Earnings Call Transcript - KPTI Q1 2026

Operator, Operator

Good morning, everybody. My name is Kelsy, and I will be your conference operator for today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics First Quarter 2026 Financial Results Conference Call. There will be a question-and-answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Mr. Brendan Strong, Senior Vice President, Investor Relations. Please go ahead.

Brendan Strong, Senior Vice President, Investor Relations

Good morning, and thank you all for joining us on today's conference call to discuss Karyopharm's first quarter 2026 financial results and recent company progress. We issued a press release this morning detailing our financial results for the first 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 seen on Slide 2, I'm joined by Richard, Reshma, Sohanya and Lori, who will provide an update on the results for the first quarter, highlight the importance of the results from our Phase III SENTRY trial in myelofibrosis and provide an update on our EC042 endometrial cancer program and related commercial opportunity. 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 in the future with the SEC. 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, President and Chief Executive Officer

Good morning, and thank you for joining us today. Karyopharm continues to execute through an important period for the company with the recent and upcoming milestones that we believe can unlock meaningful growth opportunities and shape our next phase. Over the past several quarters, we have focused our organization around three priorities: advancing our staged clinical programs, maintaining our commercial foundation in multiple myeloma and managing the business with discipline as we approach significant value-creating milestones. Since our fourth quarter call, we have made meaningful progress across our key 2026 priorities, including reporting top line results from our Phase III SENTRY trial in myelofibrosis, concluding enrollment in EC042 in endometrial cancer and strengthening our balance sheet through the financing completed in Q1. With these milestones and data in hand, we are now focused on the next phase of execution, advancing our regulatory and scientific engagement for SENTRY, preparing for the EC042 top line data readout and continuing to manage the business with financial discipline. SENTRY showed a compelling and differentiated profile for selinexor in combination with ruxolitinib, including rapid, deep and sustained spleen volume responses accompanied by a promising overall survival signal and evidence of potential disease modification, including greater reductions in variant allele frequency as early as week 24. These findings reinforce the potential of selinexor plus ruxolitinib to address an important gap in frontline myelofibrosis treatment, where treatment options remain limited, and the need for therapies that improve long-term outcomes remains high. We are very encouraged by the level of interest and enthusiasm we are hearing from the myelofibrosis key opinion leader and patient group communities following the SENTRY readout. Our next major catalyst is EC042 in endometrial cancer, where enrollment is now complete and we continue to expect top line data in mid-2026. This is a biomarker-driven program focused on patients with TP53 wild-type endometrial cancer, particularly those with MMR-proficient tumors where there remains a significant unmet need and no approved personalized biomarker-driven maintenance therapy. Commercially, we believe we have a strong foundation to build from. Our deep relationships across community and academic accounts and capabilities in sales, marketing, market access, patient support and medical affairs can be leveraged across future potential launches. In both endometrial cancer and myelofibrosis, we see concentrated treatment landscapes and clear unmet need. Financially, we remain disciplined. We ended the quarter with increased liquidity following our financing in March, and we continue to manage spending with a clear focus on the clinical and regulatory milestones that matter most. Our current operating plan provides us with sufficient flexibility through our major near-term clinical and regulatory catalysts, including SENTRY next steps and the EC042 top line readout, funding us into late Q3 2026. With that context, today's call will first cover the SENTRY highlights and next steps, followed by a deeper discussion of the upcoming EC042 readout, our commercial readiness and our financial performance with guidance. I'll now turn the call over to Reshma.

