24. These molecular findings are important because VAF reduction was associated with a greater likelihood of achieving SVR35, providing additional biological evidence that is consistent with the clinical findings.

在第 21 張投影片，我們也觀察到 selinexor 加上 ruxolitinib 在第 24 週即呈現較高的變異等位基因頻率（VAF）下降比例。這些分子層面的發現很重要，因為 VAF 下降與更高的 SVR35 達成機率相關，提供了與臨床結果一致的額外生物學證據。

Taken together on slide 22, the rapid, deep, and sustained spleen responses, the promising overall survival findings, the relationship between SVR35 and survival, and the molecular data all point in the same direction. We believe this unique and compelling profile strengthens the scientific rationale for SVR35 as a meaningful predictor of long-term survival.

綜合第 22 張投影片所示，快速、深度且可持續的脾臟反應、令人鼓舞的整體存活期結果、SVR35 與存活之間的關係，以及分子數據，都指向同一方向。我們相信這一獨特且具說服力的概況，強化了 SVR35 作為長期存活之有意義預測指標的科學理據。

It is the combination of this growing body of evidence, the strength of the SENTRY data, and the significant unmet need in myelofibrosis that formed the basis of our scientific discussions with the FDA regarding the role of SVR35 in supporting our planned sNDA submission.

正是這些日益累積的證據、SENTRY 數據的強度，以及骨髓纖維化顯著的未被滿足醫療需求，共同構成了我們與 FDA 就 SVR35 在支持我們規劃中的 sNDA 送件所扮演角色進行科學討論的基礎。

We believe the FDA's written feedback indicating that SVR35 appears to qualify as a reasonably likely surrogate endpoint to predict overall survival represents an important scientific and regulatory milestone. Importantly, this builds upon years of scientific evidence supporting the relation between SVR35 and long-term outcomes, together with the prospective randomized evidence generated through SENTRY.

我們認為，FDA 的書面回饋指出 SVR35 似乎符合「合理可能」的替代終點資格、可用以預測整體存活期，這代表一項重要的科學與法規里程碑。重要的是，這是建立在多年支持 SVR35 與長期結局之關聯的科學證據之上，並結合由 SENTRY 所產生的前瞻性隨機分派證據。

Our planned submission will be based on the week 24 SVR35 results. We intend to use additional long-term overall survival data from the ongoing SENTRY trial to verify clinical benefit, a requirement under the accelerated approval pathway to later convert to traditional approval.

我們規劃中的送件將以第 24 週的 SVR35 結果為基礎。我們擬使用正在進行中的 SENTRY 試驗所提供的額外長期整體存活期數據來驗證臨床效益；在加速核准途徑下，這是日後轉為傳統核准所需的要求。

While our immediate priority is our planned submission, we continue to explore the broader role of selinexor in myelofibrosis. On slide 23, the ongoing SENTRY-2 study provides an opportunity to further characterize the activity of selinexor as a monotherapy and explore the potential flexibility of XPO1 inhibition in combination with additional JAK inhibitors. This study will help us better understand the intrinsic contribution of selinexor and continue to define the broader role of XPO1 inhibition across the treatment of patients with myelofibrosis.

雖然我們眼前的首要任務是按計畫提交申請，但我們仍持續探索 selinexor 在骨髓纖維化中的更廣泛角色。在第 23 張投影片中，正在進行的 SENTRY-2 研究提供了一個機會，可進一步刻畫 selinexor 作為單藥治療的活性，並探索 XPO1 抑制在與其他 JAK 抑制劑聯合使用時的潛在彈性。此研究將協助我們更深入了解 selinexor 的內在貢獻，並持續界定 XPO1 抑制在骨髓纖維化患者治療中的更廣泛角色。

As Richard noted, we expect top-line data from the 60-milligram cohort of SENTRY-2 during the second half of this year. We believe the strength and consistency of the evidence generated through SENTRY, together with our continued clinical development efforts, provide a strong scientific foundation for our planned sNDA submission, and reinforce our belief that selinexor has the potential to fundamentally change the treatment of patients with myelofibrosis.

如 Richard 所提到，我們預期將於今年下半年取得 SENTRY-2 之 60 毫克劑量隊列的主要（top-line）數據。我們相信，SENTRY 所產生證據的強度與一致性，加上我們持續的臨床開發努力，為我們計畫提交的 sNDA 申請提供了堅實的科學基礎，並強化我們的信念：selinexor 有潛力從根本上改變骨髓纖維化患者的治療。

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

接下來，我把電話會議交給 Sohanya。

Thank you, Reshma. Turning to slide 25, my focus today is on why we believe Karyopharm is well positioned to commercialize this opportunity. Importantly, we're not preparing to build a commercial organization from the ground up. We're leveraging an established hematology platform that we have built over many years through the commercialization of XPOVIO. On the scientific side, we have clinical development experience, active medical and scientific affairs teams, investigative relationships, and growing visibility across the myelofibrosis community.

