キャリオファーム（KPTI）2026年第2四半期決算説明会：セリネキサーのsNDAと流動性に焦点

主要なポイント

• 2026年第2四半期の売上高は3,340万ドルとなり、前年同期の3,790万ドルから減少しました。米国の「エクスポビオ（XPOVIO）」純製品売上高は前年同期の2,970万ドルから3,080万ドルに増加しました。
• カリオファーム（Karyopharm）は、FDAの迅速承認枠組みに基づき、骨髄繊維症に対するセリネキソルとルキソリチニブの併用療法に関する適応追加申請（sNDA）を2026年8月に提出する予定通りに進めています。
• SENTRYの申請は主に24週時点のSVR35結果に基づきます。トップライン解析における全生存期間のハザード比は0.43であり、成熟しつつあるSENTRYの生存データが確認的証拠として機能すると期待されています。
• 子宮体がんを対象とした第III相XPORT-EC-042試験は、mITT集団における主要評価項目で統計的有意性を達成できませんでした。カリオファームは同プログラムへの投資を削減し、骨髄繊維症と多発性骨髄腫の優先順位を上げています。
• 四半期末時点の流動性は総額6,540万ドルで、現在の事業計画では2026年9月までの資金を賄える見込みです。9月10日に1,580万ドルのタームローン元本返済期日が控えており、足元での資金調達リスクおよび財務制限条項（コベナント）リスクが生じています。
• 経営陣は、米国のエクスポビオ純製品売上高1億1,500万ドル〜1億3,000万ドルを含む、2026年通期の総売上高見通し（1億3,000万ドル〜1億5,000万ドル）を再確認しました。

主要財務データ

事業および業績の動向

骨髄繊維症に関する規制当局申請プログラム

カリオファームによると、セリネキソルのsNDA申請文書の大部分は完成しています。残された作業は、確認データ計画および統計解析に関してFDAと最終調整を行うことが中心となっています。

申請はSENTRY試験における24週時点のSVR35データに焦点を当てます。経営陣によると、併用療法は24週時点でルキソリチニブ単独療法と比較して約2倍の脾臓奏効率を示し、奏効は12週目までに現れ、36週目まで維持されました。

ルキソリチニブの1日平均投与量が15mg未満の患者において、SVR35率はルキソリチニブ単独での0%に対し、併用療法では50%に達しました。また、同社はトップライン解析における全生存期間のハザード比0.43や、併用療法による高い変異アレル頻度の減少率も強調しました。

カリオファームは、迅速承認が得られた場合、その後の臨床的有用性を確認するためにSENTRY試験の成熟しつつある全生存期間データが利用されると考えています。フォローアップが継続される中、患者、治験実施者、および同社の関係者は引き続き二重盲検状態を維持しています。

経営陣は、今後のマイルストーンとして、医学書（コンペンディア）や治療ガイドラインへの掲載、FDAによる申請受理、優先審査の可能性、早ければ2027年第1四半期にも予想される承認および発売を挙げています。ただし、これらはすべて外部審査や規制当局の判断に委ねられています。

商業的機会とXPOVIO

経営陣の試算によると、承認された場合、セリネキソルとルキソリチニブの併用療法は米国で年間最大約10億ドルのピーク時売上高を創出する可能性があります。同社は米国で約20,000人の骨髄繊維症患者が存在し、毎年約4,000人が新たに一次治療を開始していると言及しました。

カリオファームは、地域医療機関や学術医療機関への展開、マーケットアクセス能力、患者支援プラットフォーム「KaryForward」など、既存のエクスポビオ血液がん領域インフラを活用する計画です。経営陣によると、骨髄繊維症患者の約70%が地域医療の現場で治療を受けています。

エクスポビオの米国における純製品売上高は3,080万ドルに達しました。同製品の米国ビジネスの約60%を地域医療が占めており、治療における競合が激化する中でも基調的な需要は安定していると経営陣は述べています。

子宮体がんプログラム

XPORT-EC-042試験では、セリネキソル群で無悪化生存期間の中央値に数値的な改善が見られたものの、mITT集団における主要評価項目で統計的有意性に達しませんでした。カリオファームは、短期的患者フォローアップと残りの治験活動の完了を継続しつつ、予定していた投資を大幅に縮小しています。

同社は、この決定によるより大きなコスト削減効果が2027年に現れると見込んでいます。

経営陣による業績見通し（ガイダンス）

今後2四半期のライセンスおよびその他の収益は、全額ロイヤルティで構成される見込みです。費用見通しには、子宮体がんプログラムや資金調達・戦略的取引の検討に伴い発生する可能性のある一部の一時的費用は含まれていません。