Reshma Rangwala, Chief Medical Officer

Thank you, Richard. Before we dive into myelofibrosis and endometrial cancer, I want to take a step back and ground everyone in the biology of XPO1 inhibition and why we believe this novel mechanism has the potential to meaningfully improve outcomes for patients across both diseases as outlined on Slide 7. What's particularly compelling about XPO1 inhibition is that it allows the drug to simultaneously impact multiple highly relevant oncogenic pathways. Selinexor selectively binds to XPO1, a key nuclear export protein, and blocks the transport of critical regulatory proteins out of the nucleus. By doing so, selinexor drives the retention and activation of tumor suppressor proteins such as p53, FoxO, T21 and IKBα within the nucleus where they can exert their anticancer effects. This effect is particularly notable for myelofibrosis and endometrial cancer, given that greater than 95% and 50% of these tumors, respectively, are p53 wild-type. At the same time, it reduces the activity of oncogenic signaling pathways, including NF-κB and β-catenin, which is of relevance to myelofibrosis. Induction of cell cycle arrest independent of the p53 pathway is also a critical pathway important to both endometrial cancer and myelofibrosis. The net effect is a coordinated biological response, including decreased tumor cell proliferation, increased apoptosis and ultimately, the potential for durable disease control. We believe this multi-pathway mechanism is a key differentiator for selinexor and underpins the breadth of activity we've observed across multiple cancers, including both MF and EC. With that backdrop, let's turn to myelofibrosis and why we believe the SENTRY data are so compelling as outlined on Slide 9. There remains a clear opportunity to improve upon the current standard of care. While JAK inhibitors have been an important advancement and remain the only approved class, we continue to see relatively low rates of spleen volume reduction, limited impact on long-term survival and minimal evidence of true disease modification. As such, there is an unmet medical need for therapies that go beyond symptom control and deliver deeper, more durable benefit, and improve long-term outcomes like overall survival. Moving to Slide 10. As I presented a few weeks ago, we're very encouraged by the top line results from our Phase III SENTRY trial. The combination of selinexor plus ruxolitinib delivered rapid and clinically meaningful spleen volume reduction as early as week 12. Importantly, that benefit was sustained through week 36. The co-primary endpoint of SVR35 at week 24 was 50% for the combination compared to 28% for ruxolitinib alone, corresponding to a statistically significant p-value of less than 0.0001. Our second co-primary endpoint was symptom improvement at week 24. While the difference in absolute Total Symptom Score was not statistically significant, patients in both arms experienced important and similar improvement from baseline. What we find particularly exciting is the intriguing signal of overall survival, arguably the most important outcome for patients with myelofibrosis. The combination of selinexor and ruxolitinib is the first potential treatment in myelofibrosis to suggest an overall survival improvement relative to standard of care. At the time of the top line data, the overall survival hazard ratio was 0.43 with a nominal p-value of 0.0222. In addition, post hoc analyses demonstrate that SVR35 predicts overall survival, consistent with published analyses in other myelofibrosis trials that have also shown the same. These findings underscore the importance of achieving rapid, deep and sustained SVR35. The greater proportion of patients on the combination arm, 32%, who experienced a variant allele frequency reduction of at least 20% may be indicative of an underlying effect on the disease biology, raising the potential for true disease modification. The rapidity at which we see these VAF reductions reflects the anticlonal attributes of selinexor and mirrors both the substantial improvement in SVR35 as early as week 12 and the early improvements in overall survival. Lastly, the combination demonstrated a generally manageable tolerability profile that was consistent with what we understand about each agent individually. We did not observe any new safety signals. Importantly, with the use of the lower dose of selinexor and prophylactic dual antiemetics, we've seen an improved tolerability compared to the Phase I study. We believe the combination of the XPO1 inhibitor selinexor and ruxolitinib delivers a very compelling and differentiated product profile with the potential to improve outcomes for patients with myelofibrosis. Turning to Slide 11. We're excited that these data have been selected for a late-breaking oral presentation at ASCO, and we expect to have a manuscript published in a peer-reviewed journal in the middle of 2026. Overall, we remain very encouraged by the SENTRY results and look forward to productive