Karyopharm Therapeutics Inc (KPTI) 2023 Q1 法說會逐字稿

Good morning. My name is Ryan, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics First Quarter 2023 Financial Results Conference Call. (Operator Instructions) Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Elhan Webb, Senior Vice President, Investor Relations. Thank you. Over to you.

早上好。我叫 Ryan，今天我將擔任你們的會議操作員。此時，我歡迎大家參加 Karyopharm Therapeutics 2023 年第一季度財務業績電話會議。 （操作員說明）請注意，本次通話是應公司要求進行錄音的。我現在想將電話轉給投資者關係高級副總裁 Elhan Webb。謝謝。交給你了。

Thank you, operator, and thank you all for joining us on today's conference call to discuss Karyopharm's First Quarter 2023 financial results and recent company progress. We issued a press release this morning detailing our financial results for the first quarter 2023. This release, along with a slide presentation that we will reference during our call today are available on our website. For today's call, as seen on Slide 2, I'm joined by Richard, Sohanya, Reshma and Mike, who will provide an update on our Q1 results and recent clinical developments. 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.

感謝運營商，感謝大家參加今天的電話會議，討論 Karyopharm 2023 年第一季度的財務業績和公司最近的進展。我們今天早上發布了一份新聞稿，詳細介紹了 2023 年第一季度的財務業績。該新聞稿以及我們將在今天的電話會議中參考的幻燈片演示文稿可在我們的網站上獲取。正如幻燈片 2 所示，Richard、Sohanya、Reshma 和 Mike 也參加了今天的電話會議，他們將提供有關我們第一季度結果和近期臨床進展的最新信息。在我們開始正式評論之前，我要提醒您，我們今天發表的各種評論均構成前瞻性陳述，旨在實現 1995 年《私人證券訴訟改革法案》中安全港條款的目的，如幻燈片 3 所示。

Actual results may differ materially from those indicated by these forward-looking statements, FLS as a result of various important factors, including those discussed in the Risk Factors section of our most recent Form 10-K, which is on file with the SEC and in other filings that we may make with the SEC in the future.

由於各種重要因素，包括我們最新的 10-K 表格的風險因素部分中討論的因素，實際結果可能與這些前瞻性陳述、FLS 所示的結果存在重大差異，該表格已向 SEC 備案，並在我們將來可能向 SEC 提交的其他文件。

Any FLS represent RV as of today only. While we may elect to update this FLS at some point in the future, we specifically disclaim any opportunity to do so even if our views change. Therefore, you should not rely on these FLS as representing our views as of any later date. I will now turn the call over to Richard. Please turn to Slide 4.

截至今天，任何 FLS 均代表 RV。雖然我們可能會選擇在未來某個時候更新此 FLS，但我們特別聲明，即使我們的觀點發生變化，我們也不會有任何這樣做的機會。因此，您不應依賴這些 FLS 來代表我們以後的觀點。我現在將把電話轉給理查德。請翻到幻燈片 4。

Thank you, Elhan, and thank you all for joining us today for Karyopharm's Q1 2023 Earnings Call. As we turn to Slide 5, we are making strong progress as we execute on Karyopharm's next stage of growth by deploying our novel mechanism of action, selective inhibition of nuclear export, to expand our existing multiple myeloma franchise, currently centered around our commercial drug, XPOVIO, which is now approved in over 40 countries and continues to move into earlier lines of therapy in multiple myeloma.

謝謝 Elhan，也感謝大家今天參加 Karyopharm 的 2023 年第一季度收益電話會議。當我們轉向幻燈片 5 時，我們正在取得強勁進展，因為我們通過部署我們的新穎作用機制（選擇性抑制核輸出）來執行 Karyopharm 的下一階段增長，以擴大我們現有的多發性骨髓瘤特許經營權，目前以我們的商業藥物為中心， XPOVIO 現已在 40 多個國家獲得批准，並繼續進入多發性骨髓瘤的早期治療領域。

As Sohanya will discuss further, year-over-year, total demand for XPOVIO continues to grow. However, this is not translating into growth in net product revenue due to increased distribution of free product through our carryforward patient assistance program, PAP and higher gross-to-net discounts. These factors have caused us to revise our total revenue guidance for 2023 to a new range of $145 to $160 million.

正如 Sohanya 將進一步討論的那樣，XPOVIO 的總需求逐年持續增長。然而，這並沒有轉化為淨產品收入的增長，因為通過我們的結轉患者援助計劃、PAP 和更高的毛淨折扣增加了免費產品的分配。這些因素促使我們將 2023 年總收入指引修改為 145 至 1.6 億美元的新範圍。

In addition, we have accelerated our closure of nonpriority programs, thus lowering our spend in 2023 and we are maintaining our guidance for cash runway through late 2025. We believe the factors resulting in the significant increased use of our PAP programs are expected to be mostly limited to 2023. And while we are not specifically commenting on our revenue expectations for 2024, we believe we will see a decreased impact of this challenge next year given the IRA-related Medicare Part D redesign. We have a focused pipeline and are rapidly advancing our mid- and late-stage clinical development programs that can help patients who suffer from cancers with high unmet need, demonstrate efficacy at lower doses with improved tolerability and where we believe we'll have the highest probability of success.

此外，我們還加快了非優先項目的關閉速度，從而降低了 2023 年的支出，並且我們將維持對現金跑道的指導直至 2025 年末。我們認為，導致 PAP 項目使用量大幅增加的因素預計主要是僅限於 2023 年。雖然我們沒有具體評論 2024 年的收入預期，但我們相信，鑑於 IRA 相關的 Medicare D 部分重新設計，明年這一挑戰的影響將會減弱。我們擁有專注的管道，並正在快速推進我們的中後期臨床開發項目，這些項目可以幫助患有高度未滿足需求的癌症患者，證明較低劑量的療效和改善的耐受性，並且我們相信我們將擁有最高的成功的概率。

We are conducting pivotal Phase III studies in both multiple myeloma and endometrial cancer with the third pivotal Phase III study of myelofibrosis, which we expect to start in the first half of 2023. Collectively, we believe we have the potential to achieve multiple product approvals over the next 2 to 4 years as we deliver our next phase of growth, leveraging our proven and established commercialization and mid- to late-stage development capabilities as we work to generate value for patients and shareholders.

我們正在針對多發性骨髓瘤和子宮內膜癌開展關鍵的 III 期研究，其中第三項關鍵的 III 期研究針對骨髓纖維化，預計將於 2023 年上半年啟動。總的來說，我們相信我們有潛力在超過 20 年的時間裡獲得多項產品批准。未來 2 到 4 年，我們將利用我們經過驗證和成熟的商業化以及中後期開發能力，實現下一階段的增長，努力為患者和股東創造價值。

As we look at our first quarter highlights on Slide 6, we achieved $28.3 million XPOVIO net product revenue for the quarter, which is consistent with the first quarter last year. Total demand for XPOVIO grew year-over-year in a very competitive multiple myeloma marketplace, and we are encouraged by the continued growth in the community setting. Shifting to selinexor's position internationally, our continued global expansion provides further opportunities to treat patients in need with the additions of new license territories with Menarini in the Middle East and Africa as well as full marketing authorization for an XPOVIO in the U.K., broadening our international footprint.

當我們在幻燈片 6 上查看第一季度亮點時，我們在該季度實現了 2830 萬美元的 XPOVIO 產品淨收入，這與去年第一季度一致。在競爭非常激烈的多發性骨髓瘤市場中，對 XPOVIO 的總需求逐年增長，我們對社區環境的持續增長感到鼓舞。轉向 selinexor 的國際地位，我們持續的全球擴張為治療有需要的患者提供了更多機會，與美納里尼在中東和非洲增加了新的許可區域，以及 XPOVIO 在英國的全面營銷授權，擴大了我們的國際足跡。

We continue to advance a streamlined clinical pipeline focused on our 4 core programs. I want to highlight our recent data presented at AACR in treatment-naive myelofibrosis, where selinexor 60 milligram in combination with ruxolitinib demonstrated rapid, deep and sustained spleen response.

我們繼續推進專注於我們的 4 個核心項目的精簡臨床管道。我想強調一下我們在 AACR 上公佈的關於未經治療的骨髓纖維化的最新數據，其中 60 毫克 selinexor 與魯索替尼聯合顯示出快速、深入和持續的脾臟反應。

Based on this, we are planning to initiate a pivotal Phase III study this quarter as we believe selinexor 60 milligram plus ruxolitinib has the potential to transform standard of care for frontline myelofibrosis. Additionally, earlier this week, we announced encouraging interim efficacy data from the Phase II study of eltanexor, our second novel sign compound in 30 patients with hard-to-treat higher-risk, relapsed or refractory MDS, which Reshma will discuss. With that, I would now like to turn the call over to Sohanya on Slide 7 for her review of the commercial performance for the quarter and perspectives on our updated guidance for 2023. Sohanya?

基於此，我們計劃在本季度啟動一項關鍵的 III 期研究，因為我們相信 selinexor 60 毫克加魯索替尼有潛力改變一線骨髓纖維化的護理標準。此外，本週早些時候，我們宣布了 eltanexor 的 II 期研究令人鼓舞的中期療效數據，eltanexor 是我們的第二個新標誌化合物，針對 30 名難以治療的高風險、復發或難治性 MDS 患者，Reshma 將對此進行討論。現在，我想將電話轉給幻燈片 7 上的 Sohanya，請她回顧本季度的商業業績以及對我們更新的 2023 年指引的看法。Sohanya？

Thank you, Richard, and good morning, everyone. On Slide 8, I will be discussing first quarter of XPOVIO performance within an evolving and competitive multiple myeloma landscape. In the first quarter, XPOVIO continued to show growth year-over-year in total demand and new patient starts despite facing a competitive landscape that intensified over the past year. Net product revenue was consistent with the same period last year and was adversely impacted by multiple external factors.