謝謝你，Reshma。請看第 25 張投影片，我今天的重點在於我們為何相信 Karyopharm 已具備良好條件將此機會商業化。重要的是，我們並非要從零開始建立商業組織。我們正運用多年來透過 XPOVIO 商業化所建立的既有血液腫瘤平台。在科學面，我們具備臨床開發經驗、活躍的醫學與科學事務團隊、研究者合作關係，以及在骨髓纖維化社群中日益提升的能見度。

On the commercial side, we have established coverage in both community and academic hematology, key account capabilities, and market access expertise. And through KaryoForward, we have an existing patient support platform designed to help patients and caregivers navigate access, reimbursement, and treatment initiation. Importantly, these capabilities already work together today in multiple myeloma and can now be leveraged to support the potential expansion of selinexor into myelofibrosis, which is a significant strategic advantage to enable a rapid and efficient launch.

在商業面，我們已在社區與學術血液腫瘤領域建立覆蓋、具備關鍵客戶（key account）能力，以及市場准入專業。此外，透過 KaryoForward，我們已有既有的病患支持平台，旨在協助病患與照護者處理用藥取得、給付/報銷與治療啟動等流程。重要的是，這些能力目前已在多發性骨髓瘤領域協同運作，並可用來支持 selinexor 潛在擴展至骨髓纖維化；這是一項重大的策略優勢，可促成快速且高效率的上市推進。

Turning to slide 26, Q2 was a breakout quarter with top-tier recognition across leading global oncology platforms. As Richard discussed, the SENTRY data have now been presented at ASCO and EHA, published in the Journal of Clinical Oncology, and continue to be discussed at scientific meetings throughout the hematology community.

請看第 26 張投影片，第二季是表現突出的季度，在全球主要腫瘤學平台獲得頂級認可。如 Richard 所述，SENTRY 數據已在 ASCO 與 EHA 發表、刊登於《Journal of Clinical Oncology》，並持續在血液學社群的各類科學會議中被討論。

Importantly, while commercial promotion begins only following regulatory approval, scientific engagement is already well underway. The Medical and Scientific Affairs Organization is already deeply engaged within the myelofibrosis community. Following ASCO and EHA, our medical and scientific affairs teams have continued scientific exchange with investigators and treating physicians, participated in regional educational programs and scientific symposia, and continued building upon the relationships established throughout the SENTRY clinical development program.

重要的是，雖然商業推廣僅會在取得監管核准後才開始，但科學互動已經全面展開。醫學與科學事務組織已在骨髓纖維化社群中深度投入。在 ASCO 與 EHA 之後，我們的醫學與科學事務團隊持續與研究者及治療醫師進行科學交流，參與區域教育計畫與科學研討會，並持續深化在 SENTRY 臨床開發計畫期間所建立的關係。

We see significant engagement and thoughtful discussion surrounding the SENTRY results, particularly the rapid, deep, and sustained spleen responses, the promising overall survival findings, and the potential for disease modification.

我們看到圍繞 SENTRY 結果有高度參與與深思熟慮的討論，尤其是快速、深度且持久的脾臟反應、令人鼓舞的整體存活（OS）發現，以及疾病修飾的潛力。

Furthermore, the structure of the myelofibrosis market is also well aligned with our existing footprint as shown on slide 27. Approximately 70% of patients are treated in the community setting and 30% in academic centers. Across both settings, the majority of patients are concentrated within a manageable group of treatment centers. This concentration allows us to focus our resources on the physicians caring for the majority of patients and to deploy our existing organization efficiently.

此外，如第 27 張投影片所示，骨髓纖維化市場的結構也與我們既有的佈局高度契合。約 70% 的患者在社區醫療場域接受治療，30% 在學術中心。在兩種場域中，多數患者集中於一個可管理的治療中心群。這種集中度使我們能將資源聚焦於照護大多數患者的醫師，並有效率地部署我們既有的組織。

Our physician segmentation work has also given us a detailed understanding of the high-volume, innovation-oriented physicians most likely to adopt a new combination approach early. These physicians place significant importance on achieving rapid, deep, and sustained spleen responses and are actively considering how treatment may influence longer-term outcomes.

我們對醫師分群（segmentation）的工作也讓我們更細緻地了解：哪些高量、重視創新的醫師最可能在早期採用新的聯合治療策略。這些醫師非常重視達成快速、深度且持久的脾臟反應，並正積極思考治療如何影響較長期的結果。

There is also opportunity for prevalent patients treated with a JAK inhibitor to benefit from the combination therapy. We hear physician interest in the ability of selinexor to maintain spleen responses even when ruxolitinib doses are reduced, which is clinically relevant given how frequently dose adjustments occur in practice.

此外，對於目前正在使用 JAK 抑制劑治療的既有患者（prevalent patients），也存在從聯合療法中受益的機會。我們聽到醫師對 selinexor 在降低 ruxolitinib 劑量時仍能維持脾臟反應的能力感到興趣；鑑於臨床實務中劑量調整相當常見，這具有臨床相關性。

Finally, as we turn to slide 28 and looking at the commercial opportunity in myelofibrosis, we believe selinexor plus ruxolitinib has the potential to generate up to approximately $1 billion in peak annual revenue in the US alone. Approximately 20,000 patients are currently living with myelofibrosis in the US with roughly 4,000 newly treated frontline patients each year with no approved combination therapy in frontline myelofibrosis.