discussions with the FDA. Let's now turn to endometrial cancer and why we're so excited about selinexor's potential to address a clear and meaningful treatment gap, particularly for patients with p53 wild-type, MMR-proficient tumors. As highlighted on Slide 13, this is a large and well-defined patient population. Approximately half of the patients are p53 wild-type and about 80% have MMR-proficient tumors. Importantly, this is not a niche segment. It represents a substantial proportion of the overall endometrial cancer patients whose unmet need remains high. Equally important, molecular classification is already embedded in the standard of care today. That means clinicians are routinely identifying these patients in practice, which we believe positions selinexor very well for real-world adoption if our Phase III data are positive and pending regulatory approval. On Slide 14, we believe we have an opportunity to define a personalized biomarker-driven maintenance treatment option for patients with p53 wild-type endometrial cancer. Today, patients with advanced or recurrent EC have no personalized biomarker-driven maintenance-only therapy. And although checkpoint inhibitors are approved in combination with chemotherapy followed by checkpoint inhibitor alone, patients whose tumors are both p53 wild-type and MMR-proficient gained the least benefit. The RUBY trial, which evaluated dostarlimab in combination with chemotherapy in advanced or recurrent EC patients showed a marginal PFS improvement in patients whose tumors were NSMP or p53 wild-type MMR-proficient. This highlights the profound unmet need for the subgroup that comprises approximately 50% of all endometrial cancer patients and underscores the urgency to identify p53 wild-type–directed therapies. It also highlights the substantial benefit that potentially could be observed with selinexor in patients with p53 wild-type tumors and especially those whose tumors are both p53 wild-type and MMR-proficient. As seen on Slide 15, the top line data in the p53 wild-type subgroup of the SIENDO study showed a very strong PFS signal with the median PFS in the selinexor arm of 13.7 months versus 3.7 months for placebo, translating to a hazard ratio of 0.41. As you can see on Slide 16, with long-term follow-up, the median PFS benefit for the selinexor arm extends to 28.4 months corresponding to a hazard ratio of 0.44. And when we focus on the patients whose tumors are p53 wild-type and MMR-proficient, the data become even more compelling. As shown on Slide 17, the median PFS approaches 40 months at long-term follow-up with a PFS hazard ratio of 0.36. These results compare very favorably to the RUBY data in which the MMR-proficient p53 wild-type subgroup showed a PFS hazard ratio of 0.77. Taken together, what we see is not only a strong initial signal but a benefit that deepens and becomes more meaningful over time. That's the dynamic we're aiming to replicate in EC042. To demonstrate a clear PFS advantage at top line, we also anticipate that the PFS benefit may continue to strengthen as the data mature. The safety profile on Slide 18 is from the long-term follow-up from SIENDO. Given that the dose of selinexor was 80 milligrams in the SIENDO trial and prophylactic dual antiemetics for the first two cycles were not mandated, we have an opportunity to observe a better safety and tolerability profile in the ongoing EC042 trial. Similar to the SENTRY trial, we've been very deliberate in optimizing both the dose and supportive care. In the EC042 trial, selinexor is dosed at 60 milligrams once weekly, and we've mandated dual antiemetics during the first two cycles, which is when patients are most likely to experience nausea and vomiting. There is the potential that with an improved safety profile, patients stay on treatment longer translating to improved efficacy. Overall, we feel very good about how the program has evolved in delivering a more optimized and patient-friendly treatment approach. Finally, turning to Slide 19. As Richard mentioned, I'm very pleased that we have successfully completed enrollment in our Phase III EC042 trial. We enrolled 257 patients in the intent-to-treat population, with approximately 220 patients in the modified intent-to-treat population, which is the primary analysis population for the study. As a reminder, our statistical plan is designed to be both rigorous and efficient. We will first assess progression-free survival in the mITT population—if that analysis is statistically significant, the alpha will then pass down sequentially to the full ITT population. As we approach the prespecified number of PFS events that will trigger the primary analysis, we remain on track to report top line results in the near term. Stepping back, I'm incredibly excited about the opportunity in front of us, not only in endometrial cancer, but also in myelofibrosis. In both areas, we have the potential to establish new standards of care and deliver meaningful benefits for patients where significant unmet need remains.