謝謝理查德，大家早上好。在幻燈片 8 上，我將討論 XPOVIO 第一季度在不斷發展和競爭激烈的多發性骨髓瘤領域的表現。儘管面臨過去一年加劇的競爭格局，但 XPOVIO 在第一季度的總需求和新患者啟動方面繼續呈現同比增長。產品淨收入與去年同期持平，但受到多種外部因素的不利影響。

When you look at what is positively driving our total demand, the community business continued to grow, contributing to about 70% of XPOVIO's revenues in the first quarter. In the community setting, XPOVIO continues to be viewed increasingly favorably as an effective, convenient oral and manageable therapy with a novel mechanism of action in second to fourth line. In the academic setting, we saw sustained demand year-over-year despite increasing uptake of the novel bispecifics and CAR-Ts.

當你看看是什麼積極推動了我們的總需求時，你會發現社區業務持續增長，貢獻了 XPOVIO 第一季度收入的約 70%。在社區環境中，XPOVIO 繼續被越來越多地視為一種有效、方便、易於管理的口服療法，在二線至四線具有新穎的作用機制。在學術環境中，儘管新型雙特異性藥物和 CAR-T 的採用不斷增加，但我們仍看到逐年持續的需求。

The positioning of XPOVIO is actively evolving in the academic setting with the emergence of T cell therapies, and we have an opportunity to serve key patient segments with an increasing body of evidence for XPOVIO that Reshma will expand upon shortly. Now let's take a look at some of the key headwinds we see that adversely impacted our net product revenues year-over-year.

隨著 T 細胞療法的出現，XPOVIO 的定位在學術環境中正在積極發展，我們有機會為關鍵患者群體提供服務，並提供越來越多的 XPOVIO 證據，Reshma 很快就會對此進行擴展。現在讓我們來看看我們看到的一些對我們的淨產品收入同比產生不利影響的主要阻力。

First, there was an impact from a higher gross to net discount, 5 points higher in Q1 2023 versus Q1 2022, driven by increased 340B discounts and Medicare and Medicaid rebates. Second, there was a significant increase in utilization of our carryforward patient assistance program, or PAP, where we provide free drug to patients who qualify and who are unable to afford the cost of their medication.

首先，受到 340B 折扣以及醫療保險和醫療補助回扣增加的推動，總折扣與淨折扣增加，2023 年第一季度比 2022 年第一季度高出 5 個百分點。其次，我們的結轉患者援助計劃（PAP）的利用率顯著增加，在該計劃中，我們向符合資格但無力承擔藥物費用的患者提供免費藥物。

Many patients rely on financial assistance from independent nonprofit foundation dedicated to improving access to important medications by providing financial support including programs supporting Medicare CAR-T patients who need co-pay assistance for their multiple myeloma oral therapy.

許多患者依賴獨立非營利基金會的經濟援助，該基金會致力於通過提供經濟支持來改善獲得重要藥物的機會，包括支持需要共同支付多發性骨髓瘤口服治療援助的 Medicare CAR-T 患者的計劃。

Medicare patients constitute about 60% of our total patient mix for XPOVIO. However, these foundations did not have sufficient funding and were unable to provide financial support to patients in Q1 of 2023 and continuing through the end of April. As a result, we faced an unprecedented increase in the use of our patient assistance program in this period.

醫療保險患者約佔 XPOVIO 患者總數的 60%。然而，這些基金會沒有足夠的資金，無法在 2023 年第一季度持續到 4 月底為患者提供財務支持。因此，在此期間，我們的患者援助計劃的使用量出現了前所未有的增長。

Historically, our PAP program attributed to approximately 5% of total demand and has steadily increased since February of this year, approaching 20% in April. Patients entering PAP remain in the program through the year and course of treatment. Thus, there is a cumulative effect over subsequent quarters due to the refills associated with these new starts. Now moving forward in 2024, IRA related changes in the design of Medicare Part D will eliminate the patient burden of the 5% beneficiary coinsurance requirement and we expect significantly less need for Medicare Part D patients to utilize carryforward for co-pay assistance.

從歷史上看，我們的 PAP 計劃約佔總需求的 5%，並且自今年 2 月以來穩步增長，4 月份接近 20%。進入 PAP 的患者在整個治療年和療程中仍保留在該計劃中。因此，由於與這些新啟動相關的補充，在隨後的季度中會產生累積效應。現在展望 2024 年，與 IRA 相關的 Medicare D 部分設計變化將消除患者 5% 受益人共同保險要求的負擔，我們預計 Medicare D 部分患者利用結轉來獲得共付援助的需求將大大減少。

While there are several external factors that can shift in the marketplace, the primary driver for revising our net product revenue guidance to $110 million to $125 million is higher year-to-date usage of PAP and their associated refill impact as well as our uncertainty around whether foundations supporting multiple myeloma patients will be able to provide financial support for new eligible patients throughout 2023.

雖然市場上存在一些可能發生變化的外部因素，但將我們的淨產品收入指導修改為 1.1 億美元至 1.25 億美元的主要驅動力是年初至今 PAP​​ 的使用量及其相關的補充影響以及我們對產品的不確定性。支持多發性骨髓瘤患者的基金會是否能夠在 2023 年為新的符合條件的患者提供財務支持。

We recognize the important role that XPOVIO can play in patients that are battling multiple myeloma, and we are dedicated to continuing to provide free access to XPOVIO for patients that qualify for our carryforward program. As we look to key drivers of growth for 2023 and beyond, we are pleased with the continued positive momentum across our leading indicators.

我們認識到 XPOVIO 在與多發性骨髓瘤作鬥爭的患者中可以發揮的重要作用，並且我們致力於繼續為符合我們結轉計劃資格的患者提供免費使用 XPOVIO 的機會。在我們展望 2023 年及以後增長的主要驅動力時，我們對領先指標持續保持積極勢頭感到高興。

Importantly, we continue to make strong progress in shifting into earlier lines. In Q1 2023, XPOVIO new patient share approached 60% in the second to fourth line compared to 45% in Q1 of last year. This is encouraging as it allows patients to potentially have a more optimal experience in the early lines and extend time on therapy. This is supported by our intent to prescribe data, which showed an improvement in tolerability perception in the second to fourth line.

重要的是，我們在轉向早期生產線方面繼續取得重大進展。 2023 年第一季度，XPOVIO 在第二至第四線的新患者份額接近 60%，而去年第一季度為 45%。這是令人鼓舞的，因為它可以讓患者在早期獲得更佳的體驗並延長治療時間。我們的處方數據意圖支持了這一點，數據顯示第二至第四線的耐受性感知有所改善。

Let's now turn to Slide 9. Amidst the crowded and evolving landscape, we believe we are strongly positioned as a novel class of therapy in the second to fourth line in between 3 major classes used in the first and second lines and T cell therapies in later lines. And I remain confident in our potential for mid- to long-term growth.

現在讓我們轉向幻燈片 9。在擁擠和不斷發展的環境中，我們相信我們在第一線和第二線使用的 3 個主要類別以及後來的 T 細胞療法之間作為第二到第四線的新型療法具有強大的定位。線。我對我們的中長期增長潛力仍然充滿信心。

We are positioning XPOVIO in 3 targeted patient populations. First, in the community setting where earlier line patients tend to be treated, XPOVIO is an optimal therapy in the second to fourth line post anti-CD38 treatments as a novel class of therapy that is an effective manageable, easily combinable and a convenient oral therapy. Second, as T-cell therapies emerge and are used increasingly in the academic setting, XPOVIO may be an optimal potentially T-cell bearing therapy that can be used at any stage of a patient's treatment journey. Reshma will expand upon the building body of evidence that suggests XPO1 inhibition may be associated with preserving T-cell health.

我們將 XPOVIO 定位於 3 個目標患者群體。首先，在早期一線患者傾向於接受治療的社區環境中，XPOVIO 是二線至四線抗 CD38 治療後的最佳療法，作為一種新型療法，是一種有效、易於管理、易於組合且方便的口服療法。其次，隨著 T 細胞療法的出現並在學術環境中越來越多地使用，XPOVIO 可能是一種最佳的潛在 T 細胞承載療法，可在患者治療過程的任何階段使用。 Reshma 將擴展大量證據，表明 XPO1 抑制可能與保持 T 細胞健康有關。

Finally, in the academic setting, a third segment of patients is the elderly patients that constitute about 2/3 of all of myeloma patients, and they typically are not able to access a T-cell therapy due to age and frailty. As we think about the mid- to long-term growth potential of XPOVIO in multiple myeloma, we're encouraged via XVd study, the triple combination of selinexor with pomalidomide and dexamethasone and find investment could lead to the only all oral potentially T cell sparing regimen in the marketplace, if approved.