経営陣は、骨髄繊維症プログラム、EC-042試験の結果に伴う組織変更、および潜在的な資金調達や戦略的見直しに係るコストの影響で、第3四半期の費用が第2四半期よりもやや増加する可能性があると警告しました。

リスクと注視事項

• 現在の計画において、既存の流動性資金による事業継続は2026年9月までとなる見込みです。
• 2026年9月10日にシニア担保付タームローンに基づく1,580万ドルの元本返済が期日を迎えます。新たな資金調達や貸し手からの適用免除（ウェイバー）が得られない場合、流動性が最低コベナント要件である1,000万ドルを下回り、期限の利益喪失（デフォルト事由）を引き起こす可能性があります。
• カリオファームは資金調達の機会や戦略的代替案を検討していますが、経営陣は具体的な条件を開示しておらず、合意が締結されるかどうかについても確定していません。
• 迅速承認はFDAによるsNDAの審査に依存します。優先審査は申請時に要請する必要があり、FDAがその要請を評価するのに通常約60日かかります。
• 承認の継続には、SENTRY試験の長期的な全生存期間データを通じた臨床的有用性の確認が必要となりますが、データが成熟するまでに数年かかる可能性があると経営陣は指摘しています。
• ガイドラインやコンペンディアへの潜在的な掲載は独立した機関によって決定されるため、保証されているわけではありません。

アナリスト質疑応答のハイライト

• sNDA申請の準備状況：経営陣によると、申請文書の大部分は完成しています。最終作業は、確認的な全生存期間解析および統計計画についてFDAと調整を行うことです。
• 確認的証拠：現在進行中の二重盲検SENTRY試験により、迅速承認下で臨床的有用性を確認するために必要な成熟した全生存期間データが提供されると期待されています。
• 申請パッケージ：24週時点のSVR35が申請の主な根拠となり、奏効の持続性、全生存期間の知見、SVR35と生存期間の関係、病勢修飾データ、および安全性によって裏付けられます。48週時点の一部のデータが含まれる可能性はありますが、主な焦点ではありません。
• 優先審査：カリオファームは申請提出時に優先審査を要請する計画です。経営陣は、その要請の結果についてFDAから具体的な示唆は受けていないと述べています。
• 流動性に関する話し合い：経営陣は貸し手と直接対話を行っており、資金調達および戦略的代替案を検討していると述べましたが、交渉の詳細や改定される可能性のある義務については開示を控えました。
• ガイドラインへの掲載：カリオファームは、NCCNが独立した機関であることを認めつつも、2026年後半に決定が下される可能性を見込んでいます。

決算説明会（トランスクリプト）全文

決算説明会の完全なトランスクリプト

経営陣による説明

Operator

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 Therapeutics Second Quarter 2026 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 conference over to Brendan Strong, Senior Vice President, Investor Relations.

Brendan 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. 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.

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

While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any later date. I'll now turn the call over to Richard. Please turn to slide 5.

Richard Paulson

Thank you, Brendan, 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 III data set toward our planned supplemental new drug application under the FDA's Accelerated Approval Pathway for patients with myelofibrosis. Over the past several months, we've remained focused, moved with urgency, and executed against an ambitious plan from generating and presenting the SENTRY data to publishing the results in the Journal of Clinical Oncology to working collaboratively with the FDA to establish a regulatory pathway as we prepare our planned submission.

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. 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.

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.

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.

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 III XPORT-EC-042 study and the actions we've taken following those results. 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.

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. 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 support a rapid and efficient launch in myelofibrosis if approved.

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. 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 1 of the most important periods in its history. Turning to slide 8, over the coming quarters we expect several important milestones, beginning with the potential inclusion in the treatment guidelines and 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.

Additionally, we remain on track to report top-line data from the 60-milligram cohort of the Phase II 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. 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 novel therapeutic mechanism that has the potential to fundamentally change the treatment of patients with myelofibrosis. Reshma?

Reshma Rangwala

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. Turning to slide 10, the biological rationale for combining XPO1 and JAK inhibition is compelling. JAK-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.

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 1 third of patients. Overall survival improvements are limited, and meaningful modifications of the underlying disease is not observed. 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.

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.