Sohanya Cheng, Chief Commercial Officer

Thank you, Reshma. As shown on Slide 21, we delivered strong net product revenue growth this quarter, driven primarily by favorable gross-to-net dynamics, which Lori will cover in more detail. Underlying demand for XPOVIO was lower compared to the first quarter of 2025, reflecting the impact of new competitive entrants. This is not new territory for us. We've successfully navigated competitive dynamics and returned to drive demand growth. Turning to Slide 22. There are two ways that XPOVIO is positioned that we believe sets us up for future growth amidst an evolving and competitive landscape. First, our focus remains on the community setting, which represents approximately 60% of total U.S. sales where many community-based physicians and patients value XPOVIO as a flexible and convenient oral option in the second to fourth line. Second, our distinct positioning for XPOVIO as a differentiated mechanism of action in the peri–T-cell engaging therapy setting allows selinexor to be used in patients prior to a CAR T, which is an important position given anticipated future expansion of CAR Ts and also in patients progressing on a T-cell engaging therapy. Therefore, despite an evolving competitive landscape, we remain confident in our ability to drive growth in XPOVIO net product revenue. Now as we turn to Slide 23, if we look at our future potential launches in myelofibrosis and endometrial cancer, these are areas where there is strong overlap with community-based accounts with fewer treatment alternatives and higher unmet need than the multiple myeloma market. As we prepare for these potential launches, I would like to underscore the strength and value of our highly experienced teams. We have established capabilities across sales, marketing, market access and medical affairs, all of which can be utilized to educate on the relevant disease states. This allows us to prepare for launch with minimal incremental investment pre-approval and only modest additional spend post-launch. Let's now discuss the potential commercial opportunity in both myelofibrosis and endometrial cancer, starting with myelofibrosis on Slide 25. In myelofibrosis, the only treatment options that patients currently have are JAK inhibitors with ruxolitinib monotherapy being the standard of care for the past 15 years and only about one-third of patients that receive ruxolitinib achieve a spleen volume reduction of 35% or more with two-thirds of patients not adequately responding. Slide 26 provides an outline of the potential market opportunity. Selinexor plus ruxolitinib targets a sizable U.S. myelofibrosis market with roughly 20,000 patients living with the disease and limited approved options beyond JAK inhibitors. With around 7,000 newly diagnosed first-line patients annually, about 4,000 of whom are addressable, we see a clear path to meaningful adoption. We believe the combination of selinexor and ruxolitinib has the potential to deliver up to approximately $1 billion in U.S. peak annual revenue. Our sales organization is well positioned for a potential launch in myelofibrosis. We have deep relationships with the key accounts where the majority of patients are treated. As outlined on Slide 27, 70% of myelofibrosis patients are treated in the community setting and 30% are treated in academic centers. Across both settings the majority of patients are treated in a concentrated group of accounts, which enables us to move quickly and execute a focused, high-impact launch, if approved. Turning now to Slide 28. We're energized by the opportunity to reshape frontline myelofibrosis treatment by pairing selinexor with the current standard of care and, pending approval, to drive rapid uptake and potentially transform patient outcomes. Turning to Slide 30. I'd like to share how we are thinking about the commercial opportunity in endometrial cancer—which is the most common gynecologic malignancy in the United States with 17,000 newly diagnosed advanced or recurrent patients each year and incidence and mortality rates on the rise. As Reshma mentioned, we believe we have a clear opportunity to establish selinexor as the standard of care in patients whose tumors are p53 wild-type and MMR-proficient. These patients comprise approximately 50% of all endometrial cancer patients. As we look at other therapies that have driven meaningful benefit in the treatment landscape, for example, the uptake of checkpoint inhibitors in dMMR endometrial cancer and PARP inhibitors in the maintenance setting in ovarian cancer, they achieved peak share within 18 to 24 months of launch. Similarly, given the high unmet need for a maintenance therapy in p53 wild-type patients as well as our established commercial capabilities, we would expect adoption to be rapid. On duration, our assumptions are influenced by the fact that this would be a maintenance option. While we don't equate PFS directly with duration, the strength of our PFS data from SIENDO gives us confidence that patients can remain on therapy for an extended period. Putting this together, this represents a significant opportunity within a multibillion-dollar marketplace. Turning to Slide 31. In summary, from a commercial perspective, if approved, selinexor is positioned to rapidly transform treatment in p53 wild-type endometrial cancer. We're very encouraged by the opportunity ahead and confident in our commercial readiness to support successful launches. With that, I'll turn the call over to Lori starting on Slide 33.

Lori Macomber, Chief Financial Officer

Thank you, Sohanya, and good morning, everyone. I will focus on the key highlights from our first quarter financial performance and how those results position us relative to our full year expectations. Starting with revenue. Total revenue for the first quarter was $35.1 million compared to $30.0 million in the prior year period. U.S. XPOVIO net product revenue was $29.2 million compared to $21.1 million last year. This increase was driven by a decrease in gross-to-net, which was 21.8% this quarter versus 45% in the first quarter of 2025 and that was impacted by an atypical product return adjustment. Our gross-to-net reflected lower realized discounts and returns this quarter. Excluding these adjustments, our underlying gross-to-net was approximately 26% this quarter. Turning to expenses. We remain focused on disciplined execution. R&D expenses were $33.8 million, and SG&A expenses were $26.7 million, both relatively consistent year-over-year. This reflects our continued focus on prioritizing investment in our highest-value clinical programs while maintaining overall cost controls. Net loss was $22.4 million for the quarter compared to $23.5 million in the prior year. As a reminder, net loss includes noncash mark-to-market adjustments related to our financing structure. From an underlying operating perspective, performance improved meaningfully with a 20% reduction in loss from operations, driven by the increase in total revenue and continued expense discipline. Turning to the balance sheet. We are managing the business with a clear focus on our clinical catalysts and ended the quarter with $91.2 million in cash, cash equivalents and restricted cash which includes the approximately $50 million raised this quarter. Based on our current operating plan, we expect our existing liquidity to fund operations into late in the third quarter of 2026. We remain focused on prudent capital management, as we advance our pipeline and prepare for our upcoming Phase III readout in endometrial cancer. 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 three quarters and U.S. XPOVIO net product revenue of $115 million to $130 million. Finally, we also continue to expect combined R&D and SG&A expenses in the range of $230 million to $245 million in 2026. Overall, we believe our first quarter performance and operating discipline position us well to deliver against our full year expectations in 2026.