最後，在學術界，第三部分患者是老年患者，約佔所有骨髓瘤患者的2/3，他們通常由於年齡和虛弱而無法獲得T細胞治療。當我們考慮 XPOVIO 在多發性骨髓瘤中的中長期增長潛力時，我們通過 XVd 研究（selinexor 與泊馬度胺和地塞米鬆的三重組合）受到鼓舞，並發現投資可能導致唯一的全口服潛在 T 細胞保留市場上的治療方案（如果獲得批准）。

Pomalidomide and IMiD has shown no potential negative impact on T cell function, unlike alkylating agents such as cyclophosphamide that have shown to impact T cells at one year post exposure. Additionally, pomalidomide is over a $2 billion drug and a critical backbone in second to fourth line with potential for increasing utilization accelerated by the need for T cell sparing therapies in the future. In summary, despite the headwinds in 2023, we continue to advance our mission for XPOVIO that every eligible patient with multiple myeloma should receive selinexor during their patient journey. Please advance now to Slide 10, and I'll turn the call over to Reshma to review our clinical pipeline progress.

泊馬度胺和 IMiD 對 T 細胞功能沒有潛在的負面影響，這與環磷酰胺等烷化劑不同，環磷酰胺等烷化劑在接觸一年後會影響 T 細胞。此外，泊馬度胺是一種價值超過 20 億美元的藥物，是第二至第四線的關鍵支柱，由於未來對 T 細胞保留療法的需求，其利用率有可能加速增加。總之，儘管 2023 年面臨困難，我們仍繼續推進 XPOVIO 的使命，即每位符合條件的多發性骨髓瘤患者都應在就診過程中接受 selinexor 治療。現在請前進到幻燈片 10，我會將電話轉給 Reshma，以審查我們的臨床管道進展情況。

Thank you, Sohanya. Starting off with an overview of our clinical pipeline on Slide 11. We are rapidly advancing our pipeline, which is evaluating 2 complementary novel sign compounds selinexor and eltanexor across multiple cancers of high unmet need, including myelofibrosis, myelodysplastic neoplasms, endometrial cancer and multiple myeloma. Turning now to Slide 12. We continue to optimize the dose of selinexor across our clinical programs. The lower doses of 40 or 60 milligrams weekly that are incorporated in all of our current selinexor clinical trials. A 1/4 to less than half of the original approved dose of 80 milligrams twice weekly. The substantially lower doses optimize the patient benefit by improving its tolerability ultimately enabling patients to stay on therapy longer and improving their overall benefit.

謝謝你，索哈尼婭。首先概述幻燈片 11 中我們的臨床產品線。我們正在快速推進我們的產品線，該產品線正在評估 2 種互補的新型標誌化合物 selinexor 和 eltanexor，用於治療多種需求未得到滿足的癌症，包括骨髓纖維化、骨髓增生異常腫瘤、子宮內膜癌和多發性骨髓瘤。現在轉向幻燈片 12。我們繼續在整個臨床項目中優化 selinexor 的劑量。我們目前所有的 selinexor 臨床試驗均採用每週 40 或 60 毫克的較低劑量。每週兩次，最初批准劑量 80 毫克的 1/4 至一半以下。顯著降低的劑量通過提高其耐受性來優化患者的利益，最終使患者能夠更長時間地接受治療並提高他們的整體利益。

I'm going to spend most of my time today talking about our recent data in myelofibrosis and myelodysplastic neoplasms. But first, on Slide 14, it is worth reviewing some of the evidence about the potential benefit of selinexor in T cell fitness. There are a number of published studies, which have shown that selinexor maintains a T cell function in mice and can help maintain the effectiveness of CAR-T therapies in mice pretreated with selinexor. To further expand on these data, we are collaborating with academic institutions on additional preclinical research studies to further explore the impact of signed mechanisms on T cell fitness.

我今天將花大部分時間討論我們最近在骨髓纖維化和骨髓增生異常腫瘤方面的數據。但首先，在幻燈片 14 上，值得回顧一下有關 selinexor 對 T 細胞健康的潛在益處的一些證據。有許多已發表的研究表明，selinexor 可以維持小鼠體內的 T 細胞功能，並且可以幫助維持 CAR-T 療法在經過 selinexor 預處理的小鼠中的有效性。為了進一步擴展這些數據，我們正在與學術機構合作開展更多臨床前研究，以進一步探討簽名機制對 T 細胞適應性的影響。

In addition, we are leveraging real-world evidence data to determine whether patients who were treated with selinexor prior to receiving CAR-Ttherapy benefit from improved outcomes with CAR-T. Lastly, we are evaluating multiple clinical studies that will evaluate the benefit of selinexor when used before or after BCMA or CAR-T therapy in patients with multiple myeloma.

此外，我們正在利用真實世界的證據數據來確定在接受 CAR-T 治療之前接受 selinexor 治療的患者是否受益於 CAR-T 治療結果的改善。最後，我們正在評估多項臨床研究，這些研究將評估在 BCMA 或 CAR-T 治療之前或之後對多發性骨髓瘤患者使用 selinexor 的益處。

This body of evidence will enhance our understanding of the role of XPO1 inhibition has in maintaining the T cell environment, which may potentially augment the benefit achieved with subsequent T cell therapies. Now let's discuss the data that we presented a few weeks ago at AACR on the efficacy and safety of selinexor plus ruxolitinib in first-line myelofibrosis patients. Since we already discussed these data at the event we hosted on April 18, I will cover these slides quickly.

這些證據將增強我們對 XPO1 抑制在維持 T 細胞環境中的作用的理解，這可能會增強後續 T 細胞療法所取得的益處。現在讓我們討論幾週前在 AACR 上提供的有關 selinexor 聯合魯索替尼在一線骨髓纖維化患者中的療效和安全性的數據。由於我們已經在 4 月 18 日舉辦的活動中討論了這些數據，因此我將快速介紹這些幻燈片。

For anyone looking for additional details, I would encourage you to listen to a replay of our webcast from April 18, which is available in the Events and Presentations section of our website. Turning to Slide 16. The only approved class of therapy in myelofibrosis is the JAK inhibitors.

對於任何想要了解更多詳細信息的人，我建議您收聽 4 月 18 日起的網絡廣播重播，您可以在我們網站的“活動和演示”部分找到該廣播。轉向幻燈片 16。唯一獲得批准的治療骨髓纖維化的療法是 JAK 抑製劑。

Less than 50% of patients achieved in SVR35 and TSS50, and there are notable subgroups, including men and those who start on low dose of ruxolitinib were fewer than 25% achieved in SVR35 at week 24. And First, let's turn to Slide 17, which shows the trial design for our Phase I 034 study from which the efficacy and safety data for the selinexor plus ruxolitinib combination have been observed.

在 SVR35 和 TSS50 中實現 SVR35 和 TSS50 的患者不到 50%，並且有一些值得注意的亞組，包括男性和開始使用低劑量魯索替尼的患者，在第 24 週時在 SVR35 中實現的患者不到 25%。 首先，讓我們轉向幻燈片 17，該圖顯示了我們 I 034 期研究的試驗設計，從中觀察到了 selinexor 與 ruxolitinib 組合的療效和安全性數據。

On Slide 18 are the SVR35 and TSS50 results broken down by dose. In the efficacy evaluable in ITT populations, the SVR35 rate at week 24 achieved in the 60 milligram dose cohort were 92% and 79%, respectively, which is almost double compared to the rates achieved at 40 milligrams. Furthermore, these reductions occurred rapidly with a 71% SVR35 rate observed at week 12 in the 60 milligram ITT patient population.

第 18 張幻燈片是按劑量細分的 SVR35 和 TSS50 結果。在 ITT 人群中可評估的療效中，60 毫克劑量組在第 24 週實現的 SVR35 率分別為 92% 和 79%，幾乎是 40 毫克劑量組實現的比率的兩倍。此外，這些減少發生得很快，在 60 毫克 ITT 患者群體中，第 12 週觀察到的 SVR35 率為 71%。

Consistent with the SVR35 data, treatment with the 60 milligram dose showed greater symptom improvement compared to patients treated with the 40-milligram dose. At week 24 for patients who received a 60 milligram dose of selinexor, TSS50 was observed in 78% of the efficacy evaluable population and 58% of the ITT population.

與 SVR35 數據一致，與 40 毫克劑量治療的患者相比，60 毫克劑量治療的患者症狀改善更大。在第 24 週，接受 60 毫克劑量的 selinexor 的患者中，78% 的療效可評估人群和 58% 的 ITT 人群中觀察到 TSS50。

Here as well, you see rapid improvement in symptoms with approximately 67% of the ITT population who received selinexor 60 milligrams achieved a TSS50 as early as week 12. The waterfall on Slide 19 shows the spleen volume response and the efficacy evaluable patients. As you can see, 100% of the evaluable patients treated with selinexor 60 milligrams achieved a spleen volume response of 35% or more at any time.

在這裡，您也可以看到症狀迅速改善，大約 67% 接受 selinexor 60 毫克的 ITT 人群早在第 12 週就達到了 TSS50。幻燈片 19 上的瀑布圖顯示了可評估患者的脾臟體積反應和療效。正如您所看到的，使用 selinexor 60 毫克治療的可評估患者中，100% 在任何時間都實現了 35% 或更高的脾臟體積反應。

Moving to Slide 20. We have the subgroup data in patients treated with selinexor 60 milligrams. In general, efficacy was similar across all of the subgroups that were evaluated. Highlighted in Orange are 2 important subgroups, specifically the response rates for men and women in the ITT population, which were similar at 78% and 80%, respectively. Similar efficacy was also observed by ruxolitinib starting dose with patients who were treated at starting doses of 15 or 20 milligrams of ruxolitinib achieving an SVR35 of 75% as compared to 83% amongst patients treated with 5 or 10 milligrams of ruxolitinib.