最後，請看第 28 張投影片，談到骨髓纖維化的商業機會，我們相信 selinexor 加上 ruxolitinib 在美國單一市場的年峰值營收潛力可達約 10 億美元。目前美國約有 20,000 名骨髓纖維化患者，每年約有 4,000 名新接受一線治療的患者，而在一線骨髓纖維化治療中尚無已核准的聯合療法。

Let's now review our multiple myeloma performance, which continues to provide the commercial and operational foundation for the broader hematology platform I have described. As shown on slide 30, we delivered another quarter of strong commercial execution with XPOVIO U.S. net product revenue of $30.8 million. Underlying demand remained relatively consistent with the second quarter of last year, despite an increasingly competitive treatment landscape.

接下來我們回顧多發性骨髓瘤的表現；這仍持續為我所描述的更廣泛血液腫瘤平台提供商業與營運基礎。如第 30 張投影片所示，我們在本季再次展現強勁的商業執行力，XPOVIO 美國淨產品營收為 3,080 萬美元。儘管治療競爭態勢日益激烈，基礎需求仍與去年第二季大致一致。

This performance reflects the resilience of our multiple myeloma franchise and importantly, the strength of the relationships our commercial organization has built with hematologists and oncologists across both community and academic practices.

此表現反映了我們多發性骨髓瘤產品線的韌性；更重要的是，也反映出我們商業團隊在社區與學術醫療場域的血液科與腫瘤科醫師之間所建立關係的強度。

Turning to slide 31, we continue to believe XPOVIO is well positioned for sustained performance. Our focus remains on the community setting, which represents approximately 60% of our US business, where physicians continue to value XPOVIO as a differentiated and convenient oral therapy.

請看第 31 張投影片，我們仍相信 XPOVIO 具備持續穩健表現的良好定位。我們的重點仍放在社區醫療場域，該場域約占我們美國業務的 60%；在此，醫師持續將 XPOVIO 視為具差異化且便利的口服治療選項。

In addition, XPOVIO continues to occupy a unique position in the evolving treatment landscape surrounding T-cell engaging therapies, providing physicians with flexibility both before a CAR-T therapy and following progression on a T-cell engaging therapy. Our commercialization capabilities position us to continue to build on the foundation of multiple myeloma and, importantly, drive a transformative launch in the multi-billion dollar myelofibrosis marketplace.

此外，在圍繞 T 細胞接合（T-cell engaging）療法的治療版圖持續演進之際，XPOVIO 仍占有獨特位置，讓醫師在 CAR-T 治療之前，以及在 T 細胞接合療法進展後，都能保有治療彈性。我們的商業化能力使我們能持續在多發性骨髓瘤的基礎上再接再厲，並且重要的是，在數十億美元規模的骨髓纖維化市場推動具變革性的上市。

With that, I'll turn the call over to Lori to review our financial results and discuss how our disciplined capital allocation strategy supports the opportunities ahead.

接下來，我把電話會議交給 Lori，請她回顧我們的財務結果，並說明我們嚴謹的資本配置策略如何支持 Richard 所概述的未來機會。

Thank you, Sohanya, and good morning, everyone. Turning to slide 33, I will focus on our second quarter financial performance, our financial outlook, and the actions we're taking to support the important milestones Richard outlined. Starting with revenue, total revenue for the second quarter was $33.4 million compared to $37.9 million in the prior year period.

謝謝你，Sohanya，各位早安。請看第 33 張投影片，我將聚焦於我們第二季的財務表現、財務展望，以及我們為支持 Richard 所提出的重要里程碑而採取的行動。先從營收開始，第二季總營收為 3,340 萬美元，較去年同期的 3,790 萬美元下降。

The reimbursement of development-related expenses at the end of 2025, which reduced revenue by approximately $6.5 million compared with the prior year quarter. US XPOVIO net product revenue was $30.8 million compared to $29.7 million in the prior year period. Underlying demand remained consistent, and our gross to net rate of 26.6% was comparable to the second quarter of 2025.

於2025年底就開發相關費用進行的補償，使營收較去年同期季度約減少650萬美元。美國XPOVIO淨產品營收為3,080萬美元，較去年同期的2,970萬美元增加。基本需求維持一致，我們26.6%的毛到淨（gross-to-net）比率與2025年第二季相當。

Turning to expenses, we remain focused on disciplined execution. R&D expenses were $29 million and SG&A expenses were $25.9 million, down 12% and 9% respectively year over year. This reflects our continued prioritization, disciplined investment, and focus on advancing our highest value late-stage programs with our Phase 3 trials having completed enrollment.