Richard Paulson, President and Chief Executive Officer

Thank you, Reshma, Sohanya and Lori. As we have discussed today, Karyopharm has made meaningful progress against the priorities we laid out entering 2026. Across both myelofibrosis and endometrial cancer, we believe the story is consistent. Selinexor has a differentiated mechanism of action, the clinical programs have been refined based on experience, and the commercial opportunities are meaningful. We have also worked hard to optimize how selinexor is used, including dose selection and proactive supportive care with the goal of delivering the right balance of efficacy, tolerability and real-world usability. Looking ahead, our focus is clear. We are advancing the next steps for SENTRY, including FDA engagement, presentation of the data at ASCO, publication planning and potential compendia inclusion. In endometrial cancer, we are preparing for the EC042 top line readout in mid-2026, which we believe represents a major potential value-creating catalyst for Karyopharm. Across the business, we will maintain operational and financial discipline as we execute while continuing to evaluate opportunities to strengthen our financial position and extend our runway. We have an important few months ahead and we are focused on executing with urgency, discipline and a clear commitment to bring meaningful new treatment options to patients in two areas of high unmet need. We'll now open the call for questions.

Operator, Operator

Your first question comes from Brian Abrahams from RBC Capital Markets.

Brian Abrahams, Analyst, RBC Capital Markets

Congrats on all the progress. So maybe just on the MF study. I guess, I'm wondering—have you done any additional work since the top line presentation to look into some of the deaths that occurred for patients on the placebo plus ruxolitinib arm relative to the selinexor plus ruxolitinib arm, anything standing out that wasn't apparent initially? And then anything—like, I guess, what should we be expecting beyond these initial top line data you reported at ASCO?

Richard Paulson, President and Chief Executive Officer

Yes. Thanks, Brian. I think overall, again, we'll have a totality of our results, as we shared at ASCO, but I'll turn to Reshma to expand on that.

Reshma Rangwala, Chief Medical Officer

Yes. Thanks, Brian, for the question. So absolutely, we're looking at the deaths that occurred—specifically the 23 deaths that were reported at the time of the top line. We haven't provided greater granularity in terms of the types of deaths or the distribution of deaths across the two arms. With that said, when I look at them, they're very consistent with what you would expect, not only in myelofibrosis, but in other oncology trials as well. So we're seeing deaths due to progression of disease, adverse events, etc. So nothing inconsistent with what you would expect, and more to come as we continue to evaluate these data. We'll certainly look at opportunities in which we can present it at upcoming medical congresses.

Operator, Operator

And your next question comes from Ted Tenthoff from Piper Sandler.

Edward (Ted) Tenthoff, Analyst, Piper Sandler

Great. Thank you very much, and thanks for all the updates—really an exciting time for Karyopharm and you guys just keep on fighting. So I appreciate that. I'm looking forward to the endometrial cancer data coming up. My question is on myelofibrosis and looking forward to the presentation at ASCO, can you give us a little bit more information about the potential timing or sort of preparation that you're doing for the meeting with the FDA, and when could we find out sort of where their head is on a potential sNDA, I think?

Richard Paulson, President and Chief Executive Officer

Yes. Again, I think overall, Ted, as we've shared, we're very pleased with the results and feel the SENTRY data is very compelling and meaningful for MF patients. I'll turn to Reshma again to expand on our planned engagement with the agency.

Reshma Rangwala, Chief Medical Officer

Yes, absolutely. And thank you, Ted, for the question. I just want to reiterate what Richard said. I think we're very compelled by the profile that we saw at the time of the top line results. It's not just about the spleen. We know that other Phase III trials have shown these spleen reductions. I think what is so compelling is that it's occurring in conjunction with this very promising overall survival signal, again as early as the data cutoff, and then it's reflected by this rapid VAF reduction, which again is a potential signal of disease modification. We believe this is happening because of the unique aspects of XPO1 inhibition that are specifically targeting the clone causing this anticlonal activity and again, reflected in the clinical endpoints of SVR, OS and this potential disease modification as well. We look forward to engaging with the FDA. They've been strong partners with us from the very beginning of the SENTRY trial. We hope to elaborate on our next steps over the course of the next couple of quarters.