轉到幻燈片 20。我們有接受 selinexor 60 毫克治療的患者的亞組數據。一般來說，所有接受評估的亞組的療效相似。橙色突出顯示了 2 個重要的亞組，特別是 ITT 人群中男性和女性的反應率，分別為 78% 和 80%。魯索替尼起始劑量也觀察到了類似的療效，以 15 或 20 毫克魯索替尼起始劑量治療的患者的 SVR35 為 75%，而用 5 或 10 毫克魯索替尼治療的患者的 SVR35 為 83%。

On Slide 21, we show a unique subgroup analysis from patients that had their ruxolitinib dose reduced to 5 milligrams as early as cycle 2 and remain on that dose for the remaining duration of their therapy. Even with the subtherapeutic dose of ruxolitinib, all patients evaluable at week 24 achieved a spleen volume reduction of 35% or more. Similarly, symptom score improvement was observed in all patients with 5 out of 6 patients achieving a 50% or greater improvement in their total symptoms.

在幻燈片 21 中，我們展示了對患者進行的獨特亞組分析，這些患者早在第 2 個週期就將魯索替尼劑量減少至 5 毫克，並在剩餘的治療期間保持該劑量。即使使用亞治療劑量的魯索替尼，所有在第 24 周可評估的患者的脾臟體積也減少了 35% 或更多。同樣，所有患者的症狀評分均得到改善，其中 6 名患者中有 5 名的總症狀改善了 50% 或更高。

These data suggest that XPO1 is a fundamental mechanism in myelofibrosis. Slide 22 presents a breakdown of adverse events. The most common adverse events were nausea, anemia, fatigue and thrombocytopenia and the most common grade 3/4 AEs were anemia, thrombocytopenia and neutropenia. While 75% of patients experienced nausea, the vast majority of these events were Grade 1 and transient with the majority of these events resolving within 2 cycles. Amongst the patients who received one prophylactic antiemetic, nausea rates was decreased and occurred at only a Grade 1 severity.

這些數據表明 XPO1 是骨髓纖維化的基本機制。幻燈片 22 詳細介紹了不良事件。最常見的不良事件是噁心、貧血、疲勞和血小板減少，最常見的 3/4 級 AE 是貧血、血小板減少和中性粒細胞減少。雖然 75% 的患者經歷了噁心，但絕大多數這些事件都是 1 級且短暫的，其中大多數事件在 2 個週期內得到緩解。在接受一種預防性止吐藥的患者中，噁心發生率有所下降，且嚴重程度僅為 1 級。

We anticipate that these rates will further decrease in the Phase III study, which will incorporate mandatory dual antiemetics for the first 2 cycles. On Slide 23, even though some patients experienced nausea and vomiting, there was a median absolute weight gain of 2.5 kilograms observed at week 24 in patients treated with selinexor 60 milligrams.

我們預計這些比率將在第三階段研究中進一步下降，該研究將在前兩個週期中納入強制性雙重止吐藥。在幻燈片 23 中，儘管一些患者出現噁心和嘔吐，但在第 24 週觀察到接受 60 毫克 selinexor 治療的患者的中位絕對體重增加了 2.5 公斤。

As shown on Slide 24, we highlight the potential findings for disease modification given that the median hemoglobin levels return to baseline and there's a rapid normalization of platelet levels contrast this with findings from patients who have received ruxolitinib as a single agent where hemoglobin levels drop after treatment initiation and stay low.

如幻燈片 24 所示，我們強調了疾病修正的潛在發現，因為中位血紅蛋白水平恢復到基線，並且血小板水平迅速正常化，這與接受魯索替尼作為單藥治療的患者的發現形成對比，其中血紅蛋白水平在接受魯索替尼治療後下降。開始治療並保持低水平。

The increase in hemoglobin over time, coupled with the rapid normalization of platelet levels between cycles 2 to 3 may be evidence of disease modification. Critical finding for patients given that thrombocytopenia is the leading cause for ruxolitinib discontinuation. In summary, as we turn to Slide 25, we believe selinexor 60 milligrams in combination with ruxolitinib has the potential to transform frontline myelofibrosis treatment paradigms. The combination is generally well tolerated and manageable, allowing most patients to remain on therapy.

隨著時間的推移，血紅蛋白的增加，加上第 2 至 3 個週期之間血小板水平的快速正常化，可能是疾病緩解的證據。鑑於血小板減少症是魯索替尼停藥的主要原因，這對患者來說是一項重要發現。總之，當我們轉向幻燈片 25 時，我們相信 selinexor 60 毫克與魯索替尼聯合有潛力改變一線骨髓纖維化治療模式。該組合通常具有良好的耐受性和可控性，允許大多數患者繼續接受治療。

Rapid, deep and sustained spleen response and robust symptom improvement was found in patients treated with selinexor 60 milligrams in combination with ruxolitinib appearing to work together synergistically. As seen on Slide 26, the planned Phase III trial will enroll JAK inhibitor naive patients with intermediate and high-risk myelofibrosis, 306 patients will be randomized 2:1 to ruxolitinib plus selinexor or ruxolitinib plus placebo. We are eagerly looking forward to initiating the Phase III trial this quarter.

在使用 selinexor 60 毫克與魯索替尼聯合治療的患者中發現了快速、深入和持續的脾臟反應以及強勁的症狀改善，這似乎具有協同作用。如幻燈片 26 所示，計劃中的 III 期試驗將招募未接受過 JAK 抑製劑治療的中危和高危骨髓纖維化患者，306 名患者將按 2:1 隨機分配至魯索替尼加 selinexor 或魯索替尼加安慰劑。我們熱切期待本季度啟動第三階段試驗。

Now let's turn our attention to our research in patients with myelodysplastic neoplasms or MDS, starting on Slide 28. Between 12,000 to 20,000 people in the United States are expected to have been diagnosed with higher-risk MDS in 2022. Hypomethylating agents are the current standard of care for newly diagnosed higher-risk MDS patients. However, only approximately 50% of patients respond. Prognosis and higher-risk relapsed/refractory disease is poor with an expected overall survival of only 4 to 6 months, and there are currently no approved therapies for HMA refractory MDS.

現在讓我們將注意力轉向我們對骨髓增生異常腫瘤或 MDS 患者的研究，從幻燈片 28 開始。預計到 2022 年，美國將有 12,000 至 20,000 人被診斷出患有高風險 MDS。去甲基化藥物是當前的標準新診斷的高危 MDS 患者的護理。然而，只有大約 50% 的患者有反應。預後和高風險復發/難治性疾病很差，預計總生存期僅為 4 至 6 個月，而且目前尚無批准的 HMA 難治性 MDS 治療方法。

Given the importance of XPO1 inhibition in MDS, eltanexor has the potential to meaningfully improve survival and provide benefit to patients who are in need of effective therapies. Turning to Slide 29. You can see the design of our Phase II study of eltanexor in relapsed/refractory higher-risk MDS. The data that we will be discussing today is from the 30 patients enrolled as part of the Phase II interim analysis.

鑑於 XPO1 抑制在 MDS 中的重要性，eltanexor 有潛力顯著提高生存率，並為需要有效治療的患者帶來益處。轉向幻燈片 29。您可以看到我們 eltanexor 治療復發/難治性高風險 MDS 的 II 期研究的設計。我們今天討論的數據來自 II 期中期分析中納入的 30 名患者。

All patients were treated with the recommended Phase II dose of eltanexor identified in the Phase I, which was 10 milligrams daily for 5 days of each week. As shown on Slide 30, the objective response rate observed in the ITT population was 27%. All of the responses were marrow CRs with 2 of these patients also achieving hematologic improvement.

所有患者均接受 I 期試驗中推薦的 eltanexor II 期劑量治療，即每天 10 毫克，每週 5 天。如幻燈片 30 所示，ITT 人群中觀察到的客觀緩解率為 27%。所有緩解均為骨髓 CR，其中 2 名患者還實現了血液學改善。

Noteworthy was the transfusion independence rate observed in 29% of the patients who were transfusion dependent on red blood cells or platelets at baseline. The median overall survival was 8.7 months, which is encouraging given the median overall survival for patients with higher-risk relapsed or refractory MDS is typically only 4 to 6 months. Finally, on Slide 31, side effects were generally tolerable and manageable.

值得注意的是，在基線時依賴紅細胞或血小板輸血的患者中有 29% 觀察到輸血獨立率。中位總生存期為 8.7 個月，鑑於高風險復發或難治性 MDS 患者的中位總生存期通常僅為 4 至 6 個月，這一結果令人鼓舞。最後，在幻燈片 31 上，副作用通常是可以忍受和控制的。

The most common AEs were asthenia, diarrhea and nausea, the most common grade 3 plus AEs were neutropenia, thrombocytopenia and asthenia. There were no treatment-related adverse events leading to death, and 3 patients discontinued due to a treatment-related adverse event. Overall, the data from our interim analysis points to the potential importance of XPO1 inhibition in MDS. We plan to study these data further and determine the optimal development plan for eltanexor in MDS in the second half of this year. With that, please turn to Slide 32, and I will now hand it over to Mike.

最常見的 AE 是乏力、腹瀉和噁心，最常見的 3 級以上 AE 是中性粒細胞減少、血小板減少和乏力。沒有導致死亡的治療相關不良事件，3 名患者因治療相關不良事件而停藥。總體而言，我們的中期分析數據表明 XPO1 抑制在 MDS 中的潛在重要性。我們計劃在今年下半年進一步研究這些數據並確定 eltanexor 在 MDS 中的最佳開發計劃。現在請轉到幻燈片 32，我現在將其交給 Mike。

I hope everyone is having a great morning, and thank you, Reshma. Turning to our financials since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which begin on Slide 33. Total revenue for the first quarter of 2023 was $38.7 million compared to $47.7 million for the first quarter of 2022. Net product revenue from U.S. commercial sales of XPOVIO for the first quarter of 2023 was $28.3 million compared to $28.3 million for the first quarter of 2022. As Sohanya discussed, net product revenue was adversely affected by more patients using our patient assistance program as well as higher gross to net discounts, which were 24% for the quarter. We now expect our gross to net discounts will be near the higher end of our range of 20% to 25% this year.