談到費用方面，我們仍專注於嚴謹執行。研發（R&D）費用為2,900萬美元，銷售、一般及行政（SG&A）費用為2,590萬美元，分別較去年同期下降12%與9%。這反映我們持續的優先排序、紀律性投資，以及聚焦推進最高價值的後期項目，且我們的第3期試驗已完成收案。

We also continue to maintain disciplined alignment of prelaunch investments with clinical and regulatory milestones. Net loss was $67 million for the quarter, compared to $37.3 million in the prior year period. As a reminder, net loss includes non-cash mark-to-market adjustments related to our financing structure. From an underlying operating perspective, performance improved with approximately an 8% reduction in loss from operations, reflecting stable net product revenue and continued expense discipline. Turning to the balance sheet, we ended the quarter with $65.4 million in cash, cash equivalents, restricted cash, and investments.

我們也持續以紀律性方式，使上市前投資與臨床及法規里程碑保持一致。本季淨損為6,700萬美元，去年同期為3,730萬美元。提醒一下，淨損包含與我們融資結構相關的非現金按市價評價（mark-to-market）調整。從基本營運角度來看，營運表現有所改善，營業損失約減少8%，反映淨產品營收穩定以及持續的費用紀律。就資產負債表而言，本季末我們持有現金、約當現金、受限制現金及投資合計6,540萬美元。

Based on our current operating plan, we expect our existing liquidity, including cash, cash equivalents, and investments, together with anticipated cash flow from net product revenue and license and other revenue, to fund our current operating plans into September 2026. On September 10, 2026, a $15.8 million principal payment is due under our Senior Secured Term Loan Facility. If that payment is made without additional financing or a waiver from our lenders, we expect our cash, cash equivalents, and investments will fall below our $10 million minimum liquidity covenant, which would constitute an event of default under the term loan. Importantly, our immediate priority is to address this and strengthen our financial position and provide the flexibility needed to continue executing our myelofibrosis strategy. Every capital allocation decision we make is intended to support the important clinical, regulatory, and commercial milestones ahead while maintaining disciplined execution across our multiple myeloma business and maximizing long-term value for patients and shareholders.

根據我們目前的營運計畫，我們預期現有流動性（包括現金、約當現金及投資），加上預期來自淨產品營收以及授權與其他收入的現金流，將可支應我們目前的營運計畫至2026年9月。依據我們的優先擔保定期貸款融資（Senior Secured Term Loan Facility），2026年9月10日將到期支付1,580萬美元的本金。若在未取得額外融資或未獲貸方豁免的情況下支付該款項，我們預期現金、約當現金及投資將低於1,000萬美元的最低流動性財務契約（covenant），這將構成該定期貸款項下的違約事件。重要的是，我們當前的首要任務是處理此事、強化財務狀況，並提供持續執行我們骨髓纖維化策略所需的彈性。我們所做的每一項資本配置決策，皆旨在支持未來重要的臨床、法規與商業里程碑，同時在多發性骨髓瘤業務上維持紀律性執行，並為病患與股東最大化長期價值。

Turning to guidance, we are reaffirming our full year 2026 outlook. We continue to expect total revenue in the range of $130 million to $150 million. It's license and other revenue consisting entirely of royalties over the next 2 quarters and U.S. XPOVIO net product revenue of $115 million to $130 million. We continue to expect combined R&D and SG&A expenses of $230 million to $245 million in 2026, excluding certain one-time costs that we may incur associated with our endometrial cancer program and evaluating financing opportunities and or strategic transactions.

談到財測指引，我們重申2026年全年展望。我們仍預期總營收將介於1.30億至1.50億美元。其中，授權與其他收入在未來2個季度將完全由權利金構成；美國XPOVIO淨產品營收預期為1.15億至1.30億美元。我們仍預期2026年研發與SG&A合計費用為2.30億至2.45億美元，不包含我們可能因子宮內膜癌計畫以及評估融資機會和/或策略交易而產生的某些一次性成本。

As a result of our decision to prioritize myelofibrosis and multiple myeloma, we are actively reducing investment across the endometrial cancer program, and we expect our cost structure to decline over time. A greater financial benefit will be realized in 2027 as we continue patient follow-up for the near-term and evaluate the evolving data set together with responsibly completing the remaining clinical and operational activities associated with the XPORT-EC-042 trial. In the near term, third quarter expenses may be modestly higher than the second quarter. This reflects a unique transition period for the company as we simultaneously advance our myelofibrosis program, implement the organizational changes associated with our decision to prioritize myelofibrosis and multiple myeloma following the XPORT-EC-042 top line results, and the costs we may incur to evaluate financing opportunities and strategic alternatives. With that, I will turn the call back over to Richard.

由於我們決定優先推進骨髓纖維化與多發性骨髓瘤，我們正積極降低在子宮內膜癌計畫上的投資，並預期我們的成本結構將隨時間下降。隨著我們在短期內持續進行病患追蹤、評估不斷演進的資料集，並負責任地完成與XPORT-EC-042試驗相關的其餘臨床與營運活動，較大的財務效益將在2027年顯現。短期內，第三季費用可能會略高於第二季。這反映公司正處於一段獨特的轉換期：我們同時推進骨髓纖維化計畫、在XPORT-EC-042主要結果公布後落實因優先骨髓纖維化與多發性骨髓瘤決策所帶來的組織調整，以及我們可能為評估融資機會與策略替代方案而產生的成本。接下來，我把電話交回給Richard。

Thank you.