Operator, Operator

And your next question comes from Colleen Kazi from Baird.

Nick, Analyst, Baird

Congrats on the progress. Just for myelofibrosis, could you discuss the gating factors for potential compendia inclusion for selinexor? And if selinexor is included in guidelines in the future, could you discuss how you view this opportunity versus an approval? And I just had a quick follow-up after that as well.

Reshma Rangwala, Chief Medical Officer

Sure. I'll take the first part of the question, and thank you, Nick, for this important question around compendia. We know that NCCN and other compendia are independent bodies. With that said, from our understanding, they're constantly looking at the literature—whether it's published literature, presented data—whether new treatments should be incorporated as part of their guidelines. We do expect that they will be well aware of the data that we present at ASCO in the next couple of weeks, and then any publication that we do anticipate should be published in the middle of the year. So we anticipate because of the importance of these data that they will be convening either ad hoc or at one of their scheduled meetings, and then hopefully, fingers crossed, they agree the data are compelling and will be incorporated into the guidelines. I'll let Richard take the second part of your question.

Richard Paulson, President and Chief Executive Officer

Yes, Nick, and on the second part, I think as you know, in myelofibrosis there is only one class of therapies historically, with ruxolitinib being approved over 15 years ago and a high unmet need for these patients. As Reshma has touched on, it's very typical in these areas with new data to work to get that guideline listing fairly rapidly. If you look at analogs over the years, drugs that received compendia listing have generated meaningful revenue based on physicians deciding to prescribe based on NCCN guidelines. So given the strong unmet need, I think you typically see if you only achieve NCCN listing without a label, products can achieve approximately about 50% of what peak may be if they had a label. This isn't an area that we would actively promote beyond what regulations allow, but it's an area where physicians can choose to use a medicine to make sure they're fulfilling the best interest of the patients. Great. And then just on the follow-up for the endometrial trial—with 257 patients enrolled in the ITT, that was just a bit under the 276 number originally, does that still provide sufficient powering to assess the broader ITT population?

Reshma Rangwala, Chief Medical Officer

Yes, I really appreciate the question, Nick. When we originally incorporated this new mITT population, that mITT population, by and large, consists of these patients who are going to be p53 wild-type and MMR-proficient. Yes, you can anticipate a small subgroup of patients whose tumors are MMR-deficient and are also medically eligible to receive a checkpoint inhibitor. But by and large, just assume this is going to be your p53 wild-type, MMR-proficient subgroup. When we originally incorporated that mITT, we assumed based upon our proportion that the 220 that we were targeting for that mITT would likely equate to approximately 276 patients in that ITT. What we found though is that the proportion was a little bit different. We are still very much targeting the 220 for the mITT, that's the key population for the FDA. And based upon the distribution, we ended up with 257 patients for the ITT. Because the benefit of selinexor is driven by the p53 status and not the MMR status, yes, we are very well powered to show meaningful benefit in both the mITT as well as the ITT populations.

Operator, Operator

Our next question comes from 'Jani.'

Jani, Analyst

A couple operational questions. Now that enrollment has completed here for the trial, looking back at the SIENDO results for endometrial cancer, outcomes really improved with additional follow-up. Can you at least directionally guide us in terms of thoughts on where median follow-up would fall here for this trial? Is it going to be closer to what we saw for SIENDO top line or maybe closer to the 30-plus month follow-up for the longer-term data cut? And a quick follow-up on myelofibrosis: with SENTRY2 slated to also put out data later this year, how does that integrate with the effort here to get a publication out and potentially be included in compendia listing?