我希望每個人都有一個美好的早晨，謝謝你，Reshma。談到我們的財務狀況，自從我們今天早些時候發布了包含完整財務業績的新聞稿以來，我將只關注從幻燈片 33 開始的要點。2023 年第一季度的總收入為 3870 萬美元，而第一季度的總收入為 4770 萬美元。 2022 年第一季度 XPOVIO 在美國商業銷售的淨產品收入為 2830 萬美元，而 2022 年第一季度為 2830 萬美元。正如 Sohanya 所討論的，更多患者使用我們的患者援助對產品淨收入產生了不利影響計劃以及更高的毛淨折扣（本季度為 24%）。我們現在預計今年的總折扣與淨折扣將接近 20% 至 25% 範圍的上限。

Turning to costs. With our continued disciplined execution, we are pleased to be delivering a combined 16% year-over-year reduction in our R&D and SG&A expenses this quarter. As we have discussed in the past, we have a focused pipeline and you are seeing this in our R&D spend. R&D expenses for the first quarter of 2023 were $32.3 million, down 23% compared to $42.1 million for the first quarter of 2022.

轉向成本。憑藉我們持續嚴格的執行力，我們很高興本季度的研發和銷售及管理費用同比減少了 16%。正如我們過去所討論的，我們有一個專注的管道，您可以在我們的研發支出中看到這一點。 2023 年第一季度的研發費用為 3230 萬美元，比 2022 年第一季度的 4210 萬美元下降 23%。

Likewise, SG&A expenses for the first quarter of 2023 were $35.9 million, down 7% compared to $38.8 million for the first quarter of 2022. We are achieving this through purposeful and comprehensive spend discipline, which includes the accelerated closure of our noncore programs while simultaneously rapidly advancing 3 pivotal Phase III programs. Cash, cash equivalents, restricted cash and investments as of March 31, 2023, totaled $261.9 million compared to $279.7 million as of December 31, 2022. As Sohanya outlined, we are lowering both our total revenue and XPOVIO net product revenue ranges by $15 million, primarily due to the higher-than-anticipated use of our patient assistant programs and associated free drug.

同樣，2023 年第一季度的銷售管理及行政費用為 3590 萬美元，比 2022 年第一季度的 3880 萬美元下降 7%。我們通過有目的和全面的支出紀律來實現這一目標，其中包括加速關閉我們的非核心項目，同時快速推進3個關鍵的三期項目。截至 2023 年 3 月 31 日，現金、現金等價物、限制性現金和投資總額為 2.619 億美元，而截至 2022 年 12 月 31 日為 2.797 億美元。正如 Sohanya 所說，我們將總收入和 XPOVIO 淨產品收入範圍降低了 1500 萬美元，主要是由於我們的患者助理計劃和相關免費藥物的使用量高於預期。

In 2024, we expect this to improve with fewer patients utilizing our path for co-pay assistance due to IRA-related redesign of Part D benefits. With these changes, we are now guiding to total revenue of $145 million to $160 million for 2023 and U.S. XPOVIO net product revenue of $110 million to $125 million. On the cost side, as we've accelerated our closure of nonpriority programs and disciplined expense management, we are also lowering our expense guidance by $15 million.

到 2024 年，由於 IRA 相關的 D 部分福利重新設計，我們預計這種情況會有所改善，利用我們的途徑獲得共同支付援助的患者將會減少。通過這些變化，我們目前的目標是 2023 年總收入為 1.45 億至 1.6 億美元，美國 XPOVIO 產品淨收入為 1.1 億至 1.25 億美元。在成本方面，隨著我們加快關閉非優先項目和嚴格的費用管理，我們還將費用指導降低了 1500 萬美元。

We now anticipate non-GAAP R&D and SG&A expenses which excludes stock-based compensation expense to be in the range of $245 million to $260 million for the full year of 2023. And finally, that our existing cash, cash equivalent investments as well as the revenue we expect to generate from XPOVIO product sales and other license revenues will be sufficient to fund our planned operations into late 2025. We I'll now flip to Slide 34 and turn the call over to Richard for some final thoughts. Richard?

我們現在預計 2023 年全年的非 GAAP 研發和 SG&A 費用（不包括基於股票的薪酬費用）將在 2.45 億美元至 2.6 億美元之間。最後，我們現有的現金、現金等價物投資以及我們預計從 XPOVIO 產品銷售和其他許可收入中獲得的收入將足以為我們到 2025 年底的計劃運營提供資金。我現在將翻到幻燈片 34，並將電話轉給 Richard，以徵求一些最終想法。理查德？

Thank you, Mike. Turning to Slide 35. As we have discussed today, we are rapidly advancing our pipeline with 3 Phase III programs to potentially expand our commercial indications as we demonstrate the benefit that XPO1 inhibition can deliver to patients in areas with high unmet need. We continue to expand on our foundation in multiple myeloma and believe that every eligible patient should receive selinexor during their patient journey. I would like to thank our teams that continue to execute in a disciplined manner and who strive each day for patients with high unmet needs as we work to generate value for patients and shareholders. Thank you again for joining us today. And I would now like to ask the operator to open the call up to the Q&A portion of today's call. Operator?

謝謝你，邁克。轉向幻燈片 35。正如我們今天所討論的，我們正在通過 3 個 III 期項目快速推進我們的管道，以潛在地擴大我們的商業適應症，因為我們證明了 XPO1 抑制可以為需求未得到滿足的地區的患者帶來好處。我們繼續擴大在多發性骨髓瘤領域的基礎，並相信每位符合條件的患者都應該在就診過程中接受 selinexor 治療。我要感謝我們的團隊，他們繼續以嚴格的方式執行工作，每天都在為患者和未滿足的高需求而努力，同時我們努力為患者和股東創造價值。再次感謝您今天加入我們。我現在想請接線員將電話打開到今天電話的問答部分。操作員？

(Operator Instructions) Our first question comes from Peter Lawson from Barclays.

（操作員說明）我們的第一個問題來自巴克萊銀行的 Peter Lawson。

I wonder if you could just add to it on free drug and pack program, is that still increasing? And where do you think that could be as you kind of exit 2Q? And then for Mike, what do you think the revenue impact in the quarter was from the PAP free drop program and gross to net?

我想知道您是否可以將其添加到免費藥品和包裝計劃中，這一數字還在增加嗎？當你退出第二季度時，你認為這可能會發生在哪裡？那麼對於 Mike，您認為 PAP 免費投放計劃對本季度收入的影響以及總收入對淨收入的影響如何？

Sure, Peter, thanks for the question. I mean, I think, broadly, as you heard from Sohanya, there was a real unprecedented increase in the use of the PAP programs during the period, and historically, it's been about 5% and now in April approached about 20%. So obviously, we've built that range into our guidance with our guidance coming at the higher end, if there's less patients having to access our patient assistance program versus more towards the mid- to lower end, if it continues at the same rates as it is. And then maybe I'll turn to Mike to talk about the impact with regards to gross to net.

當然，彼得，謝謝你的提問。我的意思是，我認為，總的來說，正如您從 Sohanya 那裡聽到的那樣，在此期間 PAP 計劃的使用確實出現了前所未有的增長，從歷史上看，這一數字約為 5%，現在 4 月份接近 20% 左右。顯然，我們已將這一範圍納入我們的指導中，如果必須使用我們的患者援助計劃的患者較少，我們的指導將處於高端，而如果其繼續以與這是。然後也許我會請邁克談談對毛淨值的影響。

I think, Peter, your question was on the impact on PAP for the quarter?

Peter，我想您的問題是對本季度 PAP 的影響？

Yes, and the gross to net. So if there's -- you can break out the revenue impact.

是的，還有毛淨額。因此，如果有的話，您可以列出收入影響。

Yes. So our gross to net for the quarter was about -- was 24%, which is about 5 points higher year-over-year. So we're guiding on the call today -- we're keeping our range of 20% to 25%, but we're guiding that it will be on the higher end of that range for the rest of the year. And as far as PAP direct impact on the quarter, it was a hair over $1 million or so in Q1. So the impact is more forward-looking as Sohanya mentioned in her script on where these foundations or when these foundations would open for the year. So it's not a massive impact on Q1, but it was more forward-looking.

是的。因此，我們本季度的毛淨比約為 24%，比去年同期高出約 5 個百分點。因此，我們今天的電話會議指導意見是——我們將保持 20% 至 25% 的範圍，但我們的指導意見是，今年剩餘時間裡，該範圍將處於該範圍的高端。就 PAP 對本季度的直接影響而言，第一季度的影響超過 100 萬美元左右。因此，正如 Sohanya 在她的劇本中提到的，這些基金會在哪里或這些基金會今年何時開放，其影響更具前瞻性。所以這對第一季度的影響並不大，但更具前瞻性。

And then just on the foundations, is there any change there going forward? I mean -- and is that -- is that spend being more focused around BCMA versus other therapies, do you think?