謝謝。

Before we open the call for questions, I'd like to leave you with 1 final thought. Karyopharm is entering 1 of the most important periods in our history. We have a compelling opportunity in myelofibrosis, a regulatory path forward, an experienced hematology organization prepared to support a potential launch, if approved, and a team that has consistently demonstrated the ability to execute with focus, urgency, and discipline. We also recognize the importance and urgency of this moment, and that is why we are acting with discipline, not only in advancing our myelofibrosis program, but also in how we allocate capital and evaluate the financing opportunities and strategic alternatives discussed today. Every decision we make is guided by a single objective, maximizing long-term value for patients and shareholders.

在我們開放提問之前，我想留給各位最後一個想法。Karyopharm正進入我們歷史上最重要的時期之一。我們在骨髓纖維化領域擁有極具吸引力的機會、明確的法規推進路徑、一個有經驗的血液腫瘤團隊已準備好在獲批後支持潛在上市，以及一支持續展現能以專注、緊迫感與紀律執行的團隊。我們也認知到此刻的重要性與急迫性，因此我們以紀律行事，不僅在推進骨髓纖維化計畫上如此，也體現在我們如何配置資本，以及如何評估今天所討論的融資機會與策略替代方案。我們所做的每一項決策都以單一目標為指引：為病患與股東最大化長期價值。

I'd like to thank our employees for their extraordinary dedication, our investigators and collaborators for their partnership, and most importantly, the patients and families who have placed their trust in Karyopharm by participating in our clinical trials. We appreciate your continued support and look forward to updating you on our progress over the coming quarters. And with that, operator, we'd now be pleased to take your questions. Thank you.

我要感謝我們員工非凡的投入，感謝研究者與合作夥伴的協作，更重要的是，感謝參與我們臨床試驗、將信任託付給Karyopharm的病患與家屬。我們感謝各位持續的支持，並期待在未來幾個季度向各位更新我們的進展。那麼，接線員，我們現在很樂意回答各位的問題。謝謝。

(Operator Instructions)

（接線員指示）

Edward Tenthoff, Piper Sandler.

Edward Tenthoff，Piper Sandler。

I just had some questions with respect to what still had to be done for the sBLA or sNDA, considering obviously that selinexor is already approved in multiple myeloma. You know, how much of the filing is already done and is there anything you'll say you need to compile on the clinical side, any sites that need to be revisited, or does all that already seem to be taken care of with the current approval?

我有一些問題，關於sBLA或sNDA仍需要完成哪些工作；考量到selinexor顯然已在多發性骨髓瘤獲得核准。你知道，申請文件已完成多少？在臨床端是否還有需要彙整的內容、是否有任何試驗中心需要重新查核，或是因為目前的核准狀態，這些看起來都已經處理好了？

Thank you, Ted. I'll turn to Reshma to go into that in more detail.

謝謝你，Ted。我請Reshma更詳細說明。

Yes, thank you, Ted and Richard. So Ted, the team has actively been working on the sNDA, by and large, the vast majority has already been put together. It's ready to go. 1 of the key pieces that we are just aligning and finalizing with the FDA is just around the confirmatory data piece, right? So I think as we all appreciate under accelerated approval, we are provided an approval, a label, but we do need to provide clinical benefit at some point in the future.

是的，謝謝你，Ted和Richard。Ted，團隊一直在積極準備sNDA；整體而言，絕大多數內容都已經整理完成。已經準備就緒。我们目前正與FDA對齊並完成定稿的其中一個關鍵部分，是關於確認性數據（confirmatory data）的部分，對吧？我想大家都理解，在加速核准（accelerated approval）之下，我們會獲得核准與標籤，但在未來某個時間點仍需要提供臨床效益的證據。

And so right now our discussions really have been focused on using the mature overall survival observed from SENTRY. We're finalizing the statistical analysis plans, again, aligning on those last details, which is something that is required before we submit the sNDA. So great productive conversations with the FDA, and we still are very much on track to submit the sNDA in August.

因此，目前我們的討論確實一直聚焦於使用 SENTRY 觀察到的成熟整體存活期（OS）資料。我們正在敲定統計分析計畫，再次就最後細節達成一致，這是在我們提交 sNDA 之前所必需的。因此，與 FDA 的對話非常順利且富有成效，我們仍然非常按計畫在 8 月提交 sNDA。

That's really helpful. Just to make sure I understand, so you'll use the OS data from the ongoing SENTRY as the confirmatory data set?

這非常有幫助。只是確認我理解正確：你們會使用正在進行中的 SENTRY 的 OS 資料作為確認性資料集嗎？

That is correct. We designed SENTRY intentionally from the very beginning to follow all the way for overall survival so that study continues with patients' sites blinded. They continue on treatment. They continue to provide scans as well as OS data. So yes, we are going to leverage that maturing OS to confirm the benefit, which is going to occur likely years from now, but that is going to serve as the confirmatory data set.