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 0 observed with ruxolitinib alone, indicating that with the combination, SVR35 is driven by selinexor and supported by modest doses of ruxolitinib. 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. 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 I 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. Over the past several years, a substantial body of retrospective evidence from Phase III JAK inhibitor trials has demonstrated that greater SVR35 rate differences observed across the 2 arms correlate with improved overall survival. SENTRY now provides an important opportunity to build on that body of evidence as the first Phase III 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.

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. 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. 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. 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.

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. 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. As Richard noted, we expect top-line data from the 60-milligram cohort of SENTRY-2 during the second half of this year. Taken together, 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. With that, I'll turn the call over to Sohanya.

Sohanya Cheng

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. On the commercial side, we have established coverage in both community and academic hematology, key account capabilities, and market access expertise. And through KaryForward, 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.

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.

Importantly, while commercial promotion begins only following regulatory approval, scientific engagement is already well underway. Our 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.

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. 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.

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. 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.

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 U.S. alone.

Approximately 20,000 patients are currently living with myelofibrosis in the U.S. with roughly 4,000 newly treated frontline patients each year with no approved combination therapy in frontline myelofibrosis. 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. 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. 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 U.S. business, where physicians continue to value XPOVIO as a differentiated and convenient oral therapy. 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.

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.

Lori Macomber

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. The decrease reflects the conclusion of Menarini's reimbursement of development-related expenses at the end of 2025, which reduced revenue by approximately $6.5 million compared with the prior year quarter. U.S. 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.

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 III trials having completed enrollment. 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. 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.

As Richard discussed, we are actively evaluating a range of financing opportunities and strategic alternatives with the objective of extending our cash runway, preserving strategic flexibility and maximizing long-term shareholder value as we advance our myelofibrosis program.

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.

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, with 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.

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 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 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.

Richard Paulson

Thank you. 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. 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.

Operator

[Operator Instructions]

Your first question comes from Edward Tenthoff with Piper Sandler. Please go ahead.

質疑応答

Edward Tenthoff

I just had some questions with respect to what still had to be done for the 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 else 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?

Richard Paulson

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

Reshma Rangwala

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. One 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.

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.

Edward Tenthoff

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?

Reshma Rangwala

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

Edward Tenthoff

That's really helpful. Well, good luck.

Reshma Rangwala

Thank you.

Operator

Your next question comes from Ioannis Souroutzidis with Cantor.

Ioannis Souroutzidis

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 compendia could provide sufficient revenues to address the debt and operating needs? And I have a quick follow-up.

Richard Paulson

Yes, thanks, Yanni. I think as we've talked to, there's really, 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. 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.

Ioannis Souroutzidis

Yes, appreciate it. And then just, I guess, relatedly, too, 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.

Richard Paulson

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. 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, we'll be able to continue to execute on that and find the right balance as we move forward.

Ioannis Souroutzidis

Understood.

Richard Paulson

Thanks, Yanni.

Operator

Thank you. Your next question comes from Brian Abrahams with RBC Capital Markets.

Brian Abrahams

Congrats on the continued progress. 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.

Richard Paulson

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. 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. And for the second part, I'll turn to Reshma to talk to the FDA.

Reshma Rangwala

Yes, thanks, Brian. You know, so as I mentioned, really great productive conversations with the FDA. In terms of priority review, not necessarily. So this is, 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. 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.

Brian Abrahams

Super helpful.

Richard Paulson

Thanks, Brian.

Operator

Your next question comes from Maury Raycroft with Jefferies. Please go ahead.

Maurice Raycroft

Maybe I'll just ask 1 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.

Richard Paulson

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. 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.

Maurice Raycroft

Understood. That's helpful. And then for NCCN compendia 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 Compendia listing?

Richard Paulson

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. 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 III program.

Maurice Raycroft

Understood.

Richard Paulson

Thanks, Maury.

Operator

Your next question comes from Michael King with Rodman & Renshaw.

Michael King

Just a little further granularity on the filing and the interaction with the FDA. I'm just wondering, given the recent interaction with the B and C [ Type B and Type 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.

Richard Paulson

Yes, let me turn to Reshma for that part.

Reshma Rangwala

Yes, thanks, Michael. Great question. So the sNDA, 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. 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 SVR and 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.

Michael King

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

Reshma Rangwala

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.

Michael King

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

Reshma Rangwala

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 SVR and 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.

Michael King

Great.

Richard Paulson

Thanks, Michael.

Operator

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

Richard Paulson

Thank you, Operator, and thank you everyone for joining us today and your continued interest in Karyopharm. I guess we've highlighted, 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.

Operator

Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines. Have a great day.