那麼在基礎上，未來會有什麼變化嗎？我的意思是——您認為，與其他療法相比，這些支出是否更集中在 BCMA 上？

Yes, Peter, we don't really obviously have insight into what kind of patients are accessing the foundation's programs. So I think as we touched on, obviously, the foundations play a really important role, supporting patients with financial assistance that you have access to that assistance and especially in the Medicare Part D, patients who need co-pay assistance, especially with regards to looking at what's happening to patients as they transition into a 5% extra cost moving forward.

是的，彼得，我們顯然並不了解什麼樣的患者正在訪問基金會的項目。因此，我認為正如我們所談到的，基金會顯然發揮著非常重要的作用，為您可以獲得經濟援助的患者提供支持，特別是在 Medicare D 部分中，為需要共同支付援助的患者提供支持，特別是在以下方面：看看患者在過渡到 5% 的額外費用後會發生什麼情況。

And so as we talked about, looking at 2024, moving forward, kind of this catastrophic coverage of the 5% co-pay was the change driven through the IRA changes that we expect will require less patients to access patient assistance programs.

因此，正如我們所討論的，展望 2024 年，展望未來，5% 共付額的災難性覆蓋是通過 IRA 變化推動的變化，我們預計將需要更少的患者獲得患者援助計劃。

Got it. Okay. And I guess just a final question just for, Mike, around cost savings, whether that impacts SG&A or R&D and kind of how that kind of filters through to programs in the second half?

知道了。好的。我想最後一個問題是邁克，關於成本節約，這是否會影響銷售、行政管理或研發，以及這種影響如何滲透到下半年的計劃中？

Yes. The big part of it is really acceleration of closing our nonprioritized program. So that's really the focus in order to bring down the R&D side of expense. And of course, we have our 2 ongoing Phase IIIs and one to start. So it's a mix across all 3 areas of R&D, commercial and SG&A, but it's a combination of cost discipline and acceleration of the closure of the nonpartisan program.

是的。其中最重要的部分實際上是加速關閉我們的非優先計劃。因此，這確實是降低研發費用的重點。當然，我們還有兩個正在進行的第三階段，還有一個即將啟動。因此，它是研發、商業和 SG&A 三個領域的混合體，但它是成本紀律和加速結束無黨派計劃的結合。

Our next question comes from the line of Maurice Raycroft from Jefferies.

我們的下一個問題來自傑富瑞 (Jefferies) 的莫里斯·雷克羅夫特 (Maurice Raycroft)。

This is Kevin on for Maurice. First question I had was on myeloma. You pointed out that almost 60% of the new patient share is from the earlier line setting versus, I believe, around 55% or close to that earlier this year. could you say what proportion of that is due to volume increase in the earlier line or whether that's primarily due to increased competition in the later line.

這是莫里斯的凱文。我的第一個問題是關於骨髓瘤。您指出，近 60% 的新患者份額來自早期的線路設置，而我相信，這一比例約為 55% 或接近今年早些時候的水平。您能否說一下，其中有多少比例是由於較早生產線的銷量增加，還是主要由於較晚生產線的競爭加劇所致。

I think, Kevin, maybe I'll turn to Sohanya to expand on that.

我想，凱文，也許我會請索哈尼亞來詳細闡述這一點。

So yes, so 60% -- we are approaching 60% of XPOVIO new patient starts moving into the earlier lines. and that means that -- the remainder of the patients are in the fourth line, fifth line plus. Now that is driven by primarily in the community where we are seeing an increased use of XPOVIO as well as use in the earlier lines.

所以是的，所以 60%——我們正在接近 60% 的 XPOVIO 新患者開始進入早期的生產線。這意味著——其餘的患者都在第四線、第五線以上。現在，這主要是由社區推動的，我們看到 XPOVIO 以及早期產品線的使用有所增加。

Okay. Great. And then just on the dose response relationship that you saw in turning to myelofibrosis in the Phase I and the 60 milligram versus the 40 milligram doses. What would you expect or what do you expect in the ongoing endometrial and myeloma Phase IIIs where you're running studies at lower doses than you previously looked at?

好的。偉大的。然後是劑量反應關係，您在 I 期中看到的骨髓纖維化以及 60 毫克與 40 毫克劑量之間的關係。您對正在進行的子宮內膜和骨髓瘤 III 期臨床試驗（您正在以比您之前觀察的劑量更低的劑量進行研究）有何期望？

Yes, Reshma, do you want to expand on that?

是的，Reshma，你想擴展一下嗎？

Yes. Great question, Kevin. So what you can see across all of our programs, myelofibrosis, endometrial in multiple myeloma. We've incorporated these lower doses of either 40 milligrams or 60 milligrams dose weekly. A lot of that really suggests that regardless of tumor type, you can drive efficacy again with these lower doses of selinexor. Now there are going to be differences, right? Given the underlying tumor type, whether it's a monotherapy or in combination, but what we are triangulating around is that these, again, lower doses, improve the tolerability, enable patients to stay on therapy and, of course, ultimately drive that efficacy.

是的。好問題，凱文。所以您可以在我們所有的項目中看到，骨髓纖維化、多發性骨髓瘤中的子宮內膜。我們每週服用 40 毫克或 60 毫克的較低劑量。其中很多確實表明，無論腫瘤類型如何，您都可以使用這些較低劑量的 selinexor 再次提高療效。現在會有差異，對嗎？考慮到潛在的腫瘤類型，無論是單一療法還是聯合療法，但我們正在三角測量的是，這些再次降低劑量，提高耐受性，使患者能夠繼續治療，當然，最終推動療效。

So it is nice to see that consistency again in that positive benefit risk around these lower doses of selinexor regardless of tumor types.

因此，很高興看到無論腫瘤類型如何，這些較低劑量的 selinexor 的積極獲益風險再次保持一致。

Great. Just a final quick follow-up for ASCO. You have a myelofibrosis post through there. Should we expect any new data in terms of maybe durability or dose intensity or anything like that?

偉大的。這只是 ASCO 的最後一次快速跟進。那裡有一個骨髓纖維化柱。我們是否應該期待任何關於耐久性或劑量強度或類似數據的新數據？

We haven't guided on the actual content of ASCO. Again, we did have a recent presentation, as you know, at SVR the February data cut. But with that said, we're always going to have opportunities to provide additional data, whether it's from an efficacy, safety or translational from this Phase I given that we follow patients long term and have collected multiple samples. So again, can't comment specifically at what's going to happen at ASCO, but there are going to be new data, and we hope to be able to present new data over the course of the next 6, 12, 18 months from the study.

我們還沒有對 ASCO 的實際內容進行指導。正如您所知，我們最近在 SVR 上確實做了一次關於 2 月份數據削減的演示。但話雖如此，鑑於我們長期跟踪患者並收集了多個樣本，我們總是有機會提供額外的數據，無論是療效、安全性還是第一階段的轉化數據。再說一遍，我無法具體評論 ASCO 將會發生什麼，但將會有新的數據，我們希望能夠在接下來的 6、12、18 個月的研究過程中提供新數據。

Our next question comes from the line of Mike Ulz from Morgan Stanley.

我們的下一個問題來自摩根士丹利的 Mike Ulz。

This is [Gunjan] online for Mike. I just have a question about this PAP program utilization. So where do you see the main driving factor of the increasing like from 5% to 20% within just 2 months? And although you said like in 2024, you are expecting like lowering utilization. What do you see the evolving in the next 3 quarters and maybe beyond 2024?

我是 Mike 的在線 [Gunjan]。我只是對這個 PAP 程序的使用有疑問。那麼，您認為在短短 2 個月內從 5% 增長到 20% 的主要驅動因素在哪裡？儘管您說的是 2024 年，但您預計利用率會降低。您認為未來 3 個季度甚至 2024 年之後會發生什麼變化？

Yes, Sohanya, do you want to touch on that?

是的，Sohanya，你想談談這個嗎？

Yes. So the main driver in terms of the significant increase in the utilization of PAP was driven by particularly the Medicare Part D patients. Now our PAP program provides free drug to qualified uninsured and uninsured patients broadly, but this includes Medicare Part D patients that need financial assistance with their 5% beneficiary coinsurance requirement above the catastrophic cover threshold. Now this segment of patients were a particular driver in terms of financial assistance that they needed and the impact that we saw as a result of the foundation closure.

是的。因此，PAP 使用率顯著增加的主要驅動因素尤其是醫療保險 D 部分患者。現在，我們的 PAP 計劃向符合資格的未投保和未投保患者廣泛提供免費藥物，但這包括需要經濟援助且其 5% 受益人共同保險要求高於災難性承保閾值的 Medicare D 部分患者。現在，就他們所需的經濟援助以及我們看到的基金會關閉所產生的影響而言，這部分患者是一個特殊的推動者。

Now looking into 2024, this is the piece that is eliminated in the redesign of the Part D benefits per the IRA. So the 5% beneficial coinsurance requirement above the catastrophic coverage threshold is eliminated. So that segment of patients will lead less financial assistance and less reliance on patient assistance programs in 2024. As for the remainder of this year, again, as Richard commented earlier, we've incorporated into the guidance range, this uncertainty factor on where the foundations can support new patients for the rest of the year as well as the guidance incorporates the year-to-date impact of path as well as subsequent refills.

現在展望 2024 年，這是根據 IRA 重新設計 D 部分福利時被取消的部分。因此，超過災難承保閾值 5% 的有益共同保險要求被取消。因此，到 2024 年，這部分患者將獲得更少的經濟援助，並減少對患者援助計劃的依賴。至於今年剩餘時間，正如理查德早些時候評論的那樣，我們已將這一不確定因素納入指導範圍。基金會可以在今年剩餘時間內為新患者提供支持，並且該指南納入了 Path 的年初至今的影響以及隨後的補充。

Our next question comes from the line of Colleen Kusy from Baird.