沒錯。我們從一開始就有意將 SENTRY 設計為一路追蹤至整體存活期，因此該研究會在病患研究中心維持盲態的情況下持續進行。他們會持續接受治療。他們也會持續提供影像掃描以及 OS 資料。所以是的，我們將利用這些逐漸成熟的 OS 來確認療效；這很可能要在多年之後才會發生，但它將作為確認性資料集。

We believe, you know, upon alignment with the FDA.

我們相信，在與 FDA 達成一致之後。

That's really helpful. Thanks, Reshma. Well, good luck.

這非常有幫助。謝謝你，Reshma。那麼，祝你好運。

Yanni Souroutzidis, Cantor.

Yanni Souroutzidis，Cantor。

I guess just a quick question on kind of what is the right way to think about the feasibility here of future operations. Is accelerated approval absolutely needed, or do you believe that inclusion in the NCCN committee could provide sufficient revenues to address the debt and operating needs? And I have a quick follow-up.

我想快速問一下，關於未來營運可行性應該如何看待。加速核准是否絕對必要？或者你們認為納入 NCCN 委員會是否能帶來足夠的收入，以應付債務與營運需求？我還有一個簡短的追問。

Yes, thanks, Yanni. You know, I think as we've talked to, there's really, you know, a few of those milestones happening very much in the near term. And obviously, given that we're already an approved agent, you know, NCCN is very important, and I think it's something which, as we know, physicians utilize a lot. I think we've talked to that previously where, you know, with NCCN in similar situations, if NCCN is all that you achieve, usually products will achieve about 50% of what their peak may be. But obviously, our goal is to enable as broad access as possible.

是的，謝謝你，Yanni。你知道，我想如同我們談到的，近期確實會有幾個里程碑很快發生。而且顯然，鑑於我們已經是一個獲核准的藥物，NCCN 非常重要，我也認為這是我們所知醫師非常常用的工具。我想我們之前也談過，在類似情況下，如果你能達成的只有 NCCN，通常產品大約能達到其峰值的 50%。但顯然，我們的目標是讓病患能夠獲得盡可能廣泛的使用機會。

1 component is NCCN. The other component, as we've talked to, is really continuing to advance down the regulatory pathway. So, you know, I think both of those are occurring very, very positively over the near term. And I think both would be very positive for us in terms of, you know, being able to fund operations and obviously being able to enable patients to get access to selinexor and ruxolitinib in myelofibrosis.

其中一個組成部分是 NCCN。另一個組成部分，如同我們談到的，是持續沿著法規途徑推進。所以，我認為這兩者在近期都進展得非常、非常正面。而且我認為，這兩者對我們而言都會非常正面，因為能讓我們有能力支應營運資金，並且顯然能讓骨髓纖維化病患取得 selinexor 與 ruxolitinib 的治療。

Yes, appreciate it. And then just, I guess, relatedly to, you know, appreciate the transparency on kind of the upcoming payment required and the debt covenants there. I guess, is there a sense of what would be kind of the stopgap in your mind to kind of position the company well financially from a liquidity perspective to make it through these near-term milestones? And, you know, ideally, I would imagine make it through at least the first half or end of 2027.

是的，感謝。另外，我想也相關地說，謝謝你們對即將到期的付款需求以及相關債務契約條款的透明說明。我想問的是：從流動性角度來看，你們心目中是否有一個「權宜之計」，能讓公司在財務上處於良好位置，以度過這些近期里程碑？並且理想情況下，我想像至少能撐到 2027 年上半年或年底。

Yes, I think, you know, as we've seen before, our lenders have consistently been very, very supportive with us and I don't have any reason to believe that they won't continue to do so. And so I think as we announced, we are working on a range of financing opportunities and strategic alternatives. We're in direct dialogue with our lenders with respect to these options.

是的，我想如同我們之前所見，我們的放款人一直以來都非常、非常支持我們，我沒有理由相信他們不會繼續如此。因此，如同我們所公告的，我們正在評估一系列融資機會與策略性替代方案。我們也正就這些選項與放款人直接對話。

And I think obviously our goal is to work with lenders and potential equity investors and find a way to, you know, enhance our liquidity, extend the runway as we have these really important milestones, you know, in front of us in the second half of 2026. So I think, you know, we'll be able to continue to execute on that and find the right balance as we move forward.

而且我想，顯然我們的目標是與放款人及潛在股權投資人合作，找到方法來提升我們的流動性、延長資金可支撐的期間，因為在 2026 年下半年我們面前有這些非常重要的里程碑。所以我想，我們將能持續推進執行，並在往前走的過程中找到適當的平衡。

Brian Abrahams, RBC Capital Markets.

Brian Abrahams，RBC Capital Markets。

You mentioned in milestones the potential for inclusion of selinexor in the compendia in the back half of this year. That seems pretty rapid if the NCCN meeting is happening just this week. So I'm just curious if you're hearing anything emerging from the meeting that gives you confidence and maybe you could remind us of the process there. And then maybe just secondly, just curious if in your dialogue you're hearing any insights from the FDA on whether, and how open they might be to priority review.