Reshma Rangwala, Chief Medical Officer

I appreciate the question, Jani. We anticipate that EC042 is probably going to land between the two SIENDO cuts. We had top line results which showed a median PFS in that p53 wild-type subgroup of about 13.7 months, the subsequent cut demonstrated median PFS increased to approximately 22 months, and then the most recent long-term follow-up increased again to a median PFS of about 28 months. So over those cuts, we anticipate EC042 to likely land between the top line and the second cut. Ultimately, when we cut the data, it's going to be driven by when the events occur. Regarding SENTRY2, it's a very exciting trial because it demonstrates monotherapy activity of selinexor in a frontline population. I do want to reiterate it's not exactly the same population as SENTRY2 allows some patients with platelet counts as low as 50,000 to be enrolled, so slightly different. But it allows us to better understand monotherapy activity because investigators have the opportunity to add a JAK inhibitor as early as week 12, and we also get some important combination data. My hope is that these data collectively could significantly change the landscape in MF and potentially shift the paradigm to XPO1 inhibitors as a backbone. We look forward to presenting the SENTRY2 data in the second half of 2026, and pending the data, it could be meaningful for guideline consideration.

Richard Paulson, President and Chief Executive Officer

Thanks, Jani.

Operator, Operator

And your next question comes from Maurice Raycroft from Jefferies.

Maurice Raycroft, Analyst, Jefferies

Congrats on progress. When you meet with FDA on SENTRY, do you plan to share a more mature overall survival cut or other specific analyses, and who are you going to bring with you to the meeting? Also, is there more of an ex-U.S. interaction strategy you can share? Do you plan to meet with FDA first? Or do you want to align interactions with FDA and EMA?

Reshma Rangwala, Chief Medical Officer

Thanks, Maurice, for the question. Give me a chance to present the data at ASCO first. I don't want to get ahead of ourselves. There will be a lot of important data that Dr. Mascarenhas will present on behalf of all the investigators of SENTRY. As we reported a few weeks ago, the SVR data includes not only the week 24 data but also initial glimpses at week 36; we do have a bit longer follow-up for those endpoints. We haven't commented on any future data cuts yet, but the study was designed to follow for long-term outcomes, especially overall survival. Patients and physicians remain blinded to the arm to which they were randomized and will continue to follow for overall survival. We haven't guided on when subsequent steps or presentations will occur, but that is an opportunity based on the trial design. In terms of regulatory engagement, we look forward to providing updates over the course of the next quarters. At this point, we're not providing granular details around our conversations with the FDA or other global regulatory agencies.

Richard Paulson, President and Chief Executive Officer

Overall, our team is working with our partners globally, and we are preparing for an sNDA and working with regulatory agencies around the world to advance this rapidly given the high unmet need for these patients.

Maurice Raycroft, Analyst, Jefferies

Got it. That's helpful. And then maybe a quick follow-up—there's a SENTRY2 placeholder abstract at EHA and guidance for data in the second half—will the SENTRY2 data be at EHA or can you clarify?

Reshma Rangwala, Chief Medical Officer

Yes. That is a trial-in-progress abstract at EHA. We anticipate data from that trial in the second half of this year.

Operator, Operator

And your next question comes from Jonathan Chang from Leerink Partners.

Jonathan Chang, Analyst, Leerink Partners

First, can you remind me what dose is used in the EC042 study and how that compares to the SIENDO study, and what gives you confidence in the EC042 study dose? And as a follow-up to that, can you remind me what the safety profile in SIENDO looked like and what gives you confidence that patients can stay on selinexor in the maintenance setting for an extended period of time?

Reshma Rangwala, Chief Medical Officer

I appreciate the question, Jonathan. In SIENDO, the dose was 80 milligrams of selinexor once weekly and prophylactic dual antiemetic use was not consistently required in that protocol. In EC042, we optimized the regimen: the dose is 60 milligrams of selinexor once weekly and we require dual antiemetics during the first two cycles. We did this because nausea and vomiting are known side effects of selinexor, and those toxicities typically occur in the first two cycles. We mandated dual antiemetics for the first eight weeks and it is optional thereafter. How did we pick the dose? We looked at a comprehensive data set. In SIENDO, the median dose actually ended up being 60 milligrams for many patients because dose reductions occurred early largely due to GI and hematologic toxicity. We also reviewed clinical pharmacology data showing that the exposure at 60 milligrams overlaps substantially with 80 milligrams for the relevant pharmacodynamic effects. So we have a lot of confidence that 60 milligrams should improve the safety profile and enable patients to stay on treatment longer, which could translate to improved efficacy relative to what was observed in SIENDO. One other datapoint is SENTRY: that trial also incorporated 60 milligrams in combination with ruxolitinib and showed reductions in rates and grades of GI toxicities, especially nausea and vomiting, which supports the 60-milligram dose selection.

Operator, Operator

And your next question comes from Ted Tenthoff.