我們的下一個問題來自貝爾德 (Baird) 的科琳·庫西 (Colleen Kusy)。

On XPOVIO ex U.S., can you talk about some of the drivers there? And what gives you confidence in hitting the ex U.S. portion of your guidance regarding?

在 XPOVIO ex U.S. 上，您能談談那裡的一些驅動程序嗎？是什麼讓您有信心達到指導中的前美國部分？

Yes. Thanks, Colleen. When you look at what's happening ex U.S., as we've talked to maybe the commercial launches have taken place in Germany and Austria. Menarini is working through the pricing reimbursement process in the EU this year and over the next kind of 12 months. I think in those markets, obviously, they were able to launch in the second-line plus indication to start. So I think that enables them to move forward, I think, with the earnings we have here in the U.S. and a more rapid uptake.

是的。謝謝，科琳。當你看看美國以外發生的事情時，正如我們所說，商業發布可能已經在德國和奧地利進行。美納里尼 (Menarini) 正在研究今年和未來 12 個月在歐盟的定價報銷流程。我認為，顯然，在這些市場中，他們能夠在二線產品中推出加上適應症。因此，我認為這使他們能夠憑藉我們在美國的盈利和更快的吸收而向前發展。

And I think when we look at outside of the U.S., also we know in Asia Pac. XPOVIO is commercially available in Mainland China, Australia, South Korea, Singapore and Taiwan. The commercial launch in Mainland China took place in May of '22. And at the same time, they're working through the China NRDL strategy. It's under evaluation depending on label expansion and timing and further discussion with the China authority. So I think our partners across the globe, making really good progress with regards to moving forward from a commercial launch perspective.

我認為，當我們看看美國以外的地區時，我們也知道亞太地區的情況。 XPOVIO 已在中國大陸、澳大利亞、韓國、新加坡和台灣上市。 2022 年 5 月在中國大陸推出商用。與此同時，他們正在實施中國國家醫保目錄戰略。目前正在根據標籤擴展和時間安排以及與中國當局的進一步討論對其進行評估。因此，我認為我們在全球的合作夥伴在從商業發布的角度取得了非常好的進展。

Great. That's helpful. And then just based on the MDS data that you put out this week, what are the potential next steps for that program? And are any of those next steps currently included in your cash guidance?

偉大的。這很有幫助。然後，根據您本週發布的 MDS 數據，該計劃的後續潛在步驟是什麼？目前您的現金指導中是否包含這些後續步驟？

Colleen, I'll take that one. And thanks for the question. So yes, encouraged by the data that we reported from the interim analysis, just to provide background again and to highlight this is a very hard-to-treat patient population. We enrolled these higher-risk relapsed/refractory MDS patients. overall survival is very poor, unfortunately, at 4 to 6 months.

科琳，我要那個。謝謝你的提問。所以，是的，受到我們從中期分析中報告的數據的鼓舞，只是為了再次提供背景並強調這是一個非常難以治療的患者群體。我們招募了這些高風險的複發/難治性 MDS 患者。不幸的是，總生存期很差，只有 4 到 6 個月。

So again, encouraged by those 8, 8.7 median overall survival that we observed from the interim, also encouraged by the ORR. We're going to take a look at these data interrogate them further and define the next steps in the next half of the second year. I'll turn the financial question over to Mike.

再次，受到我們中期觀察到的 8、8.7 中位總生存期的鼓舞，也受到 ORR 的鼓舞。我們將進一步研究這些數據，並在第二年下半年確定下一步的步驟。我會將財務問題轉交給邁克。

Colleen, we do have some eltanexor costs in our cash guidance. Ultimately, depending what happens with the MDS program is where those costs will be. But for now, we have some probablized placeholders for sure.

科琳，我們的現金指導中確實有一些 eltanexor 成本。最終，這些成本將取決於 MDS 計劃的情況。但就目前而言，我們肯定有一些可能的佔位符。

Understood. And last question, just on myelofibrosis and the competitive landscape there. I know we're going to get some Phase III data by the end of this year from the MANIFEST-2 study. How do you expect that data would impact your development and regulatory plans in myelofibrosis?

明白了。最後一個問題是關於骨髓纖維化和那裡的競爭格局。我知道我們將於今年年底從 MANIFEST-2 研究中獲得一些 III 期數據。您預計這些數據將如何影響您在骨髓纖維化方面的開發和監管計劃？

Yes, great question. So at a high level, I don't think it really impacts what we do with our Phase III, again, very encouraged by the Phase I data. Right now, our entire focus is really initiating the Phase III, which we anticipate is going to start this quarter and being able to enroll the trial. With that said, I think looking at the data, I think, regardless of what the manifest data look like potential way to transform, we have an opportunity to be best-in-class and to really transform the first-line myelofibrosis space, not only based upon the numerical SVR and TSS50 data that we. Presented at week 24 but also the very important improvement in cytopenias given the underlying disease modification that our current data suggests.

是的，很好的問題。因此，從高水平來看，我認為這不會真正影響我們在第三階段所做的事情，同樣，第一階段的數據非常鼓舞人心。目前，我們的全部重點實際上是啟動第三階段，我們預計該階段將於本季度開始並能夠註冊試驗。話雖如此，我認為從數據來看，無論明顯的數據看起來是什麼樣的潛在轉型方式，我們都有機會成為一流的並真正改變一線骨髓纖維化領域，而不是僅基於我們的 SVR 和 TSS50 數值數據。在第 24 週出現，但考慮到我們當前數據表明的潛在疾病改變，血細胞減少症也得到了非常重要的改善。

But also importantly, the fact that we potentially may have monotherapy activity with selinexor. And those data are really based upon that suboptimal ruxolitinib data in which efficacy is preserved for both SVR and TSS50 even when the ruxolitinib doses are reduced all the way down to 5 milligrams.

但同樣重要的是，我們可能會使用 selinexor 進行單一療法。這些數據實際上是基於次優的魯索替尼數據，其中即使魯索替尼劑量一路減少至 5 毫克，SVR 和 TSS50 的功效仍得以保留。

That affords physicians a lot of flexibility to potentially discontinue ruxolitinib due to, let's say, toxicity and continue a patient on with selinexor. So again, I think there's a lot of differentiating factors with selinexor plus ruxolitinib that can potentially enable it to be a best-in-class really regardless of what happens with some of the other competitors.

這為醫生提供了很大的靈活性，可以因毒性等原因停止魯索替尼治療，並繼續對患者使用 selinexor。再說一遍，我認為 selinexor 加魯索替尼有很多差異化因素，無論其他一些競爭對手發生什麼情況，它都有可能成為同類最佳藥物。

Our next question comes from the line of Chris Raymond from Piper Sandler.

我們的下一個問題來自 Piper Sandler 的 Chris Raymond。

This is Nicole Gabreski on for Chris. Sorry if I missed this, but just as we think about the rest of the year in terms of guidance, I guess, is there any certain quarter where most of the impact of these headwinds stuck might be recognized? Or I guess, how should we be thinking about that?

我是克里斯的妮可·加布雷斯基。抱歉，如果我錯過了這一點，但正如我們在指導方面思考今年剩餘時間一樣，我想是否有某個特定季度可以認識到這些逆風的大部分影響？或者我想，我們應該如何思考這個問題？

And then just quickly for myelofibrosis. Just as we look at other myelofibrosis programs and development, those tend to have a single primary endpoint of SVR35. Can you just maybe talk about the rationale or drivers behind having co-primary endpoints for your Phase III study?

然後很快就可以治療骨髓纖維化。正如我們觀察其他骨髓纖維化項目和開發一樣，這些項目往往只有一個主要終點：SVR35。您能否談談 III 期研究共同主要終點背後的基本原理或驅動因素？

Thanks, Nicole. I'll comment on the first and then turn it over to Reshma. But when you look at the evolution over quarters, I think you can expect your kind of consistent differences that you see quarter-over-quarter in line with our historical patterns. And then as we talk to looking at the impact of patient assistance programs, we just need to see how that evolves during the year, and that's obviously something which we have to see what comes in, in terms of patients requiring resistance through our programs.

謝謝，妮可。我將對第一個進行評論，然後將其交給 Reshma。但當你觀察幾個季度的演變時，我認為你可以預期你所看到的季度與季度之間的一致差異，與我們的歷史模式一致。然後，當我們談論患者援助計劃的影響時，我們只需要看看這一年的發展情況，這顯然是我們必須看到的，就患者需要通過我們的計劃進行抵抗而言。

And as we've said in our guidance range, with less patients having to access our patient assistance program that will move us towards the higher end. And if we continue to see high rates of patients accessing our patient assistance program that moves us towards the middle to lower end. And Reshma, do you want to expand on the second part of the question?

正如我們在指導範圍中所說，越來越少的患者需要使用我們的患者援助計劃，這將使我們邁向高端。如果我們繼續看到高比例的患者接受我們的患者援助計劃，那麼我們就會走向中低端。 Reshma，您想詳細闡述問題的第二部分嗎？

Yes, absolutely. And thank you for the question, Nicole. So we're really focused on 2 main endpoints, the SVR35 and TSS50 ultimately for the patients, it's really critical that we show significant improvement in both of those endpoints. Of course, the SVR is a potential surrogate for overall survival. That reduction is key and showing a significant improvement, potentially overall long-term improvement for the patient.