你們在里程碑中提到，今年下半年 selinexor 可能被納入彙編（compendia）。如果 NCCN 會議就在本週舉行，這看起來相當快。所以我想了解，你們是否從會議中聽到任何正在浮現的訊息，讓你們更有信心？也許你們可以再提醒我們那邊的流程。另外第二點，我也好奇在你們的對話中，是否從 FDA 那裡聽到任何洞見：他們是否、以及在多大程度上，可能願意給予優先審查（priority review）。

Sure, thanks, Brian. I'll address the first part and I'll turn to Reshma for the second part. You know, obviously, you know, NCCN is an independent committee and an independent body. So, you know, they'll go through their process and evaluate. Importantly, we've put the right components in place in terms of our, you know, ASCO presentation, our EHA presentation, our Journal of Clinical Oncology manuscripts.

好的，謝謝，Brian。我先回答第一部分，第二部分我交給 Reshma。你知道，顯然 NCCN 是一個獨立委員會與獨立機構。所以他們會依照其流程進行並做出評估。重要的是，我們已在我們的 ASCO 發表、EHA 發表，以及《Journal of Clinical Oncology》的論文稿件方面，備妥了正確的組成要素。

I think all the right components are there, and we hear a high level of interest from opinion leaders to be able to get access to selinexor plus ruxolitinib. I think we're on track, as we said, to see that in the second half this year. I'll turn to Reshma to talk to the FDA.

我認為所有正確的要素都已到位，而且我們也聽到意見領袖對於能取得 selinexor 加 ruxolitinib 的高度興趣。如同我們所說，我們仍按計畫在今年下半年看到那項進展。我把時間交給 Reshma 來談 FDA。

Yes, thanks, Brian. You know, so as I mentioned, you know, really great productive conversations with the FDA. In terms of priority review, not necessarily. So this is, you know, a request that we need to make with the FDA at the time that the application is submitted. They have approximately 60 days to review that request, and then they'll provide that update shortly thereafter.

是的，謝謝，Brian。如我提到的，我們與 FDA 的對話非常順利且富有成效。就優先審查而言，目前不一定。這是我們在提交申請時需要向 FDA 提出的請求。他們大約有 60 天時間審查該請求，之後不久就會提供更新。

So no specific insight, but we do believe that we have a strong package, potentially a differentiating profile, a need for a combination therapy. So hopefully they will review it and expedite the PDUFA date that will enable an approval sometime early next year.

因此沒有特定的洞見，但我們確實相信我們的資料包很強，可能具有差異化特徵，也存在對聯合療法的需求。所以希望他們會審查並加速 PDUFA 日期，讓我們能在明年年初某個時間獲得核准。

Maury Raycroft, Jefferies.

Maury Raycroft，Jefferies。

Maybe I'll just ask one on the term loan negotiations. Lori, you mentioned potential for a waiver. What do those discussions look like and what could updated obligations look like if there's a waiver and what is the likelihood of that? Then I've got a follow-up question.

我想我先問一個關於定期貸款協商的問題。Lori，你提到可能會有豁免。這些討論目前看起來是什麼樣子？如果有豁免，更新後的義務可能會是什麼樣子？以及其可能性有多大？然後我還有一個追問。

Sure. Maybe, Maury, I'll address that one. I mean, just at a high level, we're not going to obviously go into the details of the conversations and negotiations. But I think, as we mentioned, the lenders have been consistently supportive with us. And again, I think we don't have any reason to believe that they won't continue to do so.

好的。Maury，這題或許我來回答。我的意思是，從高層次來看，我們顯然不會深入談話與協商的細節。但我認為，如同我們提到的，貸方一直以來都持續支持我們。而且同樣地，我們沒有任何理由相信他們不會繼續這麼做。

So, good, productive conversations and working on the right solution as we move forward. And obviously, that's something that we're very focused on and working to achieve rapidly.

所以，這些對話是良好且具建設性的，我們也在往前推進、尋找正確的解決方案。而且很明顯，這是我們非常專注並努力要迅速達成的事情。

Understood. That's helpful. And then for NCCN compendial listing, I guess, what's your plan to get patients from your clinical studies on the paid drug? And do you have a sense of proportion of patients from your studies that would make that switch early on with only the NCCN compendial listing?

了解。這很有幫助。另外，關於 NCCN 彙編（compendial）收錄，我想問你們的計畫是什麼，如何讓臨床研究中的病人轉用付費藥物？以及在只有 NCCN 彙編收錄的情況下，你們是否掌握研究中病人會在早期就轉換的比例？

Sure. Well, I think on our study, as we mentioned, we look to see our study continue, right? So our study continues. Patients are blinded. Clinicians are blinded.

好的。我想就我們的研究而言，如同我們提到的，我們希望研究能持續進行，對吧？所以我們的研究會持續。病人是盲態。臨床醫師也是盲態。

We have a blinded study team inside Karyopharm. So we would look to see our study continue. And I think, as Reshma mentioned, we're looking to see that to be the confirmatory data from an accelerated approval perspective. So our focus would be to make sure we're really working with the sites, investigators, patients, et cetera, to continue patients on our Phase 3 program.