Edward (Ted) Tenthoff, Analyst, Piper Sandler

I didn't realize that there were openings at Karyopharm to submit my resume as well—especially in the commercial group, since that's going to be expanding. That was kind of my follow-up question—what additional prep are you guys doing both from a drug supply side as well as what kind of additions need to be made to the commercial organization if EC042 hits? And if you get on compendia or ultimately get approval in myelofibrosis, how does that change the organization?

Richard Paulson, President and Chief Executive Officer

Yes, I'll start, Ted. Great question, and I would love to talk further if you're interested. Overall, the organization is really well established. We've been working over the last couple of years to make sure we leverage the strong capabilities we've built from a supply perspective, with a solid supply chain and manufacturing readiness in the U.S. to support uptake for endometrial cancer and myelofibrosis as we work toward labels and commercialization in both areas. I'll turn to Sohanya to expand on the commercial preparations.

Sohanya Cheng, Chief Commercial Officer

Thanks, Richard. I'm very proud of the established team that we've set up, and there is a significant amount of prelaunch activity underway right now. I break it down into two components: global medical and scientific affairs has been engaging strongly with KOLs and has a strong presence at congresses to understand the treatment landscape and gather insights. From a commercial perspective, we've been developing messaging—both promotional and payer messaging—key account mapping, segmentation and so on. Lots of work is ongoing. As Rich mentioned, we have strong capabilities and customer-facing coverage at key accounts. Myelofibrosis is a very concentrated group of accounts, so we should be able to hit the ground running. For endometrial cancer and sales force coverage, we also have strong coverage at key academic and community medical oncology settings. For specialty gynecologic oncologists, there will be an incremental increase in sales coverage—this is a concentrated group of treating physicians. We're very excited coming from a position of strength and ready to expand the team as needed.

Operator, Operator

And your last question comes from Michael King from Rodman & Renshaw.

Michael King, Analyst, Rodman & Renshaw

A couple of quick ones, if I may. Just wondering, are the data that we'll see at ASCO going to closely map to what the FDA will see—meaning the FDA typically gets more data than what is public. In terms of data analysis and timing, will you take another product data cut before you present to the FDA after investors and your peers see it at ASCO?

Reshma Rangwala, Chief Medical Officer

Thanks for the question. We're not commenting on the specific data we will present to the FDA. In general, we'll provide greater clarity on our regulatory interactions and next steps over the coming quarters. We're excited about ASCO—the data will be presented publicly for the first time by Dr. Mascarenhas on behalf of the SENTRY investigators. It's a great opportunity for people to appreciate the benefit that selinexor in combination with ruxolitinib can provide and the key differentiating aspects of this combination relative to other treatments in myelofibrosis. I hope you can be there live.

Michael King, Analyst, Rodman & Renshaw

I wouldn't miss it for all the money. But to pick up on your comment about precedent, the FDA is precedent-driven. All the approved MF drugs have had some kind of a glitch in their data set. You guys didn't hit TSS maybe? But you did hit VAF and survival. Can you help put this in context relative to approvals for drugs like pacritinib and momelotinib?

Reshma Rangwala, Chief Medical Officer

Sure. Pacritinib and momelotinib are useful precedents because although their pivotal trials focused on SVR and TSS, pacritinib received accelerated approval based on SVR in a specific population, which highlights the FDA's appreciation for SVR as an important endpoint in myelofibrosis. In momelotinib's case, although the trials focused on SVR and TSS, the FDA demonstrated flexibility and creativity in identifying populations and endpoints that show clear unmet need. I highlight these examples because the FDA is willing to look at the totality of the data beyond the primary endpoints and consider other measures of clinical benefit when making decisions.

Operator, Operator

There are no further questions at this time, Mr. Paulson.

Richard Paulson, President and Chief Executive Officer

Thank you, operator, and thank you again to everyone for joining us today and for your continued interest in Karyopharm. As you've heard, we are very encouraged by the progress we have made across our late-stage programs, and remain very focused and disciplined in our execution to the next stage of important milestones. Most importantly, we remain committed to advancing selinexor's potential to bring meaningful new options to patients with both endometrial cancer and myelofibrosis. We look forward to seeing many of you at ASCO during our oral presentation of our SENTRY results. Thank you for joining us today.

Operator, Operator

Ladies and gentlemen, this does conclude your conference call for today. We thank you very much for your participation, and you may now disconnect. Have a great day, everyone.