是的，一點沒錯。謝謝你的提問，妮可。因此，我們真正關注的是 2 個主要終點，即最終為患者提供的 SVR35 和 TSS50，我們在這兩個終點上顯示出顯著的改善非常重要。當然，SVR 是總體生存率的潛在替代指標。這種減少是關鍵，並且顯示出顯著的改善，對患者來說可能是整體長期改善。

Of course, that symptoms, it affects directly how they feel. So again, we're focused on both of those endpoints, the data to date and the Phase I really suggests that we can maximize benefit for both of these endpoints compared to ruxolitinib and it's going to be our focus in our Phase III trial as well.

當然，這些症狀會直接影響他們的感受。因此，我們再次關注這兩個終點，迄今為止的數據和第一階段確實表明，與魯索替尼相比，我們可以最大限度地提高這兩個終點的效益，這也將成為我們第三階段試驗的重點。

Our next question comes from the line of Eric Joseph from JPMorgan.

我們的下一個問題來自摩根大通的埃里克·約瑟夫（Eric Joseph）。

Just following up on the commercial outlook with XPOVIO in 2024. I guess that you anticipate less PAP utilization. But outside of that, can you just comment on expectations on net pricing. We typically have seen some price hike, can you just kind of comment on whether those would actually flow through ultimately on the net price?

只是跟進 2024 年 XPOVIO 的商業前景。我猜您預計 PAP 利用率會降低。但除此之外，您能否評論一下對淨定價的預期。我們通常會看到一些價格上漲，您能否評論一下這些價格最終是否會真正反映在淨價上？

And then for eltanexor, I know that you're -- it sounds like you're just -- you're currently evaluating sort of the development path forward there. Is combination therapy part of the consideration there? Can you just talk about the potential combination path with eltanexor.

對於 eltanexor，我知道你——聽起來你只是——你目前正在評估那裡的發展道路。聯合治療是考慮的一部分嗎？您能談談與 eltanexor 的潛在組合路徑嗎？

Yes, maybe I'll turn it to Sohanya for the first part of that and then Reshma on the second part.

是的，也許我會把第一部分交給 Sohanya，然後將第二部分交給 Reshma。

Yes. Thanks, Eric, for the question. Again, in terms of 2024, we're not providing guidance for 2024 revenues. To your point, in 2024, because of that IR-related change, we do expect to see significantly fewer patients utilizing carryforward co-pay assistance in that segment that we discussed earlier. Again, we don't comment on future pricing strategy for 2024. But as far as growth in 2024, again, growth potential for mid to long term, I remain confident in our growth potential.

是的。謝謝埃里克提出的問題。同樣，就 2024 年而言，我們不會提供 2024 年收入指引。就您的觀點而言，由於 IR 相關的變化，我們預計到 2024 年，在我們之前討論的該細分市場中使用結轉共付援助的患者將顯著減少。同樣，我們不對 2024 年的未來定價策略發表評論。但就 2024 年的增長而言，中長期的增長潛力，我對我們的增長潛力仍然充滿信心。

And I can take the next one, Eric. Thank you for the question. Great question. Yes, as you noted, like we're not talking about the next steps in the development at this time. With that said, the fact that eltanexor showing monotherapy activity in this hard-to-treat patient population, just gives us a lot of flexibility in terms of next steps in our development, whether it's continuing to evaluate monatherapy, looking at different patient populations or to your point, potentially even looking at combinations. So again, lots of opportunities.

我可以接受下一個，埃里克。感謝你的提問。很好的問題。是的，正如您所指出的，就像我們現在不談論開發的後續步驟一樣。話雖如此，事實上 eltanexor 在這一難以治療的患者群體中顯示出單一療法活性，這一事實為我們的後續開發步驟提供了很大的靈活性，無論是繼續評估單一療法、研究不同的患者群體還是根據你的觀點，甚至可能會考慮組合。話又說回來，機會很多。

But again, it's built upon the foundation that eltanexor does have monotherapy activity. And in addition, the myelofibrosis is now showing in this different tumor type that XPO1 is a fundamental mechanism in this hard-to-treat cancer.

但同樣，它是建立在 eltanexor 確實具有單一療法活性的基礎上的。此外，在這種不同的腫瘤類型中，骨髓纖維化現在表明 XPO1 是這種難以治療的癌症的基本機制。

Our next question comes from the line of Jonathan Chang from SVB Leerink.

我們的下一個問題來自 SVB Leerink 的 Jonathan Chang。

This is Matt Kaufer on for Jonathan. Just first one, any updates on the regulatory interactions for the myelofibrosis Phase III? And are you able to discuss any of the statistical assumptions behind the study? And then I have a follow-up.

我是馬特·考弗 (Matt Kaufer) 替喬納森 (Jonathan) 發言。只是第一個，關於骨髓纖維化 III 期監管相互作用的任何更新嗎？您能討論一下這項研究背後的統計假設嗎？然後我有一個後續行動。

Sure, Matt, I'll turn to Reshma for that.

當然，馬特，我會向瑞什瑪求助。

Yes. Thanks, Matt, for the question. So we've had productive discussions with the FDA and have incorporated their feedback into our design. We don't talk about any specifics of those FDA interactions. And as I mentioned earlier on the call, really our focus at this point is initiating this trial likely this quarter.

是的。謝謝馬特提出的問題。因此，我們與 FDA 進行了富有成效的討論，並將他們的反饋納入我們的設計中。我們不會談論 FDA 相互作用的任何細節。正如我之前在電話會議中提到的，我們目前的重點實際上是可能在本季度啟動這項試驗。

In terms of the statistical assumptions, so there too, we haven't disclosed any of the details. With that said, we're looking very closely not only at the data that we've absorbed as part of our Phase I for both SVR and TSS50, but also looking at the historical data that we know that ruxolitinib has provided, again, for both of those endpoints. So really have utilized those data to ultimately design the most efficient trial that can enable this treatment to patients who have myelofibrosis.

就統計假設而言，我們也沒有透露任何細節。話雖如此，我們不僅非常仔細地研究我們在 SVR 和 TSS50 的第一階段中吸收的數據，而且還研究我們知道 ruxolitinib 再次提供的歷史數據。這兩個端點。因此，我們確實利用這些數據最終設計出最有效的試驗，使骨髓纖維化患者能夠接受這種治療。

Great. That's very helpful. And then just following up on the eltanexor data that you just released. I noticed there was a high degree of sensoring in some of the survival data. I was wondering if you could provide any color on those patients and what happened with them? And then also if you're able to provide any detail on the patient experience, for patients that were post both venetoclax and azacitidine.

偉大的。這非常有幫助。然後跟進您剛剛發布的 eltanexor 數據。我注意到一些生存數據中有高度的傳感。我想知道你能否提供這些患者的顏色以及他們發生了什麼？另外，如果您能夠提供有關接受維奈托克和阿扎胞苷治療後的患者體驗的任何詳細信息。

Yes. Great question. So we still have quite a few patients who are still in survival follow-up, Hence, one of the reasons that they are censored. This trial is ongoing. We continue to follow those patients for survival. And hopefully, we'll have an opportunity to present updated survival over the course of the next few months.

是的。很好的問題。所以我們還有相當多的患者仍在進行生存隨訪，這也是他們受到審查的原因之一。該審判正在進行中。我們將繼續追踪這些患者的生存情況。希望我們有機會在接下來的幾個月內展示最新的生存情況。

In terms of the post venetoclax, azacitidine. So great point. And this is a key differentiation from our Phase I study and that we had a subgroup of patients who did receive prior venetoclax, which is a BCL2, a smaller subgroup of patients who received the combination of venetoclax plus HMA inhibitors. Why is this such a important point? Largely because there are some preliminary data coming out of MD Anderson that suggests that patients who have received prior BCL2 may have poor prognosis compared to the already very poor prognosis in relapsed/refractory MDS.

就後維奈托克而言，阿扎胞苷。非常重要的一點。這是與我們的 I 期研究的一個關鍵區別，我們有一個先前接受過 Venetoclax（BCL2）治療的患者亞組，這是一個接受 Venetoclax 加 HMA 抑製劑聯合治療的較小患者亞組。為什麼這是如此重要的一點？很大程度上是因為 MD 安德森的一些初步數據表明，與復發/難治性 MDS 的預後已經非常差的患者相比，先前接受過 BCL2 治療的患者的預後可能較差。

So this is something that we're looking at more closely but again, gives us opportunity to further develop eltanexor, especially as venetoclax and azacitidine is expected to move as a new potential first-line therapy, leaving a gap, right, to further develop new therapies in this relapsed refractory space.

因此，這是我們正在更密切關注的事情，但同樣，這給了我們進一步開發 eltanexor 的機會，特別是因為 Venetoclax 和阿扎胞苷預計將成為一種新的潛在一線療法，從而為進一步開髮留下了空白。針對這個複發難治性空間的新療法。

Thank you. Ladies and gentlemen, this concludes our question and answer session. I would like to turn the conference back to Mr. Richard Paulson for any closing remarks.

謝謝。女士們先生們，我們的問答環節到此結束。我想請理查德·保爾森先生在會議上發表閉幕詞。

Thank you, operator, and thank you again to everyone for joining today's call. And we're wishing everyone a great day.

謝謝接線員，並再次感謝大家參加今天的電話會議。我們祝愿大家度過愉快的一天。

Thank you. The conference of Karyopharm has now concluded. Thank you for attending today's presentation. You may now disconnect your lines.

謝謝。 Karyopharm 會議現已結束。感謝您參加今天的演講。您現在可以斷開線路。