我們在 Karyopharm 內部也有一個盲態的研究團隊。因此我們會希望研究持續進行。而且我認為，如 Reshma 所提到的，我們希望這能作為加速核准角度下的確認性數據。所以我們的重點會是確保我們確實與各研究中心、研究者、病人等密切合作，讓病人持續留在我們的第三期計畫中。

Michael King, Rodman & Renshaw.

Michael King，Rodman & Renshaw。

Just a little further granularity on the filing and the interaction with the FDA. I just wondering, given the recent interaction with the Type B and C meetings and the updated analysis that you presented at ESMO, I just wonder if any part of the data set that you're going to submit could be considered to be a major amendment. Obviously, this would be very impactful for the approval timeline. So I'm just wondering how you're thinking about submitting the data to the agency.

我想再更細一點問一下申請送件以及與 FDA 的互動。我在想，考量近期與 Type B 與 Type C 會議的互動，以及你們在 ESMO 發表的更新分析，我想知道你們將提交的資料集中，是否有任何部分可能被視為重大修訂（major amendment）。顯然這會對核准時程造成很大影響。所以我想了解你們打算如何向主管機關提交這些資料。

Yes, let me turn to Reshma for that part.

是的，這部分我請 Reshma 來回答。

Yes, thanks, Michael. Great question. So the sNDA, you know, under the accelerated approval is really going to be based upon the week 24 data. So the week 24 that we really believe is compelling and differentiating, of course, is going to be that SVR35 data. Not only at week 24, that's the time point at which the primary analysis was conducted, but the kinetics really suggest something very differentiating.

是的，謝謝你，Michael。這是個很好的問題。所以 sNDA，你知道，在加速核准之下，主要會以第 24 週的數據為基礎。我們確實相信第 24 週的數據非常有說服力且具差異化，當然就是 SVR35 的數據。不僅是在第 24 週（那是進行主要分析的時間點），其動態變化（kinetics）也確實顯示出非常差異化的特徵。

So, of course, that SVR35 at week 12, 24, 36 shows that sustained SVR, of course, the overall survival data, the post hoc analysis with the relationship between SVR35, OS, the disease modification data and the safety. So that's the profile, again, very compelling at week 24. And again, we'll form the basis for that for the sNDA.

所以，當然，第 12、24、36 週的 SVR35 顯示了持續性的 SVR；當然也包括整體存活（OS）數據、SVR35 與 OS 關係的事後分析（post hoc analysis）、疾病修飾（disease modification）數據以及安全性。所以這個整體輪廓在第 24 週時再次顯得非常有說服力。而且同樣地，這將構成 sNDA 的基礎。

Okay, and no 48-week data to be submitted then, is that correct?

好的，那麼就不會提交 48 週的數據了，對嗎？

That's correct. We're going to really focus on the week 24 data. Now, there are some patients that have been followed for week 48. You know, we'll provide that data as well, but, you know, the primary focus is really going to be on the week 24.

沒錯。我們會真正聚焦在第 24 週的數據。當然，有些病人已追蹤到第 48 週。我們也會提供那些數據，但主要重點確實會放在第 24 週。

Okay, and can you say whether you'll include the pre-specified OS confirmatory analysis in that submission?

好的，那你能否說明你們是否會在這次提交中納入預先指定的 OS 確認性分析？

Yes, absolutely. That's part of the differentiating package. And that OS data that we observed and, of course, presented at ASCO, EHA, and was included in the JCO really was the basis for that post-hoc analysis that allowed us to show that relationship between SVR35, OS. So it is a very important data point. Of course, we'll continue to follow patients on overall survival. And as mentioned earlier, we'll use those data to ultimately confirm the benefit in the future.

是的，當然會。那是差異化資料包的一部分。而我們觀察到的 OS 數據，並且當然已在 ASCO、EHA 發表，也收錄於 JCO，確實就是該事後分析的基礎，使我們能夠顯示 SVR35 與 OS 之間的關係。所以這是一個非常重要的數據點。當然，我們會持續追蹤病人的整體存活。並且如先前所提，我們最終會使用這些數據在未來確認其效益。

Thank you, Michael. There are no additional questions in the queue. I will turn it back to Richard for some closing remarks.

謝謝你，Michael。目前佇列中沒有其他問題。我將把電話交回 Richard 做結語。

Thank you, Operator, and thank you everyone for joining us today and your continued interest in Karyopharm. I guess we've highlighted, you know, we very much look forward to providing you additional updates on our regulatory and financing developments very much in the near future. So, once again, thanks for joining us.

謝謝你，接線員，也謝謝各位今天加入我們，並持續關注 Karyopharm。我想我們已經強調過，我們非常期待在不久的將來，向各位提供更多關於我們法規與融資進展的更新。所以，再次感謝各位的參與。

Ladies and gentlemen, this concludes your conference call for today. Thank you for participating. You may now disconnect. Have a great day.

各位女士、先生，今天的電話會議到此結束。感謝各位參與。您現在可以掛線。祝您有美好的